Gene-level analysis of rare variants in 379,066 whole exome sequences identifies an association of GIGYF1 loss of function with type 2 diabetes.

ABSTRACT: Sequencing of large cohorts offers an unprecedented opportunity to identify rare genetic variants and to find novel contributors to human disease. We used gene-based collapsing tests to identify genes associated with glucose, HbA1c and type 2 diabetes (T2D) diagnosis in 379,066 exome-sequenced participants in the UK Biobank. We identified associations for variants in GCK, HNF1A and PDX1, which are known to be involved in Mendelian forms of diabetes. Notably, we uncovered novel associations for GIGYF1, a gene not previously implicated by human genetics in diabetes. GIGYF1 predicted loss of function (pLOF) variants associated with increased levels of glucose (0.77 mmol/L increase, p = 4.42 × 10^-12) and HbA1c (4.33 mmol/mol, p = 1.28 × 10^-14) as well as T2D diagnosis (OR

SUBMITTER: Deaton AM 

PROVIDER: S-EPMC8566487 | biostudies-literature | 2021 Nov

REPOSITORIES: biostudies-literature