| Title: | Genome-wide association analyses identify 143 risk variants and putative regulatory mechanisms for type 2 diabetes |
| Journal: | Nature Communications |
| Published: | 27 Jul 2018 |
| Pubmed: | https://pubmed.ncbi.nlm.nih.gov/30054458/ |
| DOI: | https://doi.org/10.1038/s41467-018-04951-w |
| URL: | https://www.nature.com/articles/s41467-018-04951-w.pdf |
| Citations: | 643 (222 in last 2 years) as of 8 Aug 2024 |
Publication 8553
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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.</p>
15 Authors
- Angli Xue
- Yang Wu
- Zhihong Zhu
- Futao Zhang
- Kathryn E. Kemper
- Zhili Zheng
- Loic Yengo
- Luke R. Lloyd-Jones
- Julia Sidorenko
- Yeda Wu
- eQTLGen Consortium
- Allan F. McRae
- Peter M. Visscher
- Jian Zeng
- Jian Yang
1 Application
| Application ID | Title |
|---|---|
| 12505 | Dissecting the genetic basis of relationships between early-life and later-life events |
Enabling scientific discoveries that improve human health