全基因组关联研究
生物
表观遗传学
遗传学
DNA甲基化
表观遗传学
遗传关联
表达数量性状基因座
基因
基因组
2型糖尿病
调节顺序
计算生物学
基因表达调控
单核苷酸多态性
基因表达
基因型
糖尿病
内分泌学
作者
Anke Xue,Yang Wu,Zhihong Zhu,Futao Zhang,Kathryn E. Kemper,Zhili Zheng,Loïc Yengo,Luke R. Lloyd‐Jones,Julia Sidorenko,Yeda Wu,Allan F. McRae,Peter M. Visscher,Jian Zeng,Jian Yang
标识
DOI:10.1038/s41467-018-04951-w
摘要
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.
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