期刊
NATURE COMMUNICATIONS
卷 8, 期 -, 页码 -出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/ncomms15353
关键词
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资金
- Paul G. Allen Family Foundation
- National Institutes of Health [NIA/NIH 5R01AG042511-02, NIAGADS P30AG10161, R01AG15819, AG/NIA NIH R01AG17917, AG/NIA NIH HHS R01AG36042]
Identifying genes regulating the pace of epigenetic ageing represents a new frontier in genome-wide association studies (GWASs). Here using 1,796 brain samples from 1,163 individuals, we carry out a GWAS of two DNA methylation-based biomarkers of brain age: the epigenetic ageing rate and estimated proportion of neurons. Locus 17q11.2 is significantly associated (P = 4.5 x 10(-9)) with the ageing rate across five brain regions and harbours a cis-expression quantitative trait locus for EFCAB5 (P = 3.4 x 10(-20)). Locus 1p36.12 is significantly associated (P = 2.2 x 10(-8)) with epigenetic ageing of the prefrontal cortex, independent of the proportion of neurons. Our GWAS of the proportion of neurons identified two genome-wide significant loci (10q26 and 12p13.31) and resulted in a gene set that overlaps significantly with sets found by GWAS of age-related macular degeneration (P = 1.4 x 10(-12)), ulcerative colitis (P < 1.0 x 10(-20)), type 2 diabetes (P = 2.8 x 10(-13)), hip/waist circumference in men (P = 1.1 x 10(-9)), schizophrenia (P = 1.6 x 10(-9)), cognitive decline (P = 5.3 x 10(-4)) and Parkinson's disease (P = 8.6 x 10(-3)).
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