• We assembled an ancestrally diverse collection of genome-wide association studies (GWAS) of type 2 diabetes (T2D) in 180,834 affected individuals and 1,159,055 controls (48.9% non-European descent) through the Diabetes Meta-Analysis of Trans-Ethnic association studies (DIAMANTE) Consortium. Multi-ancestry GWAS meta-analysis identified 237 loci attaining stringent genome-wide significance (P < 5 x 10(-9)), which were delineated to 338 distinct association signals. Fine-mapping of these signals was enhanced by the increased sample size and expanded population diversity of the multi-ancestry meta-analysis, which localized 54.4% of T2D associations to a single variant with >50% posterior probability. This improved fine-mapping enabled systematic assessment of candidate causal genes and molecular mechanisms through which T2D associations are mediated, laying the foundations for functional investigations. Multi-ancestry genetic risk scores enhanced transferability of T2D prediction across diverse populations. Our study provides a step toward more effective clinical translation of T2D GWAS to improve global health for all, irrespective of genetic background. Genome-wide association and fine-mapping analyses in ancestrally diverse populations implicate candidate causal genes and mechanisms underlying type 2 diabetes. Trans-ancestry genetic risk scores enhance transferability across populations.

Ämnesord

MEDICIN OCH HÄLSOVETENSKAP  -- Medicinska och farmaceutiska grundvetenskaper -- Medicinsk genetik (hsv//swe)

MEDICAL AND HEALTH SCIENCES  -- Basic Medicine -- Medical Genetics (hsv//eng)

Nyckelord

ancestry group

Article

comparative study

controlled study

disease risk assessment

gene mapping

genetic association

genetic background

genetic heterogeneity

genetic risk score

genome-wide association study

human

major clinical study

missense mutation

multiomics

non insulin dependent diabetes mellitus

population genetics

quantitative trait locus

single nucleotide polymorphism

ethnicity

genetic predisposition

genetics

meta analysis

risk factor

Diabetes Mellitus, Type 2

Ethnicity

Genetic Predisposition to Disease

Genome-Wide Association Study

Humans

Polymorphism, Single Nucleotide

Risk Factors

Publikations- och innehållstyp

ref (ämneskategori)

art (ämneskategori)