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Nat Commun. 2017 May 18;8:15353. doi: 10.1038/ncomms15353.

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

Author information

1
Department of Human Genetics, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, California 90095, USA.
2
University of Exeter Medical School, University of Exeter, RILD Building, Barrack Road, Exeter EX2 5DW, UK.
3
Center for Neurobehavioral Genetics, University of California Los Angeles, Los Angeles, California 90095, USA.
4
Davis School of Gerontology, University of Southern California, Ethel Percy Andrus Gerontology Center, 3715 McClintock Avenue, Los Angeles, California 90089-0191, USA.
5
Institute of Psychiatry, King's College London, London SE5 8AF, UK.
6
Neurogenetics Program, Department of Neurology, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, California 90095, USA.
7
Center for Autism Research and Treatment, Semel Institute, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, California 90095, USA.
8
Department of Biostatistics, School of Public Health, University of California Los Angeles, Los Angeles, California 90095, USA.

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<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).

PMID:
28516910
PMCID:
PMC5454371
DOI:
10.1038/ncomms15353
[Indexed for MEDLINE]
Free PMC Article

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