Genetic variants near MLST8 and DHX57 affect the epigenetic age of the cerebellum

Ake T. Lu, Eilis Hannon, Morgan E. Levine, Ke Hao, Eileen M. Crimmins, Katie Lunnon, Alexey Kozlenkov, Jonathan Mill, Stella Dracheva, Steve Horvath

Research output: Contribution to journalArticlepeer-review

58 Scopus citations

Abstract

DNA methylation (DNAm) levels lend themselves for defining an epigenetic biomarker of aging known as the 'epigenetic clock'. Our genome-wide association study (GWAS) of cerebellar epigenetic age acceleration identifies five significant (P<5.0 × 10-8) SNPs in two loci: 2p22.1 (inside gene DHX57) and 16p13.3 near gene MLST8 (a subunit of mTOR complex 1 and 2). We find that the SNP in 16p13.3 has a cis-acting effect on the expression levels of MLST8 (P=6.9 × 10-18) in most brain regions. In cerebellar samples, the SNP in 2p22.1 has a cis-effect on DHX57 (P=4.4 × 10-5). Gene sets found by our GWAS analysis of cerebellar age acceleration exhibit significant overlap with those of Alzheimer's disease (P=4.4 × 10-15), age-related macular degeneration (P=6.4 × 10-6), and Parkinson's disease (P=2.6 × 10-4). Overall, our results demonstrate the utility of a new paradigm for understanding aging and age-related diseases: it will be fruitful to use epigenetic tissue age as endophenotype in GWAS.

Original languageEnglish
Article number10561
JournalNature Communications
Volume7
DOIs
StatePublished - 2 Feb 2016

Fingerprint

Dive into the research topics of 'Genetic variants near MLST8 and DHX57 affect the epigenetic age of the cerebellum'. Together they form a unique fingerprint.

Cite this