Exome sequencing of 20,791 cases of type 2 diabetes and 24,440 controls.

ABSTRACT: Protein-coding genetic variants that strongly affect disease risk can yield relevant clues to disease pathogenesis. Here we report exome-sequencing analyses of 20,791 individuals with type 2 diabetes (T2D) and 24,440 non-diabetic control participants from 5 ancestries. We identify gene-level associations of rare variants (with minor allele frequencies of less than 0.5%) in 4 genes at exome-wide significance, including a series of more than 30 SLC30A8 alleles that conveys protection against T2D, and in 12 gene sets, including those corresponding to T2D drug targets (P = 6.1 × 10^-3) and candidate genes from knockout mice (P = 5.2 × 10^-3). Within our study, the strongest T2D gene-level signals for rare variants explain at most 25% of the heritability of the strongest com

SUBMITTER: Flannick J 

PROVIDER: S-EPMC6699738 | biostudies-literature | 2019 Jun

REPOSITORIES: biostudies-literature