Eight Common Genetic Variants Associated with Serum DHEAS Levels Suggest a Key Role in Ageing Mechanisms

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Eight Common Genetic Variants Associated with Serum DHEAS Levels Suggest a Key Role in Ageing Mechanisms

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Title: Eight Common Genetic Variants Associated with Serum DHEAS Levels Suggest a Key Role in Ageing Mechanisms
Author: Zhai, Guangju; Teumer, Alexander; Stolk, Lisette; Vandenput, Liesbeth; Coviello, Andrea D.; Koster, Annemarie; Bell, Jordana T.; Bhasin, Shalender; Eriksson, Joel; Eriksson, Anna; Ernst, Florian; Ferrucci, Luigi; Frayling, Timothy M.; Grundberg, Elin; Haring, Robin; Kroemer, Heyo K.; Liu, Yongmei; Lunetta, Kathryn L.; Maggio, Marcello; Lorentzon, Mattias; Mangino, Massimo; Melzer, David; Miljkovic, Iva; Nica, Alexandra; Penninx, Brenda W. J. H.; Vasan, Ramachandran S.; Rivadeneira, Fernando; Small, Kerrin S.; Soranzo, Nicole; Xi, Li; Zhuang, Wei Vivian; Harris, Tamara B.; Murabito, Joanne M.; Ohlsson, Claes; Murray, Anna; de Jong, Frank H.; Spector, Tim D.; Wallaschofski, Henri; Perry, John; Wilson, Scott G.; Glass, Daniel; Hofman, Albert; Kiel, Douglas P.; Hedman, Asa K.; Uitterlinden, Andre G.; Volzke, Henry

Note: Order does not necessarily reflect citation order of authors.

Citation: Zhai, Guangju, Alexander Teumer, Lisette Stolk, John R. B. Perry, Liesbeth Vandenput, Andrea D. Coviello, Annemarie Koster, et al. 2011. Eight common genetic variants associated with serum DHEAS levels suggest a key role in ageing mechanisms. PLoS Genetics 7(4): e1002025.
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Abstract: Dehydroepiandrosterone sulphate (DHEAS) is the most abundant circulating steroid secreted by adrenal glands, yet its function is unknown. Its serum concentration declines significantly with increasing age, which has led to speculation that a relative DHEAS deficiency may contribute to the development of common age-related diseases or diminished longevity. We conducted a meta-analysis of genome-wide association data with 14,846 individuals and identified eight independent common SNPs associated with serum DHEAS concentrations. Genes at or near the identified loci include ZKSCAN5 (rs11761528; p = 3.15610236), SULT2A1 (rs2637125; p = 2.61610219), ARPC1A (rs740160; p = 1.56610216), TRIM4 (rs17277546; p = 4.50610211), BMF (rs7181230; p = 5.44610211), HHEX (rs2497306; p = 4.6461029), BCL2L11 (rs6738028; p = 1.7261028), and CYP2C9 (rs2185570; p = 2.2961028). These genes are associated with type 2 diabetes, lymphoma, actin filament assembly, drug and xenobiotic metabolism, and zinc finger proteins. Several SNPs were associated with changes in gene expression levels, and the related genes are connected to biological pathways linking DHEAS with ageing. This study provides much needed insight into the function of DHEAS.
Published Version: doi:10.1371/journal.pgen.1002025
Other Sources: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3077384/pdf/
Terms of Use: This article is made available under the terms and conditions applicable to Other Posted Material, as set forth at http://nrs.harvard.edu/urn-3:HUL.InstRepos:dash.current.terms-of-use#LAA
Citable link to this page: http://nrs.harvard.edu/urn-3:HUL.InstRepos:5146966
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