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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Public Library of Science (PLoS)
2011-04-01
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| Series: | PLoS Genetics |
| Online Access: | https://doi.org/10.1371/journal.pgen.1002025 |
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| 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 |
| collection | DOAJ |
| 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 |
| id | doaj-art-47f151fda5224703916d851bbdb3348c |
| institution | DOAJ |
| issn | 1553-7390 1553-7404 |
| language | English |
| publishDate | 2011-04-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS Genetics |
| spelling | doaj-art-47f151fda5224703916d851bbdb3348c2025-08-20T03:10:22ZengPublic Library of Science (PLoS)PLoS Genetics1553-73901553-74042011-04-0174e100202510.1371/journal.pgen.1002025Eight common genetic variants associated with serum DHEAS levels suggest a key role in ageing mechanisms.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 WallaschofskiDehydroepiandrosterone 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.https://doi.org/10.1371/journal.pgen.1002025 |
| spellingShingle | 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. PLoS Genetics |
| title | 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_short | 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 |
| url | https://doi.org/10.1371/journal.pgen.1002025 |
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