Journal
PLOS GENETICS
Volume 7, Issue 4, Pages -Publisher
PUBLIC LIBRARY SCIENCE
DOI: 10.1371/journal.pgen.1002025
Keywords
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Categories
Funding
- Wellcome Trust
- Arthritis Research Campaign
- European Community [HEALTH-F2-2008-201865-GEFOS, HEALTH-F4-2007-201413, QLG2-CT-2002-01254]
- UK Department of Health via the National Institute for Health Research (NIHR)
- Biotechnology and Biological Sciences Research Council [G20234]
- National Eye Institute (NEI) via an NIH/Center for Inherited Disease Research (CIDR)
- Federal Ministry of Education and Research [01ZZ9603, 01ZZ0103, 01ZZ0403, 03ZIK012]
- Ministry of Cultural Affairs
- Social Ministry of the Federal State of Mecklenburg West Pomerania
- Siemens Healthcare, Erlangen, Germany
- Federal State of Mecklenburg West Pomerania
- Ministry of Cultural Affairs of the Federal State of Mecklenburg - West Pomerania [03IS2061A]
- Siemens Healthcare Diagnostics, Eschborn
- DPC Biermann GmbH, Bad Nauheim, Germany
- Novo Nordisc
- National Institute on Aging [N01-AG-6-2101, N01-AG-6-2103, N01-AG-6-2106]
- NIA [1R01AG032098-01A1]
- National Institutes of Health [HHSN268200782096C]
- NIH, National Institute on Aging
- Netherlands Organisation of Scientific Research NWO [175.010.2005.011, 911-03-012]
- Research Institute for Diseases in the Elderly (RIDE2) [014-93-015]
- Netherlands Genomics Initiative (NGI) Netherlands Consortium of Healthy Aging (NCHA) [050-060-810]
- European Commision [HEALTH-F2-2008-201865, HEALTH-F2-2008-35627]
- Erasmus Medical Center
- Erasmus University, Rotterdam
- Netherlands Organization for the Health Research and Development (ZonMw)
- Research Institute for Diseases in the Elderly (RIDE)
- Ministry of Education, Culture and Science
- Ministry for Health, Welfare and Sports
- European Commission [HEALTH-F2-2008-201865-GEFOS]
- Municipality of Rotterdam
- German Bundesministerium fuer Forschung und Technology [01 AK 803 A-H, 01 IG 07015 G]
- National Institute of Aging [R21AG032598]
- National Heart, Lung and Blood Institute [N01-HC-25195]
- Affymetrix, Inc [N02-HL-6-4278]
- Robert Dawson Evans Endowment of the Department of Medicine at Boston University School of Medicine and Boston Medical Center
- NIH [R01 AR/AG 41398]
- Swedish Research Council [K2010-54X-09894-19-3, 2006-3832]
- Swedish Foundation for Strategic Research
- ALF/LUA
- Lundberg Foundation
- Torsten and Ragnar Soderberg's Foundation
- Petrus and Augusta Hedlunds Foundation
- Vastra Gotaland Foundation
- Goteborg Medical Society
- Novo Nordisk foundation
- Italian Ministry of Health [ICS110.1/RF97.71]
- U.S. National Institute on Aging [263 MD 9164, 263 MD 821336, N.1-AG-1-1, N.1-AG-1-2111, N01-AG-5-0002]
- National Institute on Aging, National Institutes of Health, Baltimore, Maryland
- Sir Henry Wellcome Postdoctoral Fellowship [092447/Z/10/Z]
- MRC [G0900339] Funding Source: UKRI
- Wellcome Trust [092447/Z/10/Z] Funding Source: Wellcome Trust
- Medical Research Council [G0900339] Funding Source: researchfish
- Versus Arthritis [17489] Funding Source: researchfish
Ask authors/readers for more resources
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 = 3.15610(-36)), SULT2A1 (rs2637125; p = 2.61610(-19)), ARPC1A (rs740160; p = 1.56610(-16)), TRIM4 (rs17277546; p = 4.50610(-11)), BMF (rs7181230; p = 5.44610(-11)), HHEX (rs2497306; p = 4.64610(-9)), BCL2L11 ( rs6738028; p = 1.72610(-8)), and CYP2C9 (rs2185570; p = 2.29610(-8)). 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.
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