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

Ake T. Lu, Eilis Hannon, Morgan E. Levine, Eileen M. Crimmins, Katie Lunnon, Jonathan Mill, Daniel H. Geschwind and Steve Horvath ()
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Ake T. Lu: David Geffen School of Medicine, University of California Los Angeles
Eilis Hannon: University of Exeter Medical School, University of Exeter, RILD Building, Barrack Road
Morgan E. Levine: David Geffen School of Medicine, University of California Los Angeles
Eileen M. Crimmins: Davis School of Gerontology, University of Southern California, Ethel Percy Andrus Gerontology Center
Katie Lunnon: University of Exeter Medical School, University of Exeter, RILD Building, Barrack Road
Jonathan Mill: University of Exeter Medical School, University of Exeter, RILD Building, Barrack Road
Daniel H. Geschwind: David Geffen School of Medicine, University of California Los Angeles
Steve Horvath: David Geffen School of Medicine, University of California Los Angeles

Nature Communications, 2017, vol. 8, issue 1, 1-14

Abstract: Abstract 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

Date: 2017
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DOI: 10.1038/ncomms15353

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