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

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 developmen...

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Autores principales:	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, MuTHER Consortium, 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
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2011
Materias:	Genetics QH426-470
Acceso en línea:	https://doaj.org/article/47f151fda5224703916d851bbdb3348c
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spelling	oai:doaj.org-article:47f151fda5224703916d851bbdb3348c2021-11-18T06:17:33ZEight common genetic variants associated with serum DHEAS levels suggest a key role in ageing mechanisms.1553-73901553-740410.1371/journal.pgen.1002025https://doaj.org/article/47f151fda5224703916d851bbdb3348c2011-04-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/21533175/pdf/?tool=EBIhttps://doaj.org/toc/1553-7390https://doaj.org/toc/1553-7404Dehydroepiandrosterone 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.Guangju ZhaiAlexander TeumerLisette StolkJohn R B PerryLiesbeth VandenputAndrea D CovielloAnnemarie KosterJordana T BellShalender BhasinJoel ErikssonAnna ErikssonFlorian ErnstLuigi FerrucciTimothy M FraylingDaniel GlassElin GrundbergRobin HaringAsa K HedmanAlbert HofmanDouglas P KielHeyo K KroemerYongmei LiuKathryn L LunettaMarcello MaggioMattias LorentzonMassimo ManginoDavid MelzerIva MiljkovicMuTHER ConsortiumAlexandra NicaBrenda W J H PenninxRamachandran S VasanFernando RivadeneiraKerrin S SmallNicole SoranzoAndré G UitterlindenHenry VölzkeScott G WilsonLi XiWei Vivian ZhuangTamara B HarrisJoanne M MurabitoClaes OhlssonAnna MurrayFrank H de JongTim D SpectorHenri WallaschofskiPublic Library of Science (PLoS)articleGeneticsQH426-470ENPLoS Genetics, Vol 7, Iss 4, p e1002025 (2011)
institution	DOAJ
collection	DOAJ
language	EN
topic	Genetics QH426-470
spellingShingle	Genetics QH426-470 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 MuTHER Consortium 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 Eight common genetic variants associated with serum DHEAS levels suggest a key role in ageing mechanisms.
description	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.
format	article
author	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 MuTHER Consortium 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
author_facet	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 MuTHER Consortium 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
author_sort	Guangju Zhai
title	Eight common genetic variants associated with serum DHEAS levels suggest a key role in ageing mechanisms.
title_short	Eight common genetic variants associated with serum DHEAS levels suggest a key role in ageing mechanisms.
title_full	Eight common genetic variants associated with serum DHEAS levels suggest a key role in ageing mechanisms.
title_fullStr	Eight common genetic variants associated with serum DHEAS levels suggest a key role in ageing mechanisms.
title_full_unstemmed	Eight common genetic variants associated with serum DHEAS levels suggest a key role in ageing mechanisms.
title_sort	eight common genetic variants associated with serum dheas levels suggest a key role in ageing mechanisms.
publisher	Public Library of Science (PLoS)
publishDate	2011
url	https://doaj.org/article/47f151fda5224703916d851bbdb3348c
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Eight common genetic variants associated with serum DHEAS levels suggest a key role in ageing mechanisms.

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