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Reference: Zhai, G, Teumer, A, Stolk, L et al., (2011). Eight common genetic variants associated with serum DHEAS levels suggest a key role in ageing mechanisms. PLoS genetics, 7 (4), e1002025.Citable link to this page:


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

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.

Peer Review status:Peer reviewedPublication status:PublishedVersion:Publisher's version Funder: Wellcome Trust   Funder: Arthritis Research Campaign   Funder: European Community's Seventh Framework Programme   Funder: ENGAGE   Funder: FP-5 GenomEUtwin Project   Funder: UK Department of Health   Funder: Biotechnology and Biological Sciences Research Council   Funder: UK Department of Health   Funder: National Eye Institute   Funder: Federal Ministry of Education and Research   Funder: Siemens Healthcare   Funder: Federal State of Mecklenburg West Pomerania   Funder: Novo Nordisk   Funder: National Institute on Aging   Funder: Center for Inherited Disease Research   Funder: Netherlands Organisation of Scientific Research   Funder: Research Institute for Diseases in the Elderly   Funder: Netherlands Genomics Initiative   Funder: European Commision   Funder: Erasmus Medical Center   Funder: Netherlands Organization for the Health Research and Development   Funder: Research Institute for Diseases in the Elderly   Funder: Ministry of Education, Culture and Science   Funder: Ministry for Health, Welfare and Sports   Funder: European Commission   Funder: Municipality of Rotterdam   Funder: National Heart, Lung and Blood Institute   Funder: Swedish Research Council   Funder: Swedish Foundation for Strategic Research   Funder: ALF/LUA   Funder: Lundberg Foundation   Funder: Torsten and Ragnar Soderberg's Foundation   Funder: Petrus and Augusta Hedlunds Foundation   Funder: Vastra Gotaland Foundation   Funder: Goteborg Medical Society   Funder: German Bundesministerium fuer Forschung und Technology   Funder: Italian Ministry of Health   Notes:This is an open-access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication.

Bibliographic Details

Publisher: Public Library of Science

Publisher Website: http://www.plos.org

Journal: PLoS geneticssee more from them

Publication Website: http://www.plosgenetics.org

Issue Date: 2011-4

pages:Article: e1002025


Urn: uuid:75cc8eb6-3abe-48f4-99ea-aa193873e989

Source identifier: 146593

Eissn: 1553-7404

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

Issn: 1553-7390 Item Description

Type: Journal article;

Language: eng

Version: Publisher's versionKeywords: MuTHER Consortium Humans Liver Aryl Hydrocarbon Hydroxylases Dehydroepiandrosterone Sulfate Adaptor Proteins, Signal Transducing Transcription Factors Sulfotransferases Homeodomain Proteins Membrane Proteins Proto-Oncogene Proteins Aging Linkage Disequilibrium Gene Expression European Continental Ancestry Group Adult Aged Kruppel-Like Transcription Factors Middle Aged Genome-Wide Association Study Young Adult Polymorphism, Single Nucleotide Female Apoptosis Regulatory Proteins Male Actin-Related Protein 2-3 Complex Tiny URL: pubs:146593


Author: Zhai, G - - - Teumer, A - - - Stolk, L - - - Perry, JR - - - Vandenput, L - - - Coviello, AD - - - Koster, A - - - Bell, JT - ins

Source: https://ora.ox.ac.uk/objects/uuid:75cc8eb6-3abe-48f4-99ea-aa193873e989


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