Population-scale sequencing reveals rare-variant burden in early-onset cardiometabolic disease

Abstract

Rare coding variants contribute to cardiometabolic risk, but their aggregate burden is difficult to quantify. Whole-exome sequencing of 180,000 participants identified 14 genes with significant rare-variant associations, five of which are novel. Carriers of high-impact variants showed onset of disease on average nine years earlier than non-carriers.

Keywords

• genomics
• rare variants
• cardiometabolic disease