Genetic architecture of epigenetic and neuronal ageing rates in human brain regions.

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Authors
Lu, A. T.
Hannon, E.
Levine, M. E.
Crimmins, E. M.
Lunnon, Katie
Mill, Jonathan
Geschwind, D. H.
Horvath, S.
Journal
Nature Communications
Type
Journal Article
Publisher
Nature
Rights
Archived with thanks to Nature communications
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 × 10(-9)) with the ageing rate across five brain regions and harbours a cis-expression quantitative trait locus for EFCAB5 (P=3.4 × 10(-20)). Locus 1p36.12 is significantly associated (P=2.2 × 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 × 10(-12)), ulcerative colitis (P<1.0 × 10(-20)), type 2 diabetes (P=2.8 × 10(-13)), hip/waist circumference in men (P=1.1 × 10(-9)), schizophrenia (P=1.6 × 10(-9)), cognitive decline (P=5.3 × 10(-4)) and Parkinson's disease (P=8.6 × 10(-3)).
Citation
Genetic architecture of epigenetic and neuronal ageing rates in human brain regions. 2017, 8:15353 Nat Commun
Note
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