2023
Hodges, Sierra | Guler, Seyhmus | Sacca, Valeria | Vangel, Mark | Orr, Scott | Pace-Schott, Edward | Wen, Ya | Ge, Tian | Kong, Jian
In: Sleep Med, vol. 101, pp. 393–400, 2023, ISSN: 1878-5506.
Abstract | Links | BibTeX | Tags:
@article{pmid36516523,
title = {Associations among acute and chronic musculoskeletal pain, sleep duration, and C-reactive protein (CRP): A cross-sectional study of the UK biobank dataset},
author = {Sierra Hodges and Seyhmus Guler and Valeria Sacca and Mark Vangel and Scott Orr and Edward Pace-Schott and Ya Wen and Tian Ge and Jian Kong},
doi = {10.1016/j.sleep.2022.11.013},
issn = {1878-5506},
year = {2023},
date = {2023-01-01},
journal = {Sleep Med},
volume = {101},
pages = {393--400},
abstract = {Both musculoskeletal pain and sleep disturbances are major health problems worldwide. Literature suggests that the two are reciprocally related and both may be associated with changes in C-reactive protein (CRP) levels. However, the relationships among musculoskeletal pain, sleep duration, and CRP remain unclear. In this cross-sectional study, we investigated the relationship between acute and chronic musculoskeletal pain, sleep, and inflammation using the data from the initial visit of the UK Biobank. 17,642 individuals with chronic musculoskeletal pain, 11,962 individuals with acute musculoskeletal pain, and 29,604 pain-free controls were included in the analysis. In addition, we validated the findings using data from the second visit assessment of the UK Biobank. We found that 1) chronic pain was associated with higher CRP levels compared to both acute pain and the pain-free controls; 2) chronic pain was associated with a lower sleep score (a measurement of sleep patterns), compared to acute pain and the pain-free controls; and acute pain was associated with lower sleep scores compared to the controls; 3) there was a significant negative association between the sleep score and CRP; 4) CRP may partially mediate the association between chronic pain and decreased sleep score. However, the effect size of the mediation was rather small, and the pathophysiological significance remains uncertain. Further validation is needed. These findings were partly replicated in the UK Biobank second visit assessment cohort with a smaller sample size. Our findings, which are based on the large UK Biobank dataset, support the interplay between musculoskeletal pain, sleep patterns, and the potential mediating role of CRP on this reciprocal relationship.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Both musculoskeletal pain and sleep disturbances are major health problems worldwide. Literature suggests that the two are reciprocally related and both may be associated with changes in C-reactive protein (CRP) levels. However, the relationships among musculoskeletal pain, sleep duration, and CRP remain unclear. In this cross-sectional study, we investigated the relationship between acute and chronic musculoskeletal pain, sleep, and inflammation using the data from the initial visit of the UK Biobank. 17,642 individuals with chronic musculoskeletal pain, 11,962 individuals with acute musculoskeletal pain, and 29,604 pain-free controls were included in the analysis. In addition, we validated the findings using data from the second visit assessment of the UK Biobank. We found that 1) chronic pain was associated with higher CRP levels compared to both acute pain and the pain-free controls; 2) chronic pain was associated with a lower sleep score (a measurement of sleep patterns), compared to acute pain and the pain-free controls; and acute pain was associated with lower sleep scores compared to the controls; 3) there was a significant negative association between the sleep score and CRP; 4) CRP may partially mediate the association between chronic pain and decreased sleep score. However, the effect size of the mediation was rather small, and the pathophysiological significance remains uncertain. Further validation is needed. These findings were partly replicated in the UK Biobank second visit assessment cohort with a smaller sample size. Our findings, which are based on the large UK Biobank dataset, support the interplay between musculoskeletal pain, sleep patterns, and the potential mediating role of CRP on this reciprocal relationship.
Rapino, Francesca | Natoli, Ted | Limone, Francesco | O'Connor, Erin | Blank, Jack | Tegtmeyer, Matthew | Chen, William | Norabuena, Erika | Narula, Juhi | Hazelbaker, Dane | Angelini, Gabriella | Barrett, Lindy | O'Neil, Alison | Beattie, Ursula K | Thanos, Jessica M | de Rivera, Heather | Sheridan, Steven D | Perlis, Roy H | McCarroll, Steven A | Stevens, Beth | Subramanian, Aravind | Nehme, Ralda | Rubin, Lee L
Small-molecule screen reveals pathways that regulate C4 secretion in stem cell-derived astrocytes Journal Article
In: Stem Cell Reports, vol. 18, no. 1, pp. 237–253, 2023, ISSN: 2213-6711.
Abstract | Links | BibTeX | Tags:
@article{pmid36563689,
title = {Small-molecule screen reveals pathways that regulate C4 secretion in stem cell-derived astrocytes},
author = {Francesca Rapino and Ted Natoli and Francesco Limone and Erin O'Connor and Jack Blank and Matthew Tegtmeyer and William Chen and Erika Norabuena and Juhi Narula and Dane Hazelbaker and Gabriella Angelini and Lindy Barrett and Alison O'Neil and Ursula K Beattie and Jessica M Thanos and Heather de Rivera and Steven D Sheridan and Roy H Perlis and Steven A McCarroll and Beth Stevens and Aravind Subramanian and Ralda Nehme and Lee L Rubin},
doi = {10.1016/j.stemcr.2022.11.018},
issn = {2213-6711},
year = {2023},
date = {2023-01-01},
journal = {Stem Cell Reports},
volume = {18},
number = {1},
pages = {237--253},
abstract = {In the brain, the complement system plays a crucial role in the immune response and in synaptic elimination during normal development and disease. Here, we sought to identify pathways that modulate the production of complement component 4 (C4), recently associated with an increased risk of schizophrenia. To design a disease-relevant assay, we first developed a rapid and robust 3D protocol capable of producing large numbers of astrocytes from pluripotent cells. Transcriptional profiling of these astrocytes confirmed the homogeneity of this population of dorsal fetal-like astrocytes. Using a novel ELISA-based small-molecule screen, we identified epigenetic regulators, as well as inhibitors of intracellular signaling pathways, able to modulate C4 secretion from astrocytes. We then built a connectivity map to predict and validate additional key regulatory pathways, including one involving c-Jun-kinase. This work provides a foundation for developing therapies for CNS diseases involving the complement cascade.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
In the brain, the complement system plays a crucial role in the immune response and in synaptic elimination during normal development and disease. Here, we sought to identify pathways that modulate the production of complement component 4 (C4), recently associated with an increased risk of schizophrenia. To design a disease-relevant assay, we first developed a rapid and robust 3D protocol capable of producing large numbers of astrocytes from pluripotent cells. Transcriptional profiling of these astrocytes confirmed the homogeneity of this population of dorsal fetal-like astrocytes. Using a novel ELISA-based small-molecule screen, we identified epigenetic regulators, as well as inhibitors of intracellular signaling pathways, able to modulate C4 secretion from astrocytes. We then built a connectivity map to predict and validate additional key regulatory pathways, including one involving c-Jun-kinase. This work provides a foundation for developing therapies for CNS diseases involving the complement cascade.
Zekavat, Seyedeh M | Viana-Huete, Vanesa | Matesanz, Nuria | Jorshery, Saman Doroodgar | Zuriaga, María A | Uddin, Md Mesbah | Trinder, Mark | Paruchuri, Kaavya | Zorita, Virginia | Ferrer-Pérez, Alba | Amorós-Pérez, Marta | Kunderfranco, Paolo | Carriero, Roberta | Greco, Carolina M | Aroca-Crevillen, Alejandra | Hidalgo, Andrés | Damrauer, Scott M | Ballantyne, Christie M | Niroula, Abhishek | Gibson, Christopher J | Pirruccello, James | Griffin, Gabriel | Ebert, Benjamin L | Libby, Peter | Fuster, Valentín | Zhao, Hongyu | Ghassemi, Marzyeh | Natarajan, Pradeep | Bick, Alexander G | Fuster, José J | Klarin, Derek
mediated clonal hematopoiesis confers increased risk for incident atherosclerotic disease Journal Article
In: Nat Cardiovasc Res, vol. 2, pp. 144–158, 2023, ISSN: 2731-0590.
Abstract | Links | BibTeX | Tags:
@article{pmid36949957,
title = {mediated clonal hematopoiesis confers increased risk for incident atherosclerotic disease},
author = {Seyedeh M Zekavat and Vanesa Viana-Huete and Nuria Matesanz and Saman Doroodgar Jorshery and María A Zuriaga and Md Mesbah Uddin and Mark Trinder and Kaavya Paruchuri and Virginia Zorita and Alba Ferrer-Pérez and Marta Amorós-Pérez and Paolo Kunderfranco and Roberta Carriero and Carolina M Greco and Alejandra Aroca-Crevillen and Andrés Hidalgo and Scott M Damrauer and Christie M Ballantyne and Abhishek Niroula and Christopher J Gibson and James Pirruccello and Gabriel Griffin and Benjamin L Ebert and Peter Libby and Valentín Fuster and Hongyu Zhao and Marzyeh Ghassemi and Pradeep Natarajan and Alexander G Bick and José J Fuster and Derek Klarin},
doi = {10.1038/s44161-022-00206-6},
issn = {2731-0590},
year = {2023},
date = {2023-01-01},
journal = {Nat Cardiovasc Res},
volume = {2},
pages = {144--158},
abstract = {Somatic mutations in blood indicative of clonal hematopoiesis of indeterminate potential (CHIP) are associated with an increased risk of hematologic malignancy, coronary artery disease, and all-cause mortality. Here we analyze the relation between CHIP status and incident peripheral artery disease (PAD) and atherosclerosis, using whole-exome sequencing and clinical data from the UK Biobank and Mass General Brigham Biobank. CHIP associated with incident PAD and atherosclerotic disease across multiple beds, with increased risk among individuals with CHIP driven by mutation in DNA Damage Repair (DDR) genes such as and . To model the effects of DDR-induced CHIP on atherosclerosis, we used a competitive bone marrow transplantation strategy, and generated atherosclerosis-prone -/- chimeric mice carrying 20% p53-deficient hematopoietic cells. The chimeric mice were analyzed 13-weeks post-grafting and showed increased aortic plaque size and accumulation of macrophages within the plaque, driven by increased proliferation of p53-deficient plaque macrophages. In summary, our findings highlight the role of CHIP as a broad driver of atherosclerosis across the entire arterial system beyond the coronary arteries, and provide genetic and experimental support for a direct causal contribution of TP53-mutant CHIP to atherosclerosis.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Somatic mutations in blood indicative of clonal hematopoiesis of indeterminate potential (CHIP) are associated with an increased risk of hematologic malignancy, coronary artery disease, and all-cause mortality. Here we analyze the relation between CHIP status and incident peripheral artery disease (PAD) and atherosclerosis, using whole-exome sequencing and clinical data from the UK Biobank and Mass General Brigham Biobank. CHIP associated with incident PAD and atherosclerotic disease across multiple beds, with increased risk among individuals with CHIP driven by mutation in DNA Damage Repair (DDR) genes such as and . To model the effects of DDR-induced CHIP on atherosclerosis, we used a competitive bone marrow transplantation strategy, and generated atherosclerosis-prone -/- chimeric mice carrying 20% p53-deficient hematopoietic cells. The chimeric mice were analyzed 13-weeks post-grafting and showed increased aortic plaque size and accumulation of macrophages within the plaque, driven by increased proliferation of p53-deficient plaque macrophages. In summary, our findings highlight the role of CHIP as a broad driver of atherosclerosis across the entire arterial system beyond the coronary arteries, and provide genetic and experimental support for a direct causal contribution of TP53-mutant CHIP to atherosclerosis.
Yu, Dongmei | Scharf, Jeremiah M
Direct and Indirect Effects in Trio Studies: You Don't Know What You're Missing Journal Article
In: Biol Psychiatry, vol. 93, no. 1, pp. 6–7, 2023, ISSN: 1873-2402.
Abstract | Links | BibTeX | Tags:
@article{pmid36456078,
title = {Direct and Indirect Effects in Trio Studies: You Don't Know What You're Missing},
author = {Dongmei Yu and Jeremiah M Scharf},
doi = {10.1016/j.biopsych.2022.10.004},
issn = {1873-2402},
year = {2023},
date = {2023-01-01},
urldate = {2023-01-01},
journal = {Biol Psychiatry},
volume = {93},
number = {1},
pages = {6--7},
abstract = {Direct and Indirect Effects in Trio Studies: You Don't Know What You're Missing},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Direct and Indirect Effects in Trio Studies: You Don't Know What You're Missing
Moorthy, Tiahna | Nguyen, Huyen | Chen, Ying | Austin, Jehannine | Smoller, Jordan W | Hercher, Laura | Sabatello, Maya
How do experts in psychiatric genetics view the clinical utility of polygenic risk scores for schizophrenia? Journal Article
In: Am J Med Genet B Neuropsychiatr Genet, vol. 192, no. 7-8, pp. 161–170, 2023, ISSN: 1552-485X.
Abstract | Links | BibTeX | Tags:
@article{pmid37158703,
title = {How do experts in psychiatric genetics view the clinical utility of polygenic risk scores for schizophrenia?},
author = {Tiahna Moorthy and Huyen Nguyen and Ying Chen and Jehannine Austin and Jordan W Smoller and Laura Hercher and Maya Sabatello},
doi = {10.1002/ajmg.b.32939},
issn = {1552-485X},
year = {2023},
date = {2023-01-01},
journal = {Am J Med Genet B Neuropsychiatr Genet},
volume = {192},
number = {7-8},
pages = {161--170},
abstract = {Polygenic risk scores (PRS) are promising for identifying common variant-related inheritance for psychiatric conditions but their integration into clinical practice depends on their clinical utility and psychiatrists' understanding of PRS. Our online survey explored these issues with 276 professionals working in psychiatric genetics (RR: 19%). Overall, participants demonstrated knowledge of how to interpret PRS results. Their performance on knowledge-based questions was positively correlated with participants' self-reported familiarity with PRS (r = 0.21, p = 0.0006) although differences were not statistically significant (Wald Chi-square = 3.29, df = 1, p = 0.07). However, only 48.9% of all participants answered all knowledge questions correctly. Many participants (56.5%), especially researchers (42%), indicated having at least occasional conversations about the role of genetics in psychiatric conditions with patients and/or family members. Most participants (62.7%) indicated that PRS are not yet sufficiently robust for assessment of susceptibility to schizophrenia; most significant obstacles were low predictive power and lack of population diversity in available PRS (selected, respectively, by 53.6% and 29.3% of participants). Nevertheless, 89.8% of participants were optimistic about the use of PRS in the next 10 years, suggesting a belief that current shortcomings could be addressed. Our findings inform about the perceptions of psychiatric professionals regarding PRS and the application of PRS in psychiatry.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Polygenic risk scores (PRS) are promising for identifying common variant-related inheritance for psychiatric conditions but their integration into clinical practice depends on their clinical utility and psychiatrists' understanding of PRS. Our online survey explored these issues with 276 professionals working in psychiatric genetics (RR: 19%). Overall, participants demonstrated knowledge of how to interpret PRS results. Their performance on knowledge-based questions was positively correlated with participants' self-reported familiarity with PRS (r = 0.21, p = 0.0006) although differences were not statistically significant (Wald Chi-square = 3.29, df = 1, p = 0.07). However, only 48.9% of all participants answered all knowledge questions correctly. Many participants (56.5%), especially researchers (42%), indicated having at least occasional conversations about the role of genetics in psychiatric conditions with patients and/or family members. Most participants (62.7%) indicated that PRS are not yet sufficiently robust for assessment of susceptibility to schizophrenia; most significant obstacles were low predictive power and lack of population diversity in available PRS (selected, respectively, by 53.6% and 29.3% of participants). Nevertheless, 89.8% of participants were optimistic about the use of PRS in the next 10 years, suggesting a belief that current shortcomings could be addressed. Our findings inform about the perceptions of psychiatric professionals regarding PRS and the application of PRS in psychiatry.
Sheu, Yi-Han | Magdamo, Colin | Miller, Matthew | Smoller, Jordan W | Blacker, Deborah
Initial antidepressant choice by non-psychiatrists: Learning from large-scale electronic health records Journal Article
In: Gen Hosp Psychiatry, vol. 81, pp. 22–31, 2023, ISSN: 1873-7714.
Abstract | Links | BibTeX | Tags:
@article{pmid36724694,
title = {Initial antidepressant choice by non-psychiatrists: Learning from large-scale electronic health records},
author = {Yi-Han Sheu and Colin Magdamo and Matthew Miller and Jordan W Smoller and Deborah Blacker},
doi = {10.1016/j.genhosppsych.2022.12.004},
issn = {1873-7714},
year = {2023},
date = {2023-01-01},
journal = {Gen Hosp Psychiatry},
volume = {81},
pages = {22--31},
abstract = {OBJECTIVES: Pharmacological treatment of depression mostly occurs in non-psychiatric settings, but the determinants of initial choice of antidepressant treatment in these settings are unclear. We investigate how non-psychiatrists choose among four antidepressant classes at first prescription (selective serotonin reuptake inhibitors [SSRI], bupropion, mirtazapine, or serotonin-norepinephrine reuptake inhibitors [SNRI]).nnMETHOD: Using electronic health records (EHRs), we included adult patients at the time of first antidepressant prescription with a co-occurring diagnosis code for a depressive disorder. We selected 64 variables based on a literature search and expert consultation, constructed the variables from either structured codes or through applying natural language processing (NLP), and modeled antidepressant choice using multinomial logistic regression, using SSRI as the reference class.nnRESULTS: With 47,528 patients, we observed significant associations for 36 of 64 variables. Many of these associations suggested antidepressants' known pharmacological properties/actions guided choice. For example, there was a decreased likelihood of bupropion prescription among patients with epilepsy (adjusted OR 0.49, 95%CI: 0.41-0.57, p < 0.001), and an increased likelihood of mirtazapine prescription among patients with insomnia (adjusted OR 1.59, 95%CI: 1.40-1.80, p < 0.001).nnCONCLUSIONS: Broadly speaking, non-psychiatrists' selection of antidepressant class appears to be at least in part guided by clinically relevant pharmacological considerations.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
OBJECTIVES: Pharmacological treatment of depression mostly occurs in non-psychiatric settings, but the determinants of initial choice of antidepressant treatment in these settings are unclear. We investigate how non-psychiatrists choose among four antidepressant classes at first prescription (selective serotonin reuptake inhibitors [SSRI], bupropion, mirtazapine, or serotonin-norepinephrine reuptake inhibitors [SNRI]).nnMETHOD: Using electronic health records (EHRs), we included adult patients at the time of first antidepressant prescription with a co-occurring diagnosis code for a depressive disorder. We selected 64 variables based on a literature search and expert consultation, constructed the variables from either structured codes or through applying natural language processing (NLP), and modeled antidepressant choice using multinomial logistic regression, using SSRI as the reference class.nnRESULTS: With 47,528 patients, we observed significant associations for 36 of 64 variables. Many of these associations suggested antidepressants' known pharmacological properties/actions guided choice. For example, there was a decreased likelihood of bupropion prescription among patients with epilepsy (adjusted OR 0.49, 95%CI: 0.41-0.57, p < 0.001), and an increased likelihood of mirtazapine prescription among patients with insomnia (adjusted OR 1.59, 95%CI: 1.40-1.80, p < 0.001).nnCONCLUSIONS: Broadly speaking, non-psychiatrists' selection of antidepressant class appears to be at least in part guided by clinically relevant pharmacological considerations.
Gupta, Rahul | Kanai, Masahiro | Durham, Timothy J | Tsuo, Kristin | McCoy, Jason G | Chinnery, Patrick F | Karczewski, Konrad J | Calvo, Sarah E | Neale, Benjamin M | Mootha, Vamsi K
Nuclear genetic control of mtDNA copy number and heteroplasmy in humans Miscellaneous
2023.
Abstract | Links | BibTeX | Tags:
@misc{pmid36711677,
title = {Nuclear genetic control of mtDNA copy number and heteroplasmy in humans},
author = {Rahul Gupta and Masahiro Kanai and Timothy J Durham and Kristin Tsuo and Jason G McCoy and Patrick F Chinnery and Konrad J Karczewski and Sarah E Calvo and Benjamin M Neale and Vamsi K Mootha},
doi = {10.1101/2023.01.19.23284696},
year = {2023},
date = {2023-01-01},
journal = {medRxiv},
abstract = {Human mitochondria contain a high copy number, maternally transmitted genome (mtDNA) that encodes 13 proteins required for oxidative phosphorylation. Heteroplasmy arises when multiple mtDNA variants co-exist in an individual and can exhibit complex dynamics in disease and in aging. As all proteins involved in mtDNA replication and maintenance are nuclear-encoded, heteroplasmy levels can, in principle, be under nuclear genetic control, however this has never been shown in humans. Here, we develop algorithms to quantify mtDNA copy number (mtCN) and heteroplasmy levels using blood-derived whole genome sequences from 274,832 individuals of diverse ancestry and perform GWAS to identify nuclear loci controlling these traits. After careful correction for blood cell composition, we observe that mtCN declines linearly with age and is associated with 92 independent nuclear genetic loci. We find that nearly every individual carries heteroplasmic variants that obey two key patterns: (1) heteroplasmic single nucleotide variants are somatic mutations that accumulate sharply after age 70, while (2) heteroplasmic indels are maternally transmitted as mtDNA mixtures with resulting levels influenced by 42 independent nuclear loci involved in mtDNA replication, maintenance, and novel pathways. These nuclear loci do not appear to act by mtDNA mutagenesis, but rather, likely act by conferring a replicative advantage to specific mtDNA molecules. As an illustrative example, the most common heteroplasmy we identify is a length variant carried by >50% of humans at position m.302 within a G-quadruplex known to serve as a replication switch. We find that this heteroplasmic variant exerts -acting genetic control over mtDNA abundance and is itself under -acting genetic control of nuclear loci encoding protein components of this regulatory switch. Our study showcases how nuclear haplotype can privilege the replication of specific mtDNA molecules to shape mtCN and heteroplasmy dynamics in the human population.},
keywords = {},
pubstate = {published},
tppubtype = {misc}
}
Human mitochondria contain a high copy number, maternally transmitted genome (mtDNA) that encodes 13 proteins required for oxidative phosphorylation. Heteroplasmy arises when multiple mtDNA variants co-exist in an individual and can exhibit complex dynamics in disease and in aging. As all proteins involved in mtDNA replication and maintenance are nuclear-encoded, heteroplasmy levels can, in principle, be under nuclear genetic control, however this has never been shown in humans. Here, we develop algorithms to quantify mtDNA copy number (mtCN) and heteroplasmy levels using blood-derived whole genome sequences from 274,832 individuals of diverse ancestry and perform GWAS to identify nuclear loci controlling these traits. After careful correction for blood cell composition, we observe that mtCN declines linearly with age and is associated with 92 independent nuclear genetic loci. We find that nearly every individual carries heteroplasmic variants that obey two key patterns: (1) heteroplasmic single nucleotide variants are somatic mutations that accumulate sharply after age 70, while (2) heteroplasmic indels are maternally transmitted as mtDNA mixtures with resulting levels influenced by 42 independent nuclear loci involved in mtDNA replication, maintenance, and novel pathways. These nuclear loci do not appear to act by mtDNA mutagenesis, but rather, likely act by conferring a replicative advantage to specific mtDNA molecules. As an illustrative example, the most common heteroplasmy we identify is a length variant carried by >50% of humans at position m.302 within a G-quadruplex known to serve as a replication switch. We find that this heteroplasmic variant exerts -acting genetic control over mtDNA abundance and is itself under -acting genetic control of nuclear loci encoding protein components of this regulatory switch. Our study showcases how nuclear haplotype can privilege the replication of specific mtDNA molecules to shape mtCN and heteroplasmy dynamics in the human population.
Chen, Yutong | Mayerhofer, Ernst | Parodi, Livia | Harloff, Andreas | Batra, Puneet | Rosand, Jonathan | Anderson, Christopher D
Beyond the Limits of Visual Learning: Prediction of Time From Onset From Noncontrast CT of Acute Ischemic Stroke Miscellaneous
2023, ISSN: 1524-4628.
@misc{pmid36475469,
title = {Beyond the Limits of Visual Learning: Prediction of Time From Onset From Noncontrast CT of Acute Ischemic Stroke},
author = {Yutong Chen and Ernst Mayerhofer and Livia Parodi and Andreas Harloff and Puneet Batra and Jonathan Rosand and Christopher D Anderson},
doi = {10.1161/STROKEAHA.122.041370},
issn = {1524-4628},
year = {2023},
date = {2023-01-01},
urldate = {2023-01-01},
journal = {Stroke},
volume = {54},
number = {1},
pages = {e7--e8},
keywords = {},
pubstate = {published},
tppubtype = {misc}
}
Pollastri, Alisha R | Forchelli, Gina | Vuijk, Pieter J | Stoll, Samantha J | Capawana, Michael R | Bellitti, Joseph | Braaten, Ellen B | Doyle, Alysa E
Behavior ratings of executive functions index multiple domains of psychopathology and school functioning in child psychiatric outpatients Journal Article
In: Appl Neuropsychol Child, vol. 12, no. 4, pp. 304–317, 2023, ISSN: 2162-2973.
Abstract | Links | BibTeX | Tags:
@article{pmid35900144,
title = {Behavior ratings of executive functions index multiple domains of psychopathology and school functioning in child psychiatric outpatients},
author = {Alisha R Pollastri and Gina Forchelli and Pieter J Vuijk and Samantha J Stoll and Michael R Capawana and Joseph Bellitti and Ellen B Braaten and Alysa E Doyle},
doi = {10.1080/21622965.2022.2099743},
issn = {2162-2973},
year = {2023},
date = {2023-01-01},
journal = {Appl Neuropsychol Child},
volume = {12},
number = {4},
pages = {304--317},
abstract = {Behavior rating scales of executive functions (EFs) are convenient and associate with academic and other outcomes; however, prior studies indicate limited correlations with psychometric tests of EFs. To better understand their potential for clinical utility, we examined the extent to which parent ratings on the Behavior Rating Inventory of Executive Function (BRIEF) related to psychopathology constructs and psychometric test scores in a sample of = 692 psychiatric outpatients aged 8-17. Then, in a subsample of the youth ( = 261), we related the BRIEF, psychopathology constructs, and psychometric test scores to teacher ratings of school functioning. BRIEF scales were significantly associated with multiple types of psychopathology including ADHD, autism spectrum, mood, anxiety, conduct, oppositional defiant, and psychotic disorders. While the BRIEF showed limited associations with psychometric EF tests, its Global Executive Composite score explained additional variance in teacher-reported functioning beyond what was predicted by clinical diagnoses (additional explained variance of 9.9% in study skills) and psychometric tests (additional explained variance of 2.1% in learning problems and 4.5% in study skills). The Global Executive Composite was not significantly related to teacher-rated school functioning after psychiatric symptoms were accounted for. These findings support further investigation of the unique contribution of the BRIEF in clinical practice.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Behavior rating scales of executive functions (EFs) are convenient and associate with academic and other outcomes; however, prior studies indicate limited correlations with psychometric tests of EFs. To better understand their potential for clinical utility, we examined the extent to which parent ratings on the Behavior Rating Inventory of Executive Function (BRIEF) related to psychopathology constructs and psychometric test scores in a sample of = 692 psychiatric outpatients aged 8-17. Then, in a subsample of the youth ( = 261), we related the BRIEF, psychopathology constructs, and psychometric test scores to teacher ratings of school functioning. BRIEF scales were significantly associated with multiple types of psychopathology including ADHD, autism spectrum, mood, anxiety, conduct, oppositional defiant, and psychotic disorders. While the BRIEF showed limited associations with psychometric EF tests, its Global Executive Composite score explained additional variance in teacher-reported functioning beyond what was predicted by clinical diagnoses (additional explained variance of 9.9% in study skills) and psychometric tests (additional explained variance of 2.1% in learning problems and 4.5% in study skills). The Global Executive Composite was not significantly related to teacher-rated school functioning after psychiatric symptoms were accounted for. These findings support further investigation of the unique contribution of the BRIEF in clinical practice.
Cole, Joanne B | Westerman, Kenneth E | Manning, Alisa K | Florez, Jose C | Hirschhorn, Joel N
2023, ISSN: 1664-8021.
Abstract | Links | BibTeX | Tags:
@misc{pmid37214416,
title = {Corrigendum: Genetic heritability as a tool to evaluate the precision of 24-hour recall dietary questionnaire variables in UK Biobank},
author = {Joanne B Cole and Kenneth E Westerman and Alisa K Manning and Jose C Florez and Joel N Hirschhorn},
doi = {10.3389/fgene.2023.1202158},
issn = {1664-8021},
year = {2023},
date = {2023-01-01},
journal = {Front Genet},
volume = {14},
pages = {1202158},
abstract = {[This corrects the article DOI: 10.3389/fgene.2022.1070511.].},
keywords = {},
pubstate = {published},
tppubtype = {misc}
}
[This corrects the article DOI: 10.3389/fgene.2022.1070511.].
Chaisinanunkul, Napasri | Khurshid, Shaan | Buck, Brian H | Rabinstein, Alejandro A | Anderson, Christopher D | Hill, Michael D | Fugate, Jennifer E | Saver, Jeffrey L
Corrigendum: How often is occult atrial fibrillation in cryptogenic stroke causal vs. incidental? A meta-analysis Miscellaneous
2023, ISSN: 1664-2295.
Abstract | Links | BibTeX | Tags:
@misc{pmid37234786,
title = {Corrigendum: How often is occult atrial fibrillation in cryptogenic stroke causal vs. incidental? A meta-analysis},
author = {Napasri Chaisinanunkul and Shaan Khurshid and Brian H Buck and Alejandro A Rabinstein and Christopher D Anderson and Michael D Hill and Jennifer E Fugate and Jeffrey L Saver},
doi = {10.3389/fneur.2023.1206563},
issn = {1664-2295},
year = {2023},
date = {2023-01-01},
journal = {Front Neurol},
volume = {14},
pages = {1206563},
abstract = {[This corrects the article DOI: 10.3389/fneur.2023.1103664.].},
keywords = {},
pubstate = {published},
tppubtype = {misc}
}
[This corrects the article DOI: 10.3389/fneur.2023.1103664.].
Vlasschaert, Caitlyn | Heimlich, J Brett | Rauh, Michael J | Natarajan, Pradeep | Bick, Alexander G
Interleukin-6 Receptor Polymorphism Attenuates Clonal Hematopoiesis-Mediated Coronary Artery Disease Risk Among 451 180 Individuals in the UK Biobank Miscellaneous
2023, ISSN: 1524-4539.
@misc{pmid36689568,
title = {Interleukin-6 Receptor Polymorphism Attenuates Clonal Hematopoiesis-Mediated Coronary Artery Disease Risk Among 451 180 Individuals in the UK Biobank},
author = {Caitlyn Vlasschaert and J Brett Heimlich and Michael J Rauh and Pradeep Natarajan and Alexander G Bick},
doi = {10.1161/CIRCULATIONAHA.122.062126},
issn = {1524-4539},
year = {2023},
date = {2023-01-01},
journal = {Circulation},
volume = {147},
number = {4},
pages = {358--360},
keywords = {},
pubstate = {published},
tppubtype = {misc}
}
Noel, Maxence | Chasman, Daniel I | Mora, Samia | Otvos, James D | Palmer, Christopher D | Parsons, Patrick J | Smoller, Jordan W | Cummings, Richard D | Mealer, Robert G
The Inflammation Biomarker GlycA Reflects Plasma N-Glycan Branching Journal Article
In: Clin Chem, vol. 69, no. 1, pp. 80–87, 2023, ISSN: 1530-8561.
Abstract | Links | BibTeX | Tags:
@article{pmid36254612,
title = {The Inflammation Biomarker GlycA Reflects Plasma N-Glycan Branching},
author = {Maxence Noel and Daniel I Chasman and Samia Mora and James D Otvos and Christopher D Palmer and Patrick J Parsons and Jordan W Smoller and Richard D Cummings and Robert G Mealer},
doi = {10.1093/clinchem/hvac160},
issn = {1530-8561},
year = {2023},
date = {2023-01-01},
journal = {Clin Chem},
volume = {69},
number = {1},
pages = {80--87},
abstract = {BACKGROUND: GlycA is a nuclear magnetic resonance (NMR) signal in plasma that correlates with inflammation and cardiovascular outcomes in large data sets. The signal is thought to originate from N-acetylglucosamine (GlcNAc) residues of branched plasma N-glycans, though direct experimental evidence is limited. Trace element concentrations affect plasma glycosylation patterns and may thereby also influence GlycA.nnMETHODS: NMR GlycA signal was measured in plasma samples from 87 individuals and correlated with MALDI-MS N-glycomics and trace element analysis. We further evaluated the genetic association with GlycA at rs13107325, a single nucleotide polymorphism resulting in a missense variant within SLC39A8, a manganese transporter that influences N-glycan branching, both in our samples and existing genome-wide association studies data from 22 835 participants in the Women's Health Study (WHS).nnRESULTS: GlycA signal was correlated with both N-glycan branching (r2 ranging from 0.125-0.265; all P < 0.001) and copper concentration (r2 = 0.348, P < 0.0001). In addition, GlycA levels were associated with rs13107325 genotype in the WHS (β [standard error of the mean] = -4.66 [1.2674], P = 0.0002).nnCONCLUSIONS: These results provide the first direct experimental evidence linking the GlycA NMR signal to N-glycan branching commonly associated with acute phase reactive proteins involved in inflammation.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
BACKGROUND: GlycA is a nuclear magnetic resonance (NMR) signal in plasma that correlates with inflammation and cardiovascular outcomes in large data sets. The signal is thought to originate from N-acetylglucosamine (GlcNAc) residues of branched plasma N-glycans, though direct experimental evidence is limited. Trace element concentrations affect plasma glycosylation patterns and may thereby also influence GlycA.nnMETHODS: NMR GlycA signal was measured in plasma samples from 87 individuals and correlated with MALDI-MS N-glycomics and trace element analysis. We further evaluated the genetic association with GlycA at rs13107325, a single nucleotide polymorphism resulting in a missense variant within SLC39A8, a manganese transporter that influences N-glycan branching, both in our samples and existing genome-wide association studies data from 22 835 participants in the Women's Health Study (WHS).nnRESULTS: GlycA signal was correlated with both N-glycan branching (r2 ranging from 0.125-0.265; all P < 0.001) and copper concentration (r2 = 0.348, P < 0.0001). In addition, GlycA levels were associated with rs13107325 genotype in the WHS (β [standard error of the mean] = -4.66 [1.2674], P = 0.0002).nnCONCLUSIONS: These results provide the first direct experimental evidence linking the GlycA NMR signal to N-glycan branching commonly associated with acute phase reactive proteins involved in inflammation.
Brunoni, André Russowsky | Suen, Paulo Jeng Chian | Bacchi, Pedro Starzynski | Razza, Lais Boralli | Klein, Izio | Santos, Leonardo Afonso Dos | de Souza Santos, Itamar | da Costa Lane Valiengo, Leandro | Gallucci-Neto, José | Moreno, Marina Lopes | Pinto, Bianca Silva | de Cássia Silva Félix, Larissa | de Sousa, Juliana Pereira | Viana, Maria Carmen | Forte, Pamela Marques | de Altisent Oliveira Cardoso, Marcia Cristina | Bittencourt, Marcio Sommer | Pelosof, Rebeca | de Siqueira, Luciana Lima | Fatori, Daniel | Bellini, Helena | Bueno, Priscila Vilela Silveira | Passos, Ives Cavalcante | Nunes, Maria Angelica | Salum, Giovanni Abrahão | Bauermeister, Sarah | Smoller, Jordan W | Lotufo, Paulo Andrade | Benseñor, Isabela Martins
In: Psychol Med, vol. 53, no. 2, pp. 446–457, 2023, ISSN: 1469-8978.
Abstract | Links | BibTeX | Tags:
@article{pmid33880984,
title = {Prevalence and risk factors of psychiatric symptoms and diagnoses before and during the COVID-19 pandemic: findings from the ELSA-Brasil COVID-19 mental health cohort},
author = {André Russowsky Brunoni and Paulo Jeng Chian Suen and Pedro Starzynski Bacchi and Lais Boralli Razza and Izio Klein and Leonardo Afonso Dos Santos and Itamar de Souza Santos and Leandro da Costa Lane Valiengo and José Gallucci-Neto and Marina Lopes Moreno and Bianca Silva Pinto and Larissa de Cássia Silva Félix and Juliana Pereira de Sousa and Maria Carmen Viana and Pamela Marques Forte and Marcia Cristina de Altisent Oliveira Cardoso and Marcio Sommer Bittencourt and Rebeca Pelosof and Luciana Lima de Siqueira and Daniel Fatori and Helena Bellini and Priscila Vilela Silveira Bueno and Ives Cavalcante Passos and Maria Angelica Nunes and Giovanni Abrahão Salum and Sarah Bauermeister and Jordan W Smoller and Paulo Andrade Lotufo and Isabela Martins Benseñor},
doi = {10.1017/S0033291721001719},
issn = {1469-8978},
year = {2023},
date = {2023-01-01},
journal = {Psychol Med},
volume = {53},
number = {2},
pages = {446--457},
abstract = {BACKGROUND: There is mixed evidence on increasing rates of psychiatric disorders and symptoms during the coronavirus disease 2019 (COVID-19) pandemic in 2020. We evaluated pandemic-related psychopathology and psychiatry diagnoses and their determinants in the Brazilian Longitudinal Study of Health (ELSA-Brasil) São Paulo Research Center.nnMETHODS: Between pre-pandemic ELSA-Brasil assessments in 2008-2010 (wave-1), 2012-2014 (wave-2), 2016-2018 (wave-3) and three pandemic assessments in 2020 (COVID-19 waves in May-July, July-September, and October-December), rates of common psychiatric symptoms, and depressive, anxiety, and common mental disorders (CMDs) were compared using the Clinical Interview Scheduled-Revised (CIS-R) and the Depression Anxiety Stress Scale-21 (DASS-21). Multivariable generalized linear models, adjusted by age, gender, educational level, and ethnicity identified variables associated with an elevated risk for mental disorders.nnRESULTS: In 2117 participants (mean age 62.3 years, 58.2% females), rates of CMDs and depressive disorders did not significantly change over time, oscillating from 23.5% to 21.1%, and 3.3% to 2.8%, respectively; whereas rate of anxiety disorders significantly decreased (2008-2010: 13.8%; 2016-2018: 9.8%; 2020: 8%). There was a decrease along three wave-COVID assessments for depression [ = -0.37, 99.5% confidence interval (CI) -0.50 to -0.23], anxiety ( = -0.37, 99.5% CI -0.48 to -0.26), and stress ( = -0.48, 99.5% CI -0.64 to -0.33) symptoms (all s < 0.001). Younger age, female sex, lower educational level, non-white ethnicity, and previous psychiatric disorders were associated with increased odds for psychiatric disorders, whereas self-evaluated good health and good quality of relationships with decreased risk.nnCONCLUSION: No consistent evidence of pandemic-related worsening psychopathology in our cohort was found. Indeed, psychiatric symptoms slightly decreased along 2020. Risk factors representing socioeconomic disadvantages were associated with increased odds of psychiatric disorders.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
BACKGROUND: There is mixed evidence on increasing rates of psychiatric disorders and symptoms during the coronavirus disease 2019 (COVID-19) pandemic in 2020. We evaluated pandemic-related psychopathology and psychiatry diagnoses and their determinants in the Brazilian Longitudinal Study of Health (ELSA-Brasil) São Paulo Research Center.nnMETHODS: Between pre-pandemic ELSA-Brasil assessments in 2008-2010 (wave-1), 2012-2014 (wave-2), 2016-2018 (wave-3) and three pandemic assessments in 2020 (COVID-19 waves in May-July, July-September, and October-December), rates of common psychiatric symptoms, and depressive, anxiety, and common mental disorders (CMDs) were compared using the Clinical Interview Scheduled-Revised (CIS-R) and the Depression Anxiety Stress Scale-21 (DASS-21). Multivariable generalized linear models, adjusted by age, gender, educational level, and ethnicity identified variables associated with an elevated risk for mental disorders.nnRESULTS: In 2117 participants (mean age 62.3 years, 58.2% females), rates of CMDs and depressive disorders did not significantly change over time, oscillating from 23.5% to 21.1%, and 3.3% to 2.8%, respectively; whereas rate of anxiety disorders significantly decreased (2008-2010: 13.8%; 2016-2018: 9.8%; 2020: 8%). There was a decrease along three wave-COVID assessments for depression [ = -0.37, 99.5% confidence interval (CI) -0.50 to -0.23], anxiety ( = -0.37, 99.5% CI -0.48 to -0.26), and stress ( = -0.48, 99.5% CI -0.64 to -0.33) symptoms (all s < 0.001). Younger age, female sex, lower educational level, non-white ethnicity, and previous psychiatric disorders were associated with increased odds for psychiatric disorders, whereas self-evaluated good health and good quality of relationships with decreased risk.nnCONCLUSION: No consistent evidence of pandemic-related worsening psychopathology in our cohort was found. Indeed, psychiatric symptoms slightly decreased along 2020. Risk factors representing socioeconomic disadvantages were associated with increased odds of psychiatric disorders.
Fernández-Rhodes, Lindsay | Graff, Mariaelisa | Buchanan, Victoria L | Justice, Anne E | Highland, Heather M | Guo, Xiuqing | Zhu, Wanying | Chen, Hung-Hsin | Young, Kristin L | Adhikari, Kaustubh | Palmer, Nicholette D | Below, Jennifer E | Bradfield, Jonathan | Pereira, Alexandre C | Glover, LáShauntá | Kim, Daeeun | Lilly, Adam G | Shrestha, Poojan | Thomas, Alvin G | Zhang, Xinruo | Chen, Minhui | Chiang, Charleston W K | Pulit, Sara | Horimoto, Andrea | Krieger, Jose E | Guindo-Martínez, Marta | Preuss, Michael | Schumann, Claudia | Smit, Roelof A J | Torres-Mejía, Gabriela | Acuña-Alonzo, Victor | Bedoya, Gabriel | Bortolini, Maria-Cátira | Canizales-Quinteros, Samuel | Gallo, Carla | González-José, Rolando | Poletti, Giovanni | Rothhammer, Francisco | Hakonarson, Hakon | Igo, Robert | Adler, Sharon G | Iyengar, Sudha K | Nicholas, Susanne B | Gogarten, Stephanie M | Isasi, Carmen R | Papnicolaou, George | Stilp, Adrienne M | Qi, Qibin | Kho, Minjung | Smith, Jennifer A | Langefeld, Carl D | Wagenknecht, Lynne | Mckean-Cowdin, Roberta | Gao, Xiaoyi Raymond | Nousome, Darryl | Conti, David V | Feng, Ye | Allison, Matthew A | Arzumanyan, Zorayr | Buchanan, Thomas A | Chen, Yii-Der Ida | Genter, Pauline M | Goodarzi, Mark O | Hai, Yang | Hsueh, Willa | Ipp, Eli | Kandeel, Fouad R | Lam, Kelvin | Li, Xiaohui | Nadler, Jerry L | Raffel, Leslie J | Roll, Kathryn | Sandow, Kevin | Tan, Jingyi | Taylor, Kent D | Xiang, Anny H | Yao, Jie | Audirac-Chalifour, Astride | de Jesus Peralta Romero, Jose | Hartwig, Fernando | Horta, Bernando | Blangero, John | Curran, Joanne E | Duggirala, Ravindranath | Lehman, Donna E | Puppala, Sobha | Fejerman, Laura | John, Esther M | Aguilar-Salinas, Carlos | Burtt, Noël P | Florez, Jose C | García-Ortíz, Humberto | González-Villalpando, Clicerio | Mercader, Josep | Orozco, Lorena | Tusié-Luna, Teresa | Blanco, Estela | Gahagan, Sheila | Cox, Nancy J | Hanis, Craig | Butte, Nancy F | Cole, Shelley A | Comuzzie, Anthony G | Voruganti, V Saroja | Rohde, Rebecca | Wang, Yujie | Sofer, Tamar | Ziv, Elad | Grant, Struan F A | Ruiz-Linares, Andres | Rotter, Jerome I | Haiman, Christopher A | Parra, Esteban J | Cruz, Miguel | Loos, Ruth J F | North, Kari E
2023, ISSN: 2666-2477.
Abstract | Links | BibTeX | Tags:
@misc{pmid36268164,
title = {Erratum: Ancestral diversity improves discovery and fine-mapping of genetic loci for anthropometric traits-The Hispanic/Latino Anthropometry Consortium},
author = {Lindsay Fernández-Rhodes and Mariaelisa Graff and Victoria L Buchanan and Anne E Justice and Heather M Highland and Xiuqing Guo and Wanying Zhu and Hung-Hsin Chen and Kristin L Young and Kaustubh Adhikari and Nicholette D Palmer and Jennifer E Below and Jonathan Bradfield and Alexandre C Pereira and LáShauntá Glover and Daeeun Kim and Adam G Lilly and Poojan Shrestha and Alvin G Thomas and Xinruo Zhang and Minhui Chen and Charleston W K Chiang and Sara Pulit and Andrea Horimoto and Jose E Krieger and Marta Guindo-Martínez and Michael Preuss and Claudia Schumann and Roelof A J Smit and Gabriela Torres-Mejía and Victor Acuña-Alonzo and Gabriel Bedoya and Maria-Cátira Bortolini and Samuel Canizales-Quinteros and Carla Gallo and Rolando González-José and Giovanni Poletti and Francisco Rothhammer and Hakon Hakonarson and Robert Igo and Sharon G Adler and Sudha K Iyengar and Susanne B Nicholas and Stephanie M Gogarten and Carmen R Isasi and George Papnicolaou and Adrienne M Stilp and Qibin Qi and Minjung Kho and Jennifer A Smith and Carl D Langefeld and Lynne Wagenknecht and Roberta Mckean-Cowdin and Xiaoyi Raymond Gao and Darryl Nousome and David V Conti and Ye Feng and Matthew A Allison and Zorayr Arzumanyan and Thomas A Buchanan and Yii-Der Ida Chen and Pauline M Genter and Mark O Goodarzi and Yang Hai and Willa Hsueh and Eli Ipp and Fouad R Kandeel and Kelvin Lam and Xiaohui Li and Jerry L Nadler and Leslie J Raffel and Kathryn Roll and Kevin Sandow and Jingyi Tan and Kent D Taylor and Anny H Xiang and Jie Yao and Astride Audirac-Chalifour and Jose de Jesus Peralta Romero and Fernando Hartwig and Bernando Horta and John Blangero and Joanne E Curran and Ravindranath Duggirala and Donna E Lehman and Sobha Puppala and Laura Fejerman and Esther M John and Carlos Aguilar-Salinas and Noël P Burtt and Jose C Florez and Humberto García-Ortíz and Clicerio González-Villalpando and Josep Mercader and Lorena Orozco and Teresa Tusié-Luna and Estela Blanco and Sheila Gahagan and Nancy J Cox and Craig Hanis and Nancy F Butte and Shelley A Cole and Anthony G Comuzzie and V Saroja Voruganti and Rebecca Rohde and Yujie Wang and Tamar Sofer and Elad Ziv and Struan F A Grant and Andres Ruiz-Linares and Jerome I Rotter and Christopher A Haiman and Esteban J Parra and Miguel Cruz and Ruth J F Loos and Kari E North},
doi = {10.1016/j.xhgg.2022.100149},
issn = {2666-2477},
year = {2023},
date = {2023-01-01},
journal = {HGG Adv},
volume = {4},
number = {1},
pages = {100149},
abstract = {[This corrects the article DOI: 10.1016/j.xhgg.2022.100099.].},
keywords = {},
pubstate = {published},
tppubtype = {misc}
}
[This corrects the article DOI: 10.1016/j.xhgg.2022.100099.].
Zhou, Hang | Kember, Rachel L | Deak, Joseph D | Xu, Heng | Toikumo, Sylvanus | Yuan, Kai | Lind, Penelope A | Farajzadeh, Leila | Wang, Lu | Hatoum, Alexander S | Johnson, Jessica | Lee, Hyunjoon | Mallard, Travis T | Xu, Jiayi | Johnston, Keira J A | Johnson, Emma C | Galimberti, Marco | Dao, Cecilia | Levey, Daniel F | Overstreet, Cassie | Byrne, Enda M | Gillespie, Nathan A | Gordon, Scott | Hickie, Ian B | Whitfield, John B | Xu, Ke | Zhao, Hongyu | Huckins, Laura M | Davis, Lea K | Sanchez-Roige, Sandra | Madden, Pamela A F | Heath, Andrew C | Medland, Sarah E | Martin, Nicholas G | Ge, Tian | Smoller, Jordan W | Hougaard, David M | Børglum, Anders D | Demontis, Ditte | Krystal, John H | Gaziano, J Michael | Edenberg, Howard J | Agrawal, Arpana | | Justice, Amy C | Stein, Murray B | Kranzler, Henry R | Gelernter, Joel
Multi-ancestry study of the genetics of problematic alcohol use in >1 million individuals Miscellaneous
2023.
Abstract | Links | BibTeX | Tags:
@misc{pmid36747741,
title = {Multi-ancestry study of the genetics of problematic alcohol use in >1 million individuals},
author = {Hang Zhou and Rachel L Kember and Joseph D Deak and Heng Xu and Sylvanus Toikumo and Kai Yuan and Penelope A Lind and Leila Farajzadeh and Lu Wang and Alexander S Hatoum and Jessica Johnson and Hyunjoon Lee and Travis T Mallard and Jiayi Xu and Keira J A Johnston and Emma C Johnson and Marco Galimberti and Cecilia Dao and Daniel F Levey and Cassie Overstreet and Enda M Byrne and Nathan A Gillespie and Scott Gordon and Ian B Hickie and John B Whitfield and Ke Xu and Hongyu Zhao and Laura M Huckins and Lea K Davis and Sandra Sanchez-Roige and Pamela A F Madden and Andrew C Heath and Sarah E Medland and Nicholas G Martin and Tian Ge and Jordan W Smoller and David M Hougaard and Anders D Børglum and Ditte Demontis and John H Krystal and J Michael Gaziano and Howard J Edenberg and Arpana Agrawal and and Amy C Justice and Murray B Stein and Henry R Kranzler and Joel Gelernter},
doi = {10.1101/2023.01.24.23284960},
year = {2023},
date = {2023-01-01},
journal = {medRxiv},
abstract = {Problematic alcohol use (PAU) is a leading cause of death and disability worldwide. To improve our understanding of the genetics of PAU, we conducted a large cross-ancestry meta-analysis of PAU in 1,079,947 individuals. We observed a high degree of cross-ancestral similarity in the genetic architecture of PAU and identified 110 independent risk variants in within- and cross-ancestry analyses. Cross-ancestry fine-mapping improved the identification of likely causal variants. Prioritizing genes through gene expression and/or chromatin interaction in brain tissues identified multiple genes associated with PAU. We identified existing medications for potential pharmacological studies by drug repurposing analysis. Cross-ancestry polygenic risk scores (PRS) showed better performance in independent sample than single-ancestry PRS. Genetic correlations between PAU and other traits were observed in multiple ancestries, with other substance use traits having the highest correlations. The analysis of diverse ancestries contributed significantly to the findings, and fills an important gap in the literature.},
keywords = {},
pubstate = {published},
tppubtype = {misc}
}
Problematic alcohol use (PAU) is a leading cause of death and disability worldwide. To improve our understanding of the genetics of PAU, we conducted a large cross-ancestry meta-analysis of PAU in 1,079,947 individuals. We observed a high degree of cross-ancestral similarity in the genetic architecture of PAU and identified 110 independent risk variants in within- and cross-ancestry analyses. Cross-ancestry fine-mapping improved the identification of likely causal variants. Prioritizing genes through gene expression and/or chromatin interaction in brain tissues identified multiple genes associated with PAU. We identified existing medications for potential pharmacological studies by drug repurposing analysis. Cross-ancestry polygenic risk scores (PRS) showed better performance in independent sample than single-ancestry PRS. Genetic correlations between PAU and other traits were observed in multiple ancestries, with other substance use traits having the highest correlations. The analysis of diverse ancestries contributed significantly to the findings, and fills an important gap in the literature.
2022
Brault, Julie | Liu, Taylor | Liu, Siyuan | Lawson, Amanda | Choi, Uimook | Kozhushko, Nikita | Bzhilyanskaya, Vera | Pavel-Dinu, Mara | Meis, Ronald J | Eckhaus, Michael A | Burkett, Sandra S | Bosticardo, Marita | Kleinstiver, Benjamin P | Notarangelo, Luigi D | Lazzarotto, Cicera R | Tsai, Shengdar Q | Wu, Xiaolin | Dahl, Gary A | Porteus, Matthew H | Malech, Harry L | Ravin, Suk See De
CRISPR-Cas9-AAV versus lentivector transduction for genome modification of X-linked severe combined immunodeficiency hematopoietic stem cells Journal Article
In: Front Immunol, vol. 13, pp. 1067417, 2022, ISSN: 1664-3224.
Abstract | Links | BibTeX | Tags:
@article{pmid36685559,
title = {CRISPR-Cas9-AAV versus lentivector transduction for genome modification of X-linked severe combined immunodeficiency hematopoietic stem cells},
author = {Julie Brault and Taylor Liu and Siyuan Liu and Amanda Lawson and Uimook Choi and Nikita Kozhushko and Vera Bzhilyanskaya and Mara Pavel-Dinu and Ronald J Meis and Michael A Eckhaus and Sandra S Burkett and Marita Bosticardo and Benjamin P Kleinstiver and Luigi D Notarangelo and Cicera R Lazzarotto and Shengdar Q Tsai and Xiaolin Wu and Gary A Dahl and Matthew H Porteus and Harry L Malech and Suk See De Ravin},
doi = {10.3389/fimmu.2022.1067417},
issn = {1664-3224},
year = {2022},
date = {2022-01-01},
journal = {Front Immunol},
volume = {13},
pages = {1067417},
abstract = {INTRODUCTION: gene therapy for treatment of Inborn errors of Immunity (IEIs) have demonstrated significant clinical benefit in multiple Phase I/II clinical trials. Current approaches rely on engineered retroviral vectors to randomly integrate copy(s) of gene-of-interest in autologous hematopoietic stem/progenitor cells (HSPCs) genome permanently to provide gene function in transduced HSPCs and their progenies. To circumvent concerns related to potential genotoxicities due to the random vector integrations in HSPCs, targeted correction with CRISPR-Cas9-based genome editing offers improved precision for functional correction of multiple IEIs.nnMETHODS: We compare the two approaches for integration of transgene for functional correction of HSPCs from patients with X-linked Severe Combined Immunodeficiency (SCID-X1 or XSCID); delivery current clinical lentivector (LV)- versus targeted insertion (TI) of homology-directed repair (HDR) when using an adeno-associated virus (AAV)- donor following double-strand DNA break at the endogenous locus.nnRESULTS AND DISCUSSION: differentiation of LV- or TI-treated XSCID HSPCs similarly overcome differentiation block into Pre-T-I and Pre-T-II lymphocytes but we observed significantly superior development of NK cells when corrected by TI (40.7% versus 4.1%, p = 0.0099). Transplants into immunodeficient mice demonstrated robust engraftment (8.1% and 23.3% in bone marrow) for LV- and TI- HSPCs with efficient T cell development following TI- in all four patients' HSPCs. Extensive specificity analysis of CRISPR-Cas9 editing with rhAmpSeq covering 82 predicted off-target sites found no evidence of indels in edited cells before () or following transplant, in stark contrast to LV's non-targeted vector integration sites. Together, the improved efficiency and safety of correction CRISPR-Cas9-based TI approach provides a strong rationale for a clinical trial for treatment of XSCID patients.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
INTRODUCTION: gene therapy for treatment of Inborn errors of Immunity (IEIs) have demonstrated significant clinical benefit in multiple Phase I/II clinical trials. Current approaches rely on engineered retroviral vectors to randomly integrate copy(s) of gene-of-interest in autologous hematopoietic stem/progenitor cells (HSPCs) genome permanently to provide gene function in transduced HSPCs and their progenies. To circumvent concerns related to potential genotoxicities due to the random vector integrations in HSPCs, targeted correction with CRISPR-Cas9-based genome editing offers improved precision for functional correction of multiple IEIs.nnMETHODS: We compare the two approaches for integration of transgene for functional correction of HSPCs from patients with X-linked Severe Combined Immunodeficiency (SCID-X1 or XSCID); delivery current clinical lentivector (LV)- versus targeted insertion (TI) of homology-directed repair (HDR) when using an adeno-associated virus (AAV)- donor following double-strand DNA break at the endogenous locus.nnRESULTS AND DISCUSSION: differentiation of LV- or TI-treated XSCID HSPCs similarly overcome differentiation block into Pre-T-I and Pre-T-II lymphocytes but we observed significantly superior development of NK cells when corrected by TI (40.7% versus 4.1%, p = 0.0099). Transplants into immunodeficient mice demonstrated robust engraftment (8.1% and 23.3% in bone marrow) for LV- and TI- HSPCs with efficient T cell development following TI- in all four patients' HSPCs. Extensive specificity analysis of CRISPR-Cas9 editing with rhAmpSeq covering 82 predicted off-target sites found no evidence of indels in edited cells before () or following transplant, in stark contrast to LV's non-targeted vector integration sites. Together, the improved efficiency and safety of correction CRISPR-Cas9-based TI approach provides a strong rationale for a clinical trial for treatment of XSCID patients.
Cole, Joanne B | Westerman, Kenneth E | Manning, Alisa K | Florez, Jose C | Hirschhorn, Joel N
Genetic heritability as a tool to evaluate the precision of 24-hour recall dietary questionnaire variables in UK Biobank Journal Article
In: Front Genet, vol. 13, pp. 1070511, 2022, ISSN: 1664-8021.
Abstract | Links | BibTeX | Tags:
@article{pmid36685884,
title = {Genetic heritability as a tool to evaluate the precision of 24-hour recall dietary questionnaire variables in UK Biobank},
author = {Joanne B Cole and Kenneth E Westerman and Alisa K Manning and Jose C Florez and Joel N Hirschhorn},
doi = {10.3389/fgene.2022.1070511},
issn = {1664-8021},
year = {2022},
date = {2022-01-01},
journal = {Front Genet},
volume = {13},
pages = {1070511},
abstract = {A variety of statistical approaches in nutritional epidemiology have been developed to enhance the precision of dietary variables derived from longitudinal questionnaires. Correlation with biomarkers is often used to assess the relative validity of these different approaches, however, validated biomarkers do not always exist and are costly and laborious to collect. We present a novel high-throughput approach which utilizes the modest but importantly non-zero influence of genetic variation on variation in dietary intake to compare different statistical transformations of dietary variables. Specifically, we compare the heritability of crude averages with Empirical Bayes weighted averages for 302 correlated dietary variables from multiple 24-hour recall questionnaires in 177 K individuals in UK Biobank. Overall, the crude averages for frequency of consumption are more heritable than their Empirical Bayes counterparts only when the reliability of that item across questionnaires is high (measured by intra-class correlation), otherwise, the Empirical Bayes approach (for both unreliably measured frequencies and for average quantities independent of reliability) leads to higher heritability estimates. We also find that the more heritable versions of each dietary variable lead to stronger underlying statistical associations with specific genetic loci, many of which have well-known mechanisms, further supporting heritability as an alternative metric for relative validity in nutritional epidemiology and beyond.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
A variety of statistical approaches in nutritional epidemiology have been developed to enhance the precision of dietary variables derived from longitudinal questionnaires. Correlation with biomarkers is often used to assess the relative validity of these different approaches, however, validated biomarkers do not always exist and are costly and laborious to collect. We present a novel high-throughput approach which utilizes the modest but importantly non-zero influence of genetic variation on variation in dietary intake to compare different statistical transformations of dietary variables. Specifically, we compare the heritability of crude averages with Empirical Bayes weighted averages for 302 correlated dietary variables from multiple 24-hour recall questionnaires in 177 K individuals in UK Biobank. Overall, the crude averages for frequency of consumption are more heritable than their Empirical Bayes counterparts only when the reliability of that item across questionnaires is high (measured by intra-class correlation), otherwise, the Empirical Bayes approach (for both unreliably measured frequencies and for average quantities independent of reliability) leads to higher heritability estimates. We also find that the more heritable versions of each dietary variable lead to stronger underlying statistical associations with specific genetic loci, many of which have well-known mechanisms, further supporting heritability as an alternative metric for relative validity in nutritional epidemiology and beyond.
The Center for Genomic Medicine (CGM) comprises one of the largest and most vibrant hubs of genomic medicine research in the world. The CGM includes 46 faculty collaborating to define the ‘genomic medicine cycle’ – which envisages a genomics community seeking to advance research from basic genomics research to ultimately using genome information for diagnostics and targeted therapeutics. All of our investigators are faculty at Harvard Medical School, and many members of our community are also investigators at the Broad Institute of Harvard and MIT.
