Variants to Diagnosis & Treatment

Variants to Diagnosis & Treatment2023-07-19T16:02:38-04:00

Use of understanding gained in the genomic medicine cycle to refine treatment, diagnosis, or promote new therapeutics for rare or common human disease.

News | Variants to Diagnosis & Treatment

Identification of Genetic Variation Influencing Metformin Response in a Multi-Ancestry Genome-Wide Association Study in the Diabetes Prevention Program (DPP)

Genome-wide significant loci for metformin response in type 2 diabetes reported elsewhere have not replicated in the Diabetes Prevention Program (DPP). To assess pharmacogenetic interactions in pre-diabetes, CGM investigator Jose Florez and colleagues conducted a GWAS in the DPP. Cox proportional hazards models tested associations with diabetes incidence in the metformin (n=876) and placebo (n=887) arms. Multiple linear regression assessed association with one-year change in metformin-related quantitative traits, adjusted for baseline trait, age, sex, and 10 ancestry principal components. The investigators identified four genome-wide significant variants after correcting for correlated traits (p<9×10-9). These novel ethnic-specific associations require further investigation but may have implications for tailored therapy.

Read more in Diabetes

December 12, 2022

Publication

CGM Primary Investigator

Jose Florez
December 12, 2022|

Sensitive periods in development and risk for psychiatric disorders and related endpoints: A systematic review of child maltreatment findings

Childhood maltreatment increases the likelihood of mental health problems, but outcomes vary widely. The timing of maltreatment may help explain these outcome differences. Specifically, impacts might be stronger during sensitive periods in development when the brain is maximally sensitive to particular types of environmental input. Is there consensus about peak periods of sensitivity to childhood maltreatment? This review led by CGM investigator Erin Dunn, analysis of observational studies in humans found that most studies (75%, or 89 of 118 studies) reported timing effects, but did not identify consistent sensitive periods across studies. The investigators also examined study characteristics to inform a discussion of practices to support future research.

Read more in The Lancet Psychiatry

December 11, 2022

Publication Name

CGM Primary Investigator

December 11, 2022|

‘Holy moly, that is a slow burn’: Research center in Boston aims to jump-start precision psychiatry

CGM PI and Director of the PNGU, Jordan Smoller, was featured in GBH to discuss the inception and research bing conducted in the Center for Precision Psychiatry.

Learn more at WGBH.

December 10, 2022

Source

CGM Primary Investigator

Jordan Smoller
December 10, 2022|

Down Syndrome Program: new research paper on COVID-19 in group homes

For the past 2 years, during the pandemic, CGM PI, Brian Skotko, and his multidisciplinary team set up and implemented a randomized control trial to see if they could design a multimodal behavioral intervention that could reduce COVID-19 infection, hospitalization, and death for those persons living in group homes in MA. They focused on people with serious mental illness (SMI) and people with intellectual and/or developmental disabilities (ID/DD)—and the staff who work with them in group homes. This “protocol paper” describes our unique design: a hybrid type 1 effective-implementation cluster randomized trial, which means that half of the 400 participating group homes got our tailored intervention (and the other half continued to receive the statewide recommendations). For the past 2 years, they have been implementing this trial, which has now come to a close.

December 9, 2022

Publication

CGM Primary Investigator

Brian Skotko
December 9, 2022|

Polygenic risk scores for diverse cohorts

Even though the application of polygenic risk scores (PRSs) in precision medicine has been widely explored, there is limited evidence of its clinical utility across disease areas. To facilitate the development of best practices for PRS calculation, Alicia Martin, and colleagues used data from Global Biobank Meta-analysis Initiative. The researchers explored methods for PRS calculation and prediction accuracy in nine different biobanks for 14 disease endpoints. They outline a framework for PRS analyses of multi-ancestry genome-wide association studies across multiple biobanks and highlight the importance of best practices for PRS in the biobank-scale genomics era.

Read more in Cell Genomics

December 8, 2022

Publication

CGM Primary Investigator

December 8, 2022|

Faculty | Variants to Diagnosis & Treatment

Phil H. Lee, PhD

Categories: Variants to Diagnosis, Variants to Disease & Traits, Variants to Function & Mechanism
Harvard Medical School: Assistant Professor of Psychiatry
Massachusetts General Hospital: Assistant in Research
Assistant in Research, Massachusetts General Hospital
Assistant Professor, Harvard Medical School

We use computational and statistical approaches to understand the genetic bases of complex neuropsychiatric traits and mental disorders. Multivariate pathway analysis forms the backbone of our research on identifying disease risk genes and mechanisms. We also apply multi-modal data analysis integrating genomic and neuroimaging data.

Phil H. Lee, PhD

Assistant Professor of Psychiatry, Harvard Medical School

Marcy E. MacDonald, PhD

Categories: Populations to Variants, Variants to Diagnosis, Variants to Disease & Traits, Variants to Function & Mechanism
Harvard Medical School: Professor of Neurology
Massachusetts General Hospital: Research (Non-Clinical) Staff
Research (Non-Clinical) Staff, Massachusetts General Hospital
Professor of Neurology, Harvard Medical School

Our research, evolving from the discovery of the genetic causes of inherited brain disorders (hereditary spastic paraparesis, neurofibromatosis, neuronal ceroid lipofuscinosis, Huntington’s disease), is now largely focused on the DNA variants that modify the effects of the unstable expanded CAG repeat that causes Huntington’s disease. We do molecular genetic studies with disease and population cohorts and genetically precise model systems. Our goal is to enable timely intervention, diagnosis and disease-management.

Marcy E. MacDonald, PhD

Professor of Neurology, Harvard Medical School

Alicia Martin, PhD

Categories: Populations to Variants, Training Program Faculty, Variants to Diagnosis, Variants to Disease & Traits
Harvard Medical School: Assistant Professor of Medicine
Massachusetts General Hospital: Assistant Investigator
Assistant Investigator, Massachusetts General Hospital
Assistant Professor, Harvard Medical School

As a population and statistical genetics lab, our research examines the role of human history in shaping global genetic and phenotypic diversity. Given vast Eurocentric study biases, we investigate the generalizability of knowledge gained from large-scale genetic studies across globally diverse populations. We are focused on ensuring that the translation of genetic technologies particularly via polygenic risk does not exacerbate health disparities induced by these study biases. Towards this end, we are developing statistical methods, community resources for genomics, and research capacity for multi-ancestry studies especially in underrepresented populations.

Alicia Martin, PhD

Assistant Professor, Harvard Medical School

Heidi L. Rehm, PhD

Categories: Populations to Variants, Training Program Faculty, Variants to Diagnosis, Variants to Disease & Traits
Harvard Medical School: Professor of Pathology
Massachusetts General Hospital: Chief Genomics Officer
Chief Genomics Officer, Massachusetts General Hospital
Professor of Pathology, Harvard Medical School

The Translational Genomics Group (TGG) has a mission to support the discovery of the genetic basis of rare disease and translate our work into medical practice by focusing on community-centered projects that promote collaboration, data sharing and open science. Heidi Rehm leads the TGG, with co-leadership by Anne O’Donnell-Luria for the rare disease group and Mark Daly for the gnomAD project. TGG is composed of a multidisciplinary team of researchers, clinicians, computational biologists, and software engineers. We are located at Massachusetts General Hospital and the Broad Institute of MIT and Harvard.

Heidi L. Rehm, PhD

Professor of Pathology, Harvard Medical School

Jeremiah M. Scharf, MD, PhD

Categories: Populations to Variants, Training Program Faculty, Variants to Diagnosis, Variants to Disease & Traits, Variants to Function & Mechanism
Harvard Medical School: Assistant Professor of Neurology
Massachusetts General Hospital: Physician-Scientist
Physician-Scientist, Massachusetts General Hospital
Assistant Professor of Neurology, Harvard Medical School

The Scharf lab investigates the genetic and neurobiological mechanisms of Tourette Syndrome (TS) and related developmental neuropsychiatric disorders that lie at the interface between traditional concepts of neurologic and psychiatric disease, including obsessive compulsive spectrum disorders (OCD/OCSD) and attention-deficit hyperactivity disorder (ADHD). We conduct genetic and clinical research to identify both genetic and non-genetic risk factors that contribute to the predisposition of TS, ADHD, and OCD in patients and families. We hope to identify novel targets for treatment, to understand the course of TS and related conditions at a patient-specific level, and to better predict treatment response.

Jeremiah M. Scharf, MD, PhD

Assistant Professor of Neurology, Harvard Medical School

Jordan W. Smoller, MD, ScD

Categories: Training Program Faculty, Variants to Diagnosis, Variants to Disease & Traits, Variants to Function & Mechanism
Harvard Medical School: Professor of Psychiatry
Massachusetts General Hospital: MGH Trustees Endowed Chair in Psychiatric Neuroscience
Massachusetts General Hospital: MGH Trustees Endowed Chair in Psychiatric Neuroscience
MGH Trustees Endowed Chair in Psychiatric Neuroscience, Massachusetts General Hospital
MGH Trustees Endowed Chair in Psychiatric Neuroscience, Massachusetts General Hospital
Professor of Psychiatry, Harvard Medical School

The focus of Dr. Smoller’s research interests has been:

  • Understanding the genetic and environmental determinants of psychiatric disorders across the lifespan.
  • Integrating genomics and neuroscience to unravel how genes affect brain structure and function.
  • Using “big data”, including electronic health records and genomics, to advance precision medicine.

Jordan W. Smoller, MD, ScD

Professor of Psychiatry, Harvard Medical School

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