Genetic determinants of serum testosterone concentrations in men.
Testosterone concentrations in men are associated with cardiovascular morbidity, osteoporosis, and mortality and are affected by age, smoking, and obesity. Because of serum testosterone's high heritability, we performed a meta-analysis of genome-wide association data in 8,938 men from seven coh...
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Public Library of Science (PLoS)
2011-10-01
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| Series: | PLoS Genetics |
| Online Access: | https://journals.plos.org/plosgenetics/article/file?id=10.1371/journal.pgen.1002313&type=printable |
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| author | Claes Ohlsson Henri Wallaschofski Kathryn L Lunetta Lisette Stolk John R B Perry Annemarie Koster Ann-Kristin Petersen Joel Eriksson Terho Lehtimäki Ilpo T Huhtaniemi Geoffrey L Hammond Marcello Maggio Andrea D Coviello EMAS Study Group Luigi Ferrucci Margit Heier Albert Hofman Kate L Holliday John-Olov Jansson Mika Kähönen David Karasik Magnus K Karlsson Douglas P Kiel Yongmei Liu Osten Ljunggren Mattias Lorentzon Leo-Pekka Lyytikäinen Thomas Meitinger Dan Mellström David Melzer Iva Miljkovic Matthias Nauck Maria Nilsson Brenda Penninx Stephen R Pye Ramachandran S Vasan Martin Reincke Fernando Rivadeneira Abdelouahid Tajar Alexander Teumer André G Uitterlinden Jagadish Ulloor Jorma Viikari Uwe Völker Henry Völzke H Erich Wichmann Tsung-Sheng Wu Wei Vivian Zhuang Elad Ziv Frederick C W Wu Olli Raitakari Anna Eriksson Martin Bidlingmaier Tamara B Harris Anna Murray Frank H de Jong Joanne M Murabito Shalender Bhasin Liesbeth Vandenput Robin Haring |
| author_facet | Claes Ohlsson Henri Wallaschofski Kathryn L Lunetta Lisette Stolk John R B Perry Annemarie Koster Ann-Kristin Petersen Joel Eriksson Terho Lehtimäki Ilpo T Huhtaniemi Geoffrey L Hammond Marcello Maggio Andrea D Coviello EMAS Study Group Luigi Ferrucci Margit Heier Albert Hofman Kate L Holliday John-Olov Jansson Mika Kähönen David Karasik Magnus K Karlsson Douglas P Kiel Yongmei Liu Osten Ljunggren Mattias Lorentzon Leo-Pekka Lyytikäinen Thomas Meitinger Dan Mellström David Melzer Iva Miljkovic Matthias Nauck Maria Nilsson Brenda Penninx Stephen R Pye Ramachandran S Vasan Martin Reincke Fernando Rivadeneira Abdelouahid Tajar Alexander Teumer André G Uitterlinden Jagadish Ulloor Jorma Viikari Uwe Völker Henry Völzke H Erich Wichmann Tsung-Sheng Wu Wei Vivian Zhuang Elad Ziv Frederick C W Wu Olli Raitakari Anna Eriksson Martin Bidlingmaier Tamara B Harris Anna Murray Frank H de Jong Joanne M Murabito Shalender Bhasin Liesbeth Vandenput Robin Haring |
| author_sort | Claes Ohlsson |
| collection | DOAJ |
| description | Testosterone concentrations in men are associated with cardiovascular morbidity, osteoporosis, and mortality and are affected by age, smoking, and obesity. Because of serum testosterone's high heritability, we performed a meta-analysis of genome-wide association data in 8,938 men from seven cohorts and followed up the genome-wide significant findings in one in silico (n = 871) and two de novo replication cohorts (n = 4,620) to identify genetic loci significantly associated with serum testosterone concentration in men. All these loci were also associated with low serum testosterone concentration defined as <300 ng/dl. Two single-nucleotide polymorphisms at the sex hormone-binding globulin (SHBG) locus (17p13-p12) were identified as independently associated with serum testosterone concentration (rs12150660, p = 1.2×10(-41) and rs6258, p = 2.3×10(-22)). Subjects with ≥ 3 risk alleles of these variants had 6.5-fold higher risk of having low serum testosterone than subjects with no risk allele. The rs5934505 polymorphism near FAM9B on the X chromosome was also associated with testosterone concentrations (p = 5.6×10(-16)). The rs6258 polymorphism in exon 4 of SHBG affected SHBG's affinity for binding testosterone and the measured free testosterone fraction (p<0.01). Genetic variants in the SHBG locus and on the X chromosome are associated with a substantial variation in testosterone concentrations and increased risk of low testosterone. rs6258 is the first reported SHBG polymorphism, which affects testosterone binding to SHBG and the free testosterone fraction and could therefore influence the calculation of free testosterone using law-of-mass-action equation. |
| format | Article |
| id | doaj-art-5e1b69b3dd67477b8f3c8991cffe202d |
| institution | OA Journals |
| issn | 1553-7390 1553-7404 |
| language | English |
| publishDate | 2011-10-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS Genetics |
| spelling | doaj-art-5e1b69b3dd67477b8f3c8991cffe202d2025-08-20T02:30:55ZengPublic Library of Science (PLoS)PLoS Genetics1553-73901553-74042011-10-01710e100231310.1371/journal.pgen.1002313Genetic determinants of serum testosterone concentrations in men.Claes OhlssonHenri WallaschofskiKathryn L LunettaLisette StolkJohn R B PerryAnnemarie KosterAnn-Kristin PetersenJoel ErikssonTerho LehtimäkiIlpo T HuhtaniemiGeoffrey L HammondMarcello MaggioAndrea D CovielloEMAS Study GroupLuigi FerrucciMargit HeierAlbert HofmanKate L HollidayJohn-Olov JanssonMika KähönenDavid KarasikMagnus K KarlssonDouglas P KielYongmei LiuOsten LjunggrenMattias LorentzonLeo-Pekka LyytikäinenThomas MeitingerDan MellströmDavid MelzerIva MiljkovicMatthias NauckMaria NilssonBrenda PenninxStephen R PyeRamachandran S VasanMartin ReinckeFernando RivadeneiraAbdelouahid TajarAlexander TeumerAndré G UitterlindenJagadish UlloorJorma ViikariUwe VölkerHenry VölzkeH Erich WichmannTsung-Sheng WuWei Vivian ZhuangElad ZivFrederick C W WuOlli RaitakariAnna ErikssonMartin BidlingmaierTamara B HarrisAnna MurrayFrank H de JongJoanne M MurabitoShalender BhasinLiesbeth VandenputRobin HaringTestosterone concentrations in men are associated with cardiovascular morbidity, osteoporosis, and mortality and are affected by age, smoking, and obesity. Because of serum testosterone's high heritability, we performed a meta-analysis of genome-wide association data in 8,938 men from seven cohorts and followed up the genome-wide significant findings in one in silico (n = 871) and two de novo replication cohorts (n = 4,620) to identify genetic loci significantly associated with serum testosterone concentration in men. All these loci were also associated with low serum testosterone concentration defined as <300 ng/dl. Two single-nucleotide polymorphisms at the sex hormone-binding globulin (SHBG) locus (17p13-p12) were identified as independently associated with serum testosterone concentration (rs12150660, p = 1.2×10(-41) and rs6258, p = 2.3×10(-22)). Subjects with ≥ 3 risk alleles of these variants had 6.5-fold higher risk of having low serum testosterone than subjects with no risk allele. The rs5934505 polymorphism near FAM9B on the X chromosome was also associated with testosterone concentrations (p = 5.6×10(-16)). The rs6258 polymorphism in exon 4 of SHBG affected SHBG's affinity for binding testosterone and the measured free testosterone fraction (p<0.01). Genetic variants in the SHBG locus and on the X chromosome are associated with a substantial variation in testosterone concentrations and increased risk of low testosterone. rs6258 is the first reported SHBG polymorphism, which affects testosterone binding to SHBG and the free testosterone fraction and could therefore influence the calculation of free testosterone using law-of-mass-action equation.https://journals.plos.org/plosgenetics/article/file?id=10.1371/journal.pgen.1002313&type=printable |
| spellingShingle | Claes Ohlsson Henri Wallaschofski Kathryn L Lunetta Lisette Stolk John R B Perry Annemarie Koster Ann-Kristin Petersen Joel Eriksson Terho Lehtimäki Ilpo T Huhtaniemi Geoffrey L Hammond Marcello Maggio Andrea D Coviello EMAS Study Group Luigi Ferrucci Margit Heier Albert Hofman Kate L Holliday John-Olov Jansson Mika Kähönen David Karasik Magnus K Karlsson Douglas P Kiel Yongmei Liu Osten Ljunggren Mattias Lorentzon Leo-Pekka Lyytikäinen Thomas Meitinger Dan Mellström David Melzer Iva Miljkovic Matthias Nauck Maria Nilsson Brenda Penninx Stephen R Pye Ramachandran S Vasan Martin Reincke Fernando Rivadeneira Abdelouahid Tajar Alexander Teumer André G Uitterlinden Jagadish Ulloor Jorma Viikari Uwe Völker Henry Völzke H Erich Wichmann Tsung-Sheng Wu Wei Vivian Zhuang Elad Ziv Frederick C W Wu Olli Raitakari Anna Eriksson Martin Bidlingmaier Tamara B Harris Anna Murray Frank H de Jong Joanne M Murabito Shalender Bhasin Liesbeth Vandenput Robin Haring Genetic determinants of serum testosterone concentrations in men. PLoS Genetics |
| title | Genetic determinants of serum testosterone concentrations in men. |
| title_full | Genetic determinants of serum testosterone concentrations in men. |
| title_fullStr | Genetic determinants of serum testosterone concentrations in men. |
| title_full_unstemmed | Genetic determinants of serum testosterone concentrations in men. |
| title_short | Genetic determinants of serum testosterone concentrations in men. |
| title_sort | genetic determinants of serum testosterone concentrations in men |
| url | https://journals.plos.org/plosgenetics/article/file?id=10.1371/journal.pgen.1002313&type=printable |
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