Metabolomic markers reveal novel pathways of ageing and early development in human populations

作者：Cristina Menni, Gabriella Kastenmüller, Ann Kristin Petersen, Jordana T. Bell, Maria Psatha, Pei-Chien Tsai, Christian Gieger, Holger Schulz, Idil Erte, Sally John, M. Julia Brosnan, Scott G. Wilson, Loukia Tsaprouni, Ee Mun Lim, Bronwyn G. A. Stuckey, Panos Deloukas, Robert P. Mohney, Karsten Suhre, Tim D. Spector, Ana Maria Valdes · 发表于：International Journal of Epidemiology · 年份：2013 · DOI：10.1093/ije/dyt094 · 被引用次数：293 · 研究领域：Metabolomics and Mass Spectrometry Studies、Epigenetics and DNA Methylation、Birth, Development, and Health

BACKGROUND: Human ageing is a complex, multifactorial process and early developmental factors affect health outcomes in old age. METHODS: Metabolomic profiling on fasting blood was carried out in 6055 individuals from the UK. Stepwise regression was performed to identify a panel of independent metabolites which could be used as a surrogate for age. We also investigated the association with birthweight overall and within identical discordant twins and with genome-wide methylation levels. RESULTS: We identified a panel of 22 metabolites which combined are strongly correlated with age (R(2) = 59%) and with age-related clinical traits independently of age. One particular metabolite, C-glycosyl tryptophan (C-glyTrp), correlated strongly with age (beta = 0.03, SE = 0.001, P = 7.0 × 10(-157)) and lung function (FEV1 beta = -0.04, SE = 0.008, P = 1.8 × 10(-8) adjusted for age and confounders) and was replicated in an independent population (n = 887). C-glyTrp was also associated with bone mineral density (beta = -0.01, SE = 0.002, P = 1.9 × 10(-6)) and birthweight (beta = -0.06, SE = 0.01, P = 2.5 × 10(-9)). The difference in C-glyTrp levels explained 9.4% of the variance in the difference in birthweight between monozygotic twins. An epigenome-wide association study in 172 individuals identified three CpG-sites, associated with levels of C-glyTrp (P < 2 × 10(-6)). We replicated one CpG site in the promoter of the WDR85 gene in an independent sample of 350 individuals (beta = -0.20, S...