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; Asa K. Hedman; 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; Andre G. Uitterlinden; Henry Voelzke; 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

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, Asa K. Hedman, 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, Andre G. Uitterlinden, Henry Voelzke, 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

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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 = 3.15610(-36)), SULT2A1 (rs2637125; p = 2.61610(-19)), ARPC1A (rs740160; p = 1.56610(-16)), TRIM4 (rs17277546; p = 4.50610(-11)), BMF (rs7181230; p = 5.44610(-11)), HHEX (rs2497306; p = 4.64610(-9)), BCL2L11 ( rs6738028; p = 1.72610(-8)), and CYP2C9 (rs2185570; p = 2.29610(-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 language	English
Article number	e1002025
Journal	PL o S Genetics
Volume	7
Issue number	4
Publication status	Published - Apr 2011

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Zhai, G., Teumer, A., Stolk, L., Perry, J. R. B., Vandenput, L., Coviello, A. D., Koster, A., Bell, J. T., Bhasin, S., Eriksson, J., Eriksson, A., Ernst, F., Ferrucci, L., Frayling, T. M., Glass, D., Grundberg, E., Haring, R., Hedman, A. K., Hofman, A., ... Wallaschofski, H. (2011). Eight Common Genetic Variants Associated with Serum DHEAS Levels Suggest a Key Role in Ageing Mechanisms. PL o S Genetics, 7(4), Article e1002025.

@article{37814f22e5754edcae69fb840ebd6148,

title = "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 = 3.15610(-36)), SULT2A1 (rs2637125; p = 2.61610(-19)), ARPC1A (rs740160; p = 1.56610(-16)), TRIM4 (rs17277546; p = 4.50610(-11)), BMF (rs7181230; p = 5.44610(-11)), HHEX (rs2497306; p = 4.64610(-9)), BCL2L11 ( rs6738028; p = 1.72610(-8)), and CYP2C9 (rs2185570; p = 2.29610(-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.",

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

year = "2011",

month = apr,

language = "English",

volume = "7",

journal = "PL o S Genetics",

issn = "1553-7404",

publisher = "Public Library of Science",

number = "4",

}

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, Hedman, AK, 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, Voelzke, 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', PL o S Genetics, vol. 7, no. 4, e1002025.

TY - JOUR

T1 - Eight Common Genetic Variants Associated with Serum DHEAS Levels Suggest a Key Role in Ageing Mechanisms

AU - Zhai, Guangju

AU - Teumer, Alexander

AU - Stolk, Lisette

AU - Perry, John R. B.

AU - Vandenput, Liesbeth

AU - Coviello, Andrea D.

AU - Koster, Annemarie

AU - Bell, Jordana T.

AU - Bhasin, Shalender

AU - Eriksson, Joel

AU - Eriksson, Anna

AU - Ernst, Florian

AU - Ferrucci, Luigi

AU - Frayling, Timothy M.

AU - Glass, Daniel

AU - Grundberg, Elin

AU - Haring, Robin

AU - Hedman, Asa K.

AU - Hofman, Albert

AU - Kiel, Douglas P.

AU - Kroemer, Heyo K.

AU - Liu, Yongmei

AU - Lunetta, Kathryn L.

AU - Maggio, Marcello

AU - Lorentzon, Mattias

AU - Mangino, Massimo

AU - Melzer, David

AU - Miljkovic, Iva

AU - Nica, Alexandra

AU - Penninx, Brenda W. J. H.

AU - Vasan, Ramachandran S.

AU - Rivadeneira, Fernando

AU - Small, Kerrin S.

AU - Soranzo, Nicole

AU - Uitterlinden, Andre G.

AU - Voelzke, Henry

AU - Wilson, Scott G.

AU - Xi, Li

AU - Zhuang, Wei Vivian

AU - Harris, Tamara B.

AU - Murabito, Joanne M.

AU - Ohlsson, Claes

AU - Murray, Anna

AU - de Jong, Frank H.

AU - Spector, Tim D.

AU - Wallaschofski, Henri

PY - 2011/4

Y1 - 2011/4

N2 - 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 = 3.15610(-36)), SULT2A1 (rs2637125; p = 2.61610(-19)), ARPC1A (rs740160; p = 1.56610(-16)), TRIM4 (rs17277546; p = 4.50610(-11)), BMF (rs7181230; p = 5.44610(-11)), HHEX (rs2497306; p = 4.64610(-9)), BCL2L11 ( rs6738028; p = 1.72610(-8)), and CYP2C9 (rs2185570; p = 2.29610(-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.

AB - 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 = 3.15610(-36)), SULT2A1 (rs2637125; p = 2.61610(-19)), ARPC1A (rs740160; p = 1.56610(-16)), TRIM4 (rs17277546; p = 4.50610(-11)), BMF (rs7181230; p = 5.44610(-11)), HHEX (rs2497306; p = 4.64610(-9)), BCL2L11 ( rs6738028; p = 1.72610(-8)), and CYP2C9 (rs2185570; p = 2.29610(-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.

M3 - Article

SN - 1553-7404

VL - 7

JO - PL o S Genetics

JF - PL o S Genetics

IS - 4

M1 - e1002025

ER -

Eight Common Genetic Variants Associated with Serum DHEAS Levels Suggest a Key Role in Ageing Mechanisms

Abstract

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