Naslov
The trans-ancestral genomic architecture of glycemic traits

Autori
Chen, Ji ; Spracklen, Cassandra N. ; Marenne, Gaelle ; Varshney, Arushi et al.

Kolaboracija
Lifelines Cohort Study ; Metaanal Glucose Insulin Related

Izvornik
Nature Genetics (1061-4036) 53 (2021), 6; 840-860

Vrsta, podvrsta i kategorija rada
Radovi u časopisima, članak, znanstveni

Ključne riječi
WIDE ASSOCIATION ; INSULIN-RESISTANCE ; GENE-EXPRESSION ; DISEASE RISK ; VARIANTS ; GLUCOSE ; LOCI ; METAANALYSIS ; MECHANISMS ; HEMOGLOBIN

Sažetak
Glycemic traits are used to diagnose and monitor type 2 diabetes and cardiometabolic health. To date, most genetic studies of glycemic traits have focused on individuals of European ancestry. Here we aggregated genome-wide association studies comprising up to 281, 416 individuals without diabetes (30% non-European ancestry) for whom fasting glucose, 2-h glucose after an oral glucose challenge, glycated hemoglobin and fasting insulin data were available. Trans-ancestry and single- ancestry meta-analyses identified 242 loci (99 novel ; P < 5 x 10(-8)), 80% of which had no significant evidence of between-ancestry heterogeneity. Analyses restricted to individuals of European ancestry with equivalent sample size would have led to 24 fewer new loci. Compared with single-ancestry analyses, equivalent-sized trans- ancestry fine-mapping reduced the number of estimated variants in 99% credible sets by a median of 37.5%. Genomic-feature, gene-expression and gene-set analyses revealed distinct biological signatures for each trait, highlighting different underlying biological pathways. Our results increase our understanding of diabetes pathophysiology by using trans-ancestry studies for improved power and resolution. A trans- ancestry meta-analysis of GWAS of glycemic traits in up to 281, 416 individuals identifies 99 novel loci, of which one quarter was found due to the multi-ancestry approach, which also improves fine- mapping of credible variant sets.

Izvorni jezik
Engleski

Znanstvena područja
Temeljne medicinske znanosti

POVEZANOST RADA