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J Hum Genet ; 63(11): 1109-1117, 2018 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-30135545

RESUMEN

African American women are disproportionately affected by type 2 diabetes. Genetic factors may explain part of the excess risk. More than 100 genetic variants have been associated with risk of type 2 diabetes, but most studies have been conducted in white populations. Two genome-wide association studies (GWAS) in African Americans have identified three novel genetic variants only. We conducted admixture mapping using 2918 ancestral informative markers in 2632 cases of type 2 diabetes, and 2596 controls nested in the ongoing Black Women's Health Study cohort, with the goal of identifying genomic loci with local African ancestry associated with type 2 diabetes. In addition, we performed replication analysis of 71 previously identified index SNPs, and fine-mapped those genetic loci to identify better or new genetic variants associated with type 2 diabetes in African Americans. We found that individual African ancestry was associated with higher risk of type 2 diabetes. In addition, we identified two genomic regions, 3q26 and 12q23, with excess of African ancestry associated with higher risk of type 2 diabetes. Lastly, we replicated 8 out of 71 index SNPs from previous GWAS, including, for the first time in African Americans, the X-linked rs5945326 SNP near the DUSP9 gene. In addition, our fine-mapping efforts suggest independent signals at five loci. Our detailed analysis identified two genomic regions associated with risk of type 2 diabetes, and showed that many genetic risk variants are shared across ancestries.


Asunto(s)
Negro o Afroamericano/genética , Mapeo Cromosómico , Diabetes Mellitus Tipo 2/genética , Sitios Genéticos , Predisposición Genética a la Enfermedad , Polimorfismo de Nucleótido Simple , Adulto , Anciano , Cromosomas Humanos Par 12/genética , Cromosomas Humanos Par 3/genética , Fosfatasas de Especificidad Dual/genética , Femenino , Estudio de Asociación del Genoma Completo , Humanos , Persona de Mediana Edad , Fosfatasas de la Proteína Quinasa Activada por Mitógenos/genética
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