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

Zhai, G and Teumer, A and Stolk, L and Perry, JRB and Vandenput, L and Coviello, AD and Koster, A and Bell, JT and Bhasin, S and Eriksson, J and Eriksson, A and Ernst, F and Ferrucci, L and Frayling, TM and Glass, D and Grundberg, E and Haring, R and HedmanÅ, AK and Hofman, A and Kiel, DP and Kroemer, HK and Liu, Y and Lunetta, KL and Maggio, M and Lorentzon, M and Mangino, M and Melzer, D and Miljkovic, I and Nica, A and Penninx, BWJH and Vasan, RS and Rivadeneira, F and Small, KS and Soranzo, N and Uitterlinden, AG and Völzke, H and Wilson, SG and Xi, L and Zhuang, WV and Harris, TB and Murabito, JM and Ohlsson, C and Murray, A and de Jong, FH and Spector, TD and Wallaschofski, H (2011) Eight common genetic variants associated with serum dheas levels suggest a key role in ageing mechanisms. PLoS Genetics, 7 (4). ISSN 1553-7390

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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 = 3.15×10-36), 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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Details

Item Type:	Article
Status:	Published
Creators/Authors:	Creators Email Pitt Username ORCID Zhai, G Teumer, A Stolk, L Perry, JRB Vandenput, L Coviello, AD Koster, A Bell, JT Bhasin, S Eriksson, J Eriksson, A Ernst, F Ferrucci, L Frayling, TM Glass, D Grundberg, E Haring, R HedmanÅ, AK Hofman, A Kiel, DP Kroemer, HK Liu, Y Lunetta, KL Maggio, M Lorentzon, M Mangino, M Melzer, D Miljkovic, I MiljkovicI@edc.pitt.edu IVM1 Nica, A Penninx, BWJH Vasan, RS Rivadeneira, F Small, KS Soranzo, N Uitterlinden, AG Völzke, H Wilson, SG Xi, L Zhuang, WV Harris, TB Murabito, JM Ohlsson, C Murray, A de Jong, FH Spector, TD Wallaschofski, H
Contributors:	Contribution Contributors Name Email Pitt Username ORCID Editor Gibson, Greg UNSPECIFIED UNSPECIFIED UNSPECIFIED
Date:	1 April 2011
Date Type:	Publication
Journal or Publication Title:	PLoS Genetics
Volume:	7
Number:	4
DOI or Unique Handle:	10.1371/journal.pgen.1002025
Schools and Programs:	School of Public Health > Epidemiology
Refereed:	Yes
ISSN:	1553-7390
MeSH Headings:	Actin-Related Protein 2-3 Complex--genetics; Actin-Related Protein 2-3 Complex--metabolism; Adaptor Proteins, Signal Transducing--genetics; Adaptor Proteins, Signal Transducing--metabolism; Adult; Aged; Aging--blood; Aging--genetics; Apoptosis Regulatory Proteins--genetics; Apoptosis Regulatory Proteins--metabolism; Aryl Hydrocarbon Hydroxylases--genetics; Aryl Hydrocarbon Hydroxylases--metabolism; Dehydroepiandrosterone Sulfate--blood; European Continental Ancestry Group--genetics; Female; Gene Expression; Genome-Wide Association Study; Homeodomain Proteins--genetics; Homeodomain Proteins--metabolism; Humans; Kruppel-Like Transcription Factors--genetics; Kruppel-Like Transcription Factors--metabolism; Linkage Disequilibrium; Liver--metabolism; Male; Membrane Proteins--genetics; Membrane Proteins--metabolism; Middle Aged; Polymorphism, Single Nucleotide; Proto-Oncogene Proteins--genetics; Proto-Oncogene Proteins--metabolism; Sulfotransferases--genetics; Sulfotransferases--metabolism; Transcription Factors--genetics; Transcription Factors--metabolism; Young Adult
Other ID:	NLM PMC3077384
PubMed Central ID:	PMC3077384
PubMed ID:	21533175
Date Deposited:	29 Aug 2012 21:15
Last Modified:	22 Jun 2021 15:55
URI:	http://d-scholarship.pitt.edu/id/eprint/13825

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