James Meigs, MD

Institution: Massachusetts General Hospital
Research: Precursors to Type 2 Diabetes
Grants & Publications: Harvard Catalyst
Categories: MGH

Dr. Meigs has been a practicing primary care general internist at MGH for over 30 years, during which time his lab has focused on the cause and prevention of type 2 diabetes and cardiovascular disease using biochemical, genetic epidemiology and health services translational research approaches. He is a senior leader of many major large international T2D genomics consortia, including MAGIC, DIAGRAM, AAGILE, CHARGE- and TOPMed-diabetes, NIDDK T2D AMP/CMD and the VA’s MVP cardiometabolic work group. Dr. Meigs is also an experienced research mentor of over 50 early career investigators, including nine K-award recipients.

Current projects include:
TOPMed Omics of T2D, Quantitative Traits: We aim to use whole genome sequence and blood omic biomarkers in the NHLBI Trans-Omics for Precision Medicine (TOPMed) study to illuminate the pathobiology of type 2 diabetes (T2D) and its quantitative traits fasting glucose, insulin and hemoglobin A1c. We will integrate TOPMed results with beta cell-, liver-, fat- and muscle-specific omics and epigenomic annotation in the Accelerating Medicine Partnership (AMP) T2D Diabetes epiGenome Atlas and with hundreds of additional genomic trait associations in the AMP T2D Knowledge Portal for ‘in silico variant-to-function’ and phenomic studies aimed to find new approaches to address the global epidemic of T2D.

TOPMed Omics of CVD in T2D : We aim to use blood omic biomarkers in the NHLBI TOPMed study to illuminate the pathobiology of cardiovascular disease (CVD) in T2D. T2D is driving a major global epidemic of CVD, where CVD events occur over twice as frequently in people with T2D as without. The reasons for this excess risk are unknown but likely involve perturbations across multiple omic dimensions, including whole genome sequence variation and whole blood methylation, transcription, proteomics and metabolomics, where individually and together they contribute to novel pathways to CVD in T2D.

eMERGE Phase IV Clinical Center at Mass General Brigham: The discovery and clinical use of polygenic risk scores (PRS) for complex traits promises to dramatically change the practice of medicine. Our eMERGE IV grant will leverage a large Biobank and a rich electronic medical record to define the clinical impact of PRS derived from diverse populations and the clinical impact of returning these results along with family history and clinical risk information to participants and their healthcare providers.

Development of Polygenic Risk Scores for Diabetes and Complications across the Life Span in Populations of Diverse Ancestry: T1D and T2D, gestational diabetes (GDM) and related complications are excellent disease models to study the utility of polygenic risk scores (PRS) for predicting heterogenous and complex health outcomes in a setting where dramatic racial/ethnic and socioeconomic disparities exist. To address the disparities in PRS across ancestries, we have assembled a multi-disciplinary team to aggregate and analyze the largest existing genetic data from more than 1.8 M individuals (35% non-European) with T1D, T2D, GDM and glycemia-related complications and quantitative traits to improve the PRS prediction of diabetes and progression across the lifespan in diverse ancestries. Accomplishing the aims of this proposal will demonstrate how genomic data can inform more efficient and targeted preventive strategies within healthcare systems and across ethnically diverse populations