Eight common genetic variants associated with serum dheas levels suggest a key role in ageing mechanisms

Guangju Zhai; Alexander Teumer; Lisette Stolk; John R.B. Perry; Liesbeth Vandenput; Andrea D. Coviello; Annemarie Koster; Jordana T. Bell; Shalender Bhasin; Joel Eriksson; Anna Eriksson; Florian Ernst; Luigi Ferrucci; Timothy M. Frayling; Daniel Glass; Elin Grundberg; Robin Haring; Åsa K. HedmanÅ; Albert Hofman; Douglas P. Kiel; Heyo K. Kroemer; Yongmei Liu; Kathryn L. Lunetta; Marcello Maggio; Mattias Lorentzon; Massimo Mangino; David Melzer; Iva Miljkovic; Alexandra Nica; Brenda W.J.H. Penninx; Ramachandran S. Vasan; Fernando Rivadeneira; Kerrin S. Small; Nicole Soranzo; André G. Uitterlinden; Henry Völzke; Scott G. Wilson; Li Xi; Wei Vivian Zhuang; Tamara B. Harris; Joanne M. Murabito; Claes Ohlsson; Anna Murray; Frank H. de Jong; Tim D. Spector; Henri Wallaschofski

doi:10.1371/journal.pgen.1002025

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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

Guangju Zhai, Alexander Teumer, Lisette Stolk, John R.B. Perry, Liesbeth Vandenput, Andrea D. Coviello, Annemarie Koster, Jordana T. Bell, Shalender Bhasin, Joel Eriksson, …

PLoS genetics, Vol.7(4), e1002025

04/2011

DOI: https://doi.org/10.1371/journal.pgen.1002025

PMCID: PMC3077384

PMID: 21533175

Abstract

Ecology, Evolution, Behavior and Systematics

Molecular Biology

Genetics

Genetics(clinical)

Cancer Research

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.

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Title: Eight common genetic variants associated with serum dheas levels suggest a key role in ageing mechanisms
Creators: Guangju Zhai (Author) - King's College London
Alexander Teumer (Author) - University of Greifswald
Lisette Stolk (Author) - Erasmus University Rotterdam;Netherlands Consortium of Healthy Ageing
John R.B. Perry (Author) - University of Exeter;University of Oxford
Liesbeth Vandenput (Author) - University of Gothenburg
Andrea D. Coviello (Author) - Boston University
Annemarie Koster (Author) - National Institutes of Health
Jordana T. Bell (Author) - King's College London;University of Oxford
Shalender Bhasin (Author) - Boston University
Joel Eriksson (Author) - University of Gothenburg
Anna Eriksson (Author) - University of Gothenburg
Florian Ernst (Author) - University of Greifswald
Luigi Ferrucci (Author) - National Institutes of Health
Timothy M. Frayling (Author) - University of Exeter
Daniel Glass (Author) - King's College London
Elin Grundberg (Author) - King's College London;Wellcome Sanger Institute
Robin Haring (Author) - University of Greifswald
Åsa K. HedmanÅ (Author) - University of Oxford
Albert Hofman (Author) - Netherlands Consortium of Healthy Ageing;Erasmus University Rotterdam
Douglas P. Kiel (Author) - Harvard University
Heyo K. Kroemer (Author) - University of Greifswald
Yongmei Liu (Author) - Wake Forest University
Kathryn L. Lunetta (Author) - Boston University
Marcello Maggio (Author) - University of Parma
Mattias Lorentzon (Author) - University of Gothenburg
Massimo Mangino (Author) - King's College London
David Melzer (Author) - University of Exeter
Iva Miljkovic (Author) - University of Pittsburgh
Alexandra Nica (Author) - Wellcome Sanger Institute;University of Geneva
Brenda W.J.H. Penninx (Author) - VU Medical Center
Ramachandran S. Vasan (Author) - Boston University;National Heart, Lung, and Blood Institute's The Framingham Heart Study
Fernando Rivadeneira (Author) - Erasmus University Rotterdam;Netherlands Consortium of Healthy Ageing
Kerrin S. Small (Author) - King's College London;Wellcome Sanger Institute
Nicole Soranzo (Author) - King's College London;Wellcome Sanger Institute
André G. Uitterlinden (Author) - Erasmus University Rotterdam;Netherlands Consortium of Healthy Ageing
Henry Völzke (Author) - University of Greifswald
Scott G. Wilson (Author) - King's College London;Sir Charles Gairdner Hospital;University of Western Australia
Li Xi (Author) - Pfizer
Wei Vivian Zhuang (Author) - Public Health
Tamara B. Harris (Author) - National Institutes of Health
Joanne M. Murabito (Author) - Boston University;National Heart, Lung, and Blood Institute's The Framingham Heart Study
Claes Ohlsson (Author) - University of Gothenburg
Anna Murray (Author) - University of Exeter
Frank H. de Jong (Author) - Erasmus University Rotterdam
Tim D. Spector (Author) - King's College London
Henri Wallaschofski (Author) - University of Greifswald
Publication Details: PLoS genetics, Vol.7(4), e1002025
Series: 7
Identifiers: 991005928635102656
Academic Unit: Master Public Health
Language: English
Resource Type: Journal article