PT  - JOURNAL ARTICLE
AU  - Angli Xue
AU  - Yang Wu
AU  - Zhihong Zhu
AU  - Futao Zhang
AU  - Kathryn E Kemper
AU  - Zhili Zheng
AU  - Loic Yengo
AU  - Luke R. Lloyd-Jones
AU  - Julia Sidorenko
AU  - Yeda Wu
AU  - eQTLGen Consortium
AU  - Allan F McRae
AU  - Peter M Visscher
AU  - Jian Zeng
AU  - Jian Yang
TI  - Novel susceptibility loci and genetic regulation mechanisms for type 2 diabetes
AID  - 10.1101/284570
DP  - 2018 Jan 01
TA  - bioRxiv
PG  - 284570
4099  - http://biorxiv.org/content/early/2018/03/20/284570.short
4100  - http://biorxiv.org/content/early/2018/03/20/284570.full
AB  - We conducted a meta-analysis of genome-wide association studies (GWAS) with ∼16 million genotyped/imputed genetic variants in 62,892 type 2 diabetes (T2D) cases and 596,424 controls of European ancestry. We identified 139 common and 4 rare (minor allele frequency < 0.01) variants associated with T2D, 42 of which (39 common and 3 rare variants) were independent of the known variants. Integration of the gene expression data from blood (n = 14,115 and 2,765) and other T2D-relevant tissues (n = up to 385) with the GWAS results identified 33 putative functional genes for T2D, three of which were targeted by approved drugs. A further integration of DNA methylation (n = 1,980) and epigenomic annotations data highlighted three putative T2D genes (CAMK1D, TP53INP1 and ATP5G1) with plausible regulatory mechanisms whereby a genetic variant exerts an effect on T2D through epigenetic regulation of gene expression. We further found evidence that the T2D-associated loci have been under purifying selection.