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Eight common genetic variants associated with serum DHEAS levels suggest a key role in ageing mechanisms
Zhai, Guangju Teumer, Alexander Stolk, Lisette Perry, John R. B. Vandenput, Liesbeth Coviello, Andrea D. Koster, Annemarie Bell, Jordana T. Bhasin, Shalender Eriksson, Joel
Zhai, Guangju
Teumer, Alexander
Stolk, Lisette
Perry, John R. B.
Vandenput, Liesbeth
Coviello, Andrea D.
Koster, Annemarie
Bell, Jordana T.
Bhasin, Shalender
Eriksson, Joel
Author
Zhai, Guangju
Teumer, Alexander
Stolk, Lisette
Perry, John R. B.
Vandenput, Liesbeth
Coviello, Andrea D.
Koster, Annemarie
Bell, Jordana T.
Bhasin, Shalender
Eriksson, Joel
Ernst, Florian
Ferrucci, Luigi
Frayling, Timothy M.
Glass, Daniel
Grundberg, Elin
Haring, Robin
Hedman, Åsa K.
Hofman, Albert
Kiel, Douglas P.
Kroemer, Heyo K.
Liu, Yongmei
Lunetta, Kathryn L.
Maggio, Marcello
Lorentzon, Mattias
Mangino, Massimo
Melzer, David
Miljkovic, Iva
MuTHER Consortium,
Nica, Alexandra
Penninx, Brenda W. J. H.
Vasan, Ramachandran S.
Rivadeneira, Fernando
Small, Kerrin S.
Soranzo, Nicole
Uitterlinden, André G.
Völzke, Henry
Wilson, Scott G.
Xi, Li
Zhuang, Wei Vivian
Harris, Tamara B.
Murabito, Joanne M.
Ohlsson, Claes
Murray, Anna
de Jong, Frank H.
Spector, Tim D.
Wallaschofski, Henri
Eriksson, Anna L.
MuTHER Consortium
Teumer, Alexander
Stolk, Lisette
Perry, John R. B.
Vandenput, Liesbeth
Coviello, Andrea D.
Koster, Annemarie
Bell, Jordana T.
Bhasin, Shalender
Eriksson, Joel
Ernst, Florian
Ferrucci, Luigi
Frayling, Timothy M.
Glass, Daniel
Grundberg, Elin
Haring, Robin
Hedman, Åsa K.
Hofman, Albert
Kiel, Douglas P.
Kroemer, Heyo K.
Liu, Yongmei
Lunetta, Kathryn L.
Maggio, Marcello
Lorentzon, Mattias
Mangino, Massimo
Melzer, David
Miljkovic, Iva
MuTHER Consortium,
Nica, Alexandra
Penninx, Brenda W. J. H.
Vasan, Ramachandran S.
Rivadeneira, Fernando
Small, Kerrin S.
Soranzo, Nicole
Uitterlinden, André G.
Völzke, Henry
Wilson, Scott G.
Xi, Li
Zhuang, Wei Vivian
Harris, Tamara B.
Murabito, Joanne M.
Ohlsson, Claes
Murray, Anna
de Jong, Frank H.
Spector, Tim D.
Wallaschofski, Henri
Eriksson, Anna L.
MuTHER Consortium
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 = 3.15×10−36), SULT2A1 (rs2637125; p = 2.61×10−19), ARPC1A (rs740160; p = 1.56×10−16), TRIM4 (rs17277546; p = 4.50×10−11), BMF (rs7181230; p = 5.44×10−11), HHEX (rs2497306; p = 4.64×10−9), BCL2L11 (rs6738028; p = 1.72×10−8), and CYP2C9 (rs2185570; p = 2.29×10−8). 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.
Keywords
Date
2011
Type
Journal article
Journal
PLoS Genetics
Book
Volume
7
Issue
4
Page Range
1-10
Article Number
ACU Department
Mary MacKillop Institute for Health Research
Faculty of Health Sciences
Faculty of Health Sciences
Collections
Relation URI
Source URL
Event URL
Open Access Status
Open access
License
File Access
Open