Genome-wide association analyses identify 143 risk variants and putative regulatory mechanisms for type 2 diabetes.
Nat Commun
; 9(1): 2941, 2018 07 27.
Article
en En
| MEDLINE
| ID: mdl-30054458
ABSTRACT
Type 2 diabetes (T2D) is a very common disease in humans. Here we conduct a meta-analysis of genome-wide association studies (GWAS) with ~16 million genetic variants in 62,892 T2D cases and 596,424 controls of European ancestry. We identify 139 common and 4 rare variants associated with T2D, 42 of which (39 common and 3 rare variants) are independent of the known variants. Integration of the gene expression data from blood (n = 14,115 and 2765) with the GWAS results identifies 33 putative functional genes for T2D, 3 of which were targeted by approved drugs. A further integration of DNA methylation (n = 1980) and epigenomic annotation data highlight 3 genes (CAMK1D, TP53INP1, and ATP5G1) with plausible regulatory mechanisms, whereby a genetic variant exerts an effect on T2D through epigenetic regulation of gene expression. Our study uncovers additional loci, proposes putative genetic regulatory mechanisms for T2D, and provides evidence of purifying selection for T2D-associated variants.
Texto completo:
1
Base de datos:
MEDLINE
Asunto principal:
Variación Genética
/
Regulación de la Expresión Génica
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Predisposición Genética a la Enfermedad
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Diabetes Mellitus Tipo 2
/
Estudio de Asociación del Genoma Completo
Tipo de estudio:
Etiology_studies
/
Risk_factors_studies
/
Systematic_reviews
Idioma:
En
Revista:
Nat Commun
Asunto de la revista:
BIOLOGIA
/
CIENCIA
Año:
2018
Tipo del documento:
Article