Blood DNA methylation sites predict death risk in a longitudinal study of 12, 300 individuals.

Aging
Elena ColicinoAndrea Baccarelli

Abstract

DNA methylation has fundamental roles in gene programming and aging that may help predict mortality. However, no large-scale study has investigated whether site-specific DNA methylation predicts all-cause mortality. We used the Illumina-HumanMethylation450-BeadChip to identify blood DNA methylation sites associated with all-cause mortality for 12, 300 participants in 12 Cohorts of the Heart and Aging Research in Genetic Epidemiology (CHARGE) Consortium. Over an average 10-year follow-up, there were 2,561 deaths across the cohorts. Nine sites mapping to three intergenic and six gene-specific regions were associated with mortality (P < 9.3x10-7) independently of age and other mortality predictors. Six sites (cg14866069, cg23666362, cg20045320, cg07839457, cg07677157, cg09615688)-mapping respectively to BMPR1B, MIR1973, IFITM3, NLRC5, and two intergenic regions-were associated with reduced mortality risk. The remaining three sites (cg17086398, cg12619262, cg18424841)-mapping respectively to SERINC2, CHST12, and an intergenic region-were associated with increased mortality risk. DNA methylation at each site predicted 5%-15% of all deaths. We also assessed the causal association of those sites to age-related chronic diseases by usin...Continue Reading

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Citations

Jul 9, 2021·Cancer Causes & Control : CCC·Laurie GrieshoberJennifer A Doherty
Aug 4, 2021·Environmental Health : a Global Access Science Source·Charles BenbrookRobin Mesnage

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Methods Mentioned

BETA
blood draw

Software Mentioned

IMPUTE
Bioconductor package lumi
CHARGE
KORA
ESTHER
PATHWAY
Functional Mapping and Annotation ( FUMA )
topGO
R
PhenoAge

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