Amit V. Khera - Center for Genomic Medicine

Dr. Khera is a physician-scientist with expertise in epidemiology, clinical medicine, and human genetics. Among his scientific contributions, he pioneered a new approach to quantify genetic risk for common diseases, developed biomarkers that provide new biologic insights, and analyzed large-scale gene sequencing data to highlight key pathways underlying risk for coronary artery disease. His research program uses genetic variation as a tool to uncover new biology and enable enhanced clinical care informed by inherited susceptibility.

Questions being addressed in the lab

What can the molecular signatures of inherited susceptibility teach us about disease biology?
What is the diagnostic yield and clinical utility of genetic testing across a range of important diseases?
How can genome interpretation enable tailored screening or preventive measures prior to disease onset?

Projects underway to answer these questions

Characterize genetic and non-genetic modifiers of the relationship between rare pathogenic mutations and phenotype.
Identify new pathways or biomarkers for a given disease, through molecular profiling of asymptomatic people at the extremes of a polygenic score distribution
Identify high-risk patients ‘flying under the radar’ within our MGH clinical practice and facilitate disclosure and tailored care within a preventive genomics clinical program

Answers Found

Rare genetic mutations in lipoprotein lipase prevent clearance of dietary fat from the circulation and are linked to increased risk for heart attack.
Familial hypercholesterolemia mutations are present in 2% of those with severely elevated cholesterol levels, but – if present – confer markedly increased risk of coronary artery disease.
A genome-wide polygenic score for coronary artery disease identifies 8% of the population with risk equivalent to a rare monogenic mutation.