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. KielHeyo 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

Research output: Contribution to journalArticle

55 Citations (Scopus)

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.

Original languageEnglish
Article numbere1002025
JournalPLoS Genetics
Volume7
Issue number4
DOIs
StatePublished - Apr 2011
Externally publishedYes

Fingerprint

prasterone
Dehydroepiandrosterone Sulfate
serum
sulfate
Serum
Single Nucleotide Polymorphism
gene
Genes
genes
diabetes
zinc finger motif
adrenal glands
Zinc Fingers
meta-analysis
Xenobiotics
xenobiotics
steroid
Adrenal Glands
lymphoma
microfilaments

All Science Journal Classification (ASJC) codes

  • Genetics
  • Molecular Biology
  • Ecology, Evolution, Behavior and Systematics
  • Cancer Research
  • Genetics(clinical)

Cite this

Zhai, G., Teumer, A., Stolk, L., Perry, J. R. B., Vandenput, L., Coviello, A. D., ... Wallaschofski, H. (2011). Eight common genetic variants associated with serum dheas levels suggest a key role in ageing mechanisms. PLoS Genetics, 7(4), [e1002025]. https://doi.org/10.1371/journal.pgen.1002025

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; Eriksson, Anna; Ernst, Florian; Ferrucci, Luigi; Frayling, Timothy M.; Glass, Daniel; Grundberg, Elin; Haring, Robin; HedmanÅ, 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; 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.

In: PLoS Genetics, Vol. 7, No. 4, e1002025, 04.2011.

Research output: Contribution to journalArticle

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, ÅK, Hofman, A, Kiel, DP, Kroemer, HK, Liu, Y, Lunetta, KL, Maggio, M, Lorentzon, M, Mangino, M, Melzer, D, Miljkovic, I, 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 2011, 'Eight common genetic variants associated with serum dheas levels suggest a key role in ageing mechanisms', PLoS Genetics, vol. 7, no. 4, e1002025. https://doi.org/10.1371/journal.pgen.1002025
Zhai, Guangju ; Teumer, Alexander ; Stolk, Lisette ; Perry, John R B ; Vandenput, Liesbeth ; Coviello, Andrea D. ; Koster, Annemarie ; Bell, Jordana T. ; Bhasin, Shalender ; Eriksson, Joel ; Eriksson, Anna ; Ernst, Florian ; Ferrucci, Luigi ; Frayling, Timothy M. ; Glass, Daniel ; Grundberg, Elin ; Haring, Robin ; HedmanÅ, 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 ; 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. / Eight common genetic variants associated with serum dheas levels suggest a key role in ageing mechanisms. In: PLoS Genetics. 2011 ; Vol. 7, No. 4.
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AU - Coviello, Andrea D.

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AU - Kiel, Douglas P.

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AU - Liu, Yongmei

AU - Lunetta, Kathryn L.

AU - Maggio, Marcello

AU - Lorentzon, Mattias

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AU - Miljkovic, Iva

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AU - Uitterlinden, André G.

AU - Völzke, Henry

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AU - Xi, Li

AU - Zhuang, Wei Vivian

AU - Harris, Tamara B.

AU - Murabito, Joanne M.

AU - Ohlsson, Claes

AU - Murray, Anna

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