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Genetic determinants of serum testosterone concentrations in men. 2011
Claes Ohlsson, and
Henri Wallaschofski, and
Kathryn L Lunetta, and
Lisette Stolk, and
John R B Perry, and
Annemarie Koster, and
Ann-Kristin Petersen, and
Joel Eriksson, and
Terho Lehtimäki, and
Ilpo T Huhtaniemi, and
Geoffrey L Hammond, and
Marcello Maggio, and
Andrea D Coviello, and
, and
Luigi Ferrucci, and
Margit Heier, and
Albert Hofman, and
Kate L Holliday, and
John-Olov Jansson, and
Mika Kähönen, and
David Karasik, and
Magnus K Karlsson, and
Douglas P Kiel, and
Yongmei Liu, and
Osten Ljunggren, and
Mattias Lorentzon, and
Leo-Pekka Lyytikäinen, and
Thomas Meitinger, and
Dan Mellström, and
David Melzer, and
Iva Miljkovic, and
Matthias Nauck, and
Maria Nilsson, and
Brenda Penninx, and
Stephen R Pye, and
Ramachandran S Vasan, and
Martin Reincke, and
Fernando Rivadeneira, and
Abdelouahid Tajar, and
Alexander Teumer, and
André G Uitterlinden, and
Jagadish Ulloor, and
Jorma Viikari, and
Uwe Völker, and
Henry Völzke, and
H Erich Wichmann, and
Tsung-Sheng Wu, and
Wei Vivian Zhuang, and
Elad Ziv, and
Frederick C W Wu, and
Olli Raitakari, and
Anna Eriksson, and
Martin Bidlingmaier, and
Tamara B Harris, and
Anna Murray, and
Frank H de Jong, and
Joanne M Murabito, and
Shalender Bhasin, and
Liesbeth Vandenput, and
Robin Haring
Center for Bone and Arthritis Research, Department of Internal Medicine, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Sweden. claes.ohlsson@medic.gu.se
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.
Related Publications
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Henri Wallaschofski, and
Kathryn L Lunetta, and
Lisette Stolk, and
John R B Perry, and
Annemarie Koster, and
Ann-Kristin Petersen, and
Joel Eriksson, and
Terho Lehtimäki, and
Ilpo T Huhtaniemi, and
Geoffrey L Hammond, and
Marcello Maggio, and
Andrea D Coviello, and
, and
Luigi Ferrucci, and
Margit Heier, and
Albert Hofman, and
Kate L Holliday, and
John-Olov Jansson, and
Mika Kähönen, and
David Karasik, and
Magnus K Karlsson, and
Douglas P Kiel, and
Yongmei Liu, and
Osten Ljunggren, and
Mattias Lorentzon, and
Leo-Pekka Lyytikäinen, and
Thomas Meitinger, and
Dan Mellström, and
David Melzer, and
Iva Miljkovic, and
Matthias Nauck, and
Maria Nilsson, and
Brenda Penninx, and
Stephen R Pye, and
Ramachandran S Vasan, and
Martin Reincke, and
Fernando Rivadeneira, and
Abdelouahid Tajar, and
Alexander Teumer, and
André G Uitterlinden, and
Jagadish Ulloor, and
Jorma Viikari, and
Uwe Völker, and
Henry Völzke, and
H Erich Wichmann, and
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Elad Ziv, and
Frederick C W Wu, and
Olli Raitakari, and
Anna Eriksson, and
Martin Bidlingmaier, and
Tamara B Harris, and
Anna Murray, and
Frank H de Jong, and
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Claes Ohlsson, and
Henri Wallaschofski, and
Kathryn L Lunetta, and
Lisette Stolk, and
John R B Perry, and
Annemarie Koster, and
Ann-Kristin Petersen, and
Joel Eriksson, and
Terho Lehtimäki, and
Ilpo T Huhtaniemi, and
Geoffrey L Hammond, and
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Andrea D Coviello, and
, and
Luigi Ferrucci, and
Margit Heier, and
Albert Hofman, and
Kate L Holliday, and
John-Olov Jansson, and
Mika Kähönen, and
David Karasik, and
Magnus K Karlsson, and
Douglas P Kiel, and
Yongmei Liu, and
Osten Ljunggren, and
Mattias Lorentzon, and
Leo-Pekka Lyytikäinen, and
Thomas Meitinger, and
Dan Mellström, and
David Melzer, and
Iva Miljkovic, and
Matthias Nauck, and
Maria Nilsson, and
Brenda Penninx, and
Stephen R Pye, and
Ramachandran S Vasan, and
Martin Reincke, and
Fernando Rivadeneira, and
Abdelouahid Tajar, and
Alexander Teumer, and
André G Uitterlinden, and
Jagadish Ulloor, and
Jorma Viikari, and
Uwe Völker, and
Henry Völzke, and
H Erich Wichmann, and
Tsung-Sheng Wu, and
Wei Vivian Zhuang, and
Elad Ziv, and
Frederick C W Wu, and
Olli Raitakari, and
Anna Eriksson, and
Martin Bidlingmaier, and
Tamara B Harris, and
Anna Murray, and
Frank H de Jong, and
Joanne M Murabito, and
Shalender Bhasin, and
Liesbeth Vandenput, and
Robin Haring
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Metabolism: clinical and experimental,
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Henri Wallaschofski, and
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Lisette Stolk, and
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Annemarie Koster, and
Ann-Kristin Petersen, and
Joel Eriksson, and
Terho Lehtimäki, and
Ilpo T Huhtaniemi, and
Geoffrey L Hammond, and
Marcello Maggio, and
Andrea D Coviello, and
, and
Luigi Ferrucci, and
Margit Heier, and
Albert Hofman, and
Kate L Holliday, and
John-Olov Jansson, and
Mika Kähönen, and
David Karasik, and
Magnus K Karlsson, and
Douglas P Kiel, and
Yongmei Liu, and
Osten Ljunggren, and
Mattias Lorentzon, and
Leo-Pekka Lyytikäinen, and
Thomas Meitinger, and
Dan Mellström, and
David Melzer, and
Iva Miljkovic, and
Matthias Nauck, and
Maria Nilsson, and
Brenda Penninx, and
Stephen R Pye, and
Ramachandran S Vasan, and
Martin Reincke, and
Fernando Rivadeneira, and
Abdelouahid Tajar, and
Alexander Teumer, and
André G Uitterlinden, and
Jagadish Ulloor, and
Jorma Viikari, and
Uwe Völker, and
Henry Völzke, and
H Erich Wichmann, and
Tsung-Sheng Wu, and
Wei Vivian Zhuang, and
Elad Ziv, and
Frederick C W Wu, and
Olli Raitakari, and
Anna Eriksson, and
Martin Bidlingmaier, and
Tamara B Harris, and
Anna Murray, and
Frank H de Jong, and
Joanne M Murabito, and
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Liesbeth Vandenput, and
Robin Haring
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Henri Wallaschofski, and
Kathryn L Lunetta, and
Lisette Stolk, and
John R B Perry, and
Annemarie Koster, and
Ann-Kristin Petersen, and
Joel Eriksson, and
Terho Lehtimäki, and
Ilpo T Huhtaniemi, and
Geoffrey L Hammond, and
Marcello Maggio, and
Andrea D Coviello, and
, and
Luigi Ferrucci, and
Margit Heier, and
Albert Hofman, and
Kate L Holliday, and
John-Olov Jansson, and
Mika Kähönen, and
David Karasik, and
Magnus K Karlsson, and
Douglas P Kiel, and
Yongmei Liu, and
Osten Ljunggren, and
Mattias Lorentzon, and
Leo-Pekka Lyytikäinen, and
Thomas Meitinger, and
Dan Mellström, and
David Melzer, and
Iva Miljkovic, and
Matthias Nauck, and
Maria Nilsson, and
Brenda Penninx, and
Stephen R Pye, and
Ramachandran S Vasan, and
Martin Reincke, and
Fernando Rivadeneira, and
Abdelouahid Tajar, and
Alexander Teumer, and
André G Uitterlinden, and
Jagadish Ulloor, and
Jorma Viikari, and
Uwe Völker, and
Henry Völzke, and
H Erich Wichmann, and
Tsung-Sheng Wu, and
Wei Vivian Zhuang, and
Elad Ziv, and
Frederick C W Wu, and
Olli Raitakari, and
Anna Eriksson, and
Martin Bidlingmaier, and
Tamara B Harris, and
Anna Murray, and
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Shalender Bhasin, and
Liesbeth Vandenput, and
Robin Haring
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, and
Luigi Ferrucci, and
Margit Heier, and
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Mika Kähönen, and
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Osten Ljunggren, and
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Leo-Pekka Lyytikäinen, and
Thomas Meitinger, and
Dan Mellström, and
David Melzer, and
Iva Miljkovic, and
Matthias Nauck, and
Maria Nilsson, and
Brenda Penninx, and
Stephen R Pye, and
Ramachandran S Vasan, and
Martin Reincke, and
Fernando Rivadeneira, and
Abdelouahid Tajar, and
Alexander Teumer, and
André G Uitterlinden, and
Jagadish Ulloor, and
Jorma Viikari, and
Uwe Völker, and
Henry Völzke, and
H Erich Wichmann, and
Tsung-Sheng Wu, and
Wei Vivian Zhuang, and
Elad Ziv, and
Frederick C W Wu, and
Olli Raitakari, and
Anna Eriksson, and
Martin Bidlingmaier, and
Tamara B Harris, and
Anna Murray, and
Frank H de Jong, and
Joanne M Murabito, and
Shalender Bhasin, and
Liesbeth Vandenput, and
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The aging male : the official journal of the International Society for the Study of the Aging Male,
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Annemarie Koster, and
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Joel Eriksson, and
Terho Lehtimäki, and
Ilpo T Huhtaniemi, and
Geoffrey L Hammond, and
Marcello Maggio, and
Andrea D Coviello, and
, and
Luigi Ferrucci, and
Margit Heier, and
Albert Hofman, and
Kate L Holliday, and
John-Olov Jansson, and
Mika Kähönen, and
David Karasik, and
Magnus K Karlsson, and
Douglas P Kiel, and
Yongmei Liu, and
Osten Ljunggren, and
Mattias Lorentzon, and
Leo-Pekka Lyytikäinen, and
Thomas Meitinger, and
Dan Mellström, and
David Melzer, and
Iva Miljkovic, and
Matthias Nauck, and
Maria Nilsson, and
Brenda Penninx, and
Stephen R Pye, and
Ramachandran S Vasan, and
Martin Reincke, and
Fernando Rivadeneira, and
Abdelouahid Tajar, and
Alexander Teumer, and
André G Uitterlinden, and
Jagadish Ulloor, and
Jorma Viikari, and
Uwe Völker, and
Henry Völzke, and
H Erich Wichmann, and
Tsung-Sheng Wu, and
Wei Vivian Zhuang, and
Elad Ziv, and
Frederick C W Wu, and
Olli Raitakari, and
Anna Eriksson, and
Martin Bidlingmaier, and
Tamara B Harris, and
Anna Murray, and
Frank H de Jong, and
Joanne M Murabito, and
Shalender Bhasin, and
Liesbeth Vandenput, and
Robin Haring
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Henri Wallaschofski, and
Kathryn L Lunetta, and
Lisette Stolk, and
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Annemarie Koster, and
Ann-Kristin Petersen, and
Joel Eriksson, and
Terho Lehtimäki, and
Ilpo T Huhtaniemi, and
Geoffrey L Hammond, and
Marcello Maggio, and
Andrea D Coviello, and
, and
Luigi Ferrucci, and
Margit Heier, and
Albert Hofman, and
Kate L Holliday, and
John-Olov Jansson, and
Mika Kähönen, and
David Karasik, and
Magnus K Karlsson, and
Douglas P Kiel, and
Yongmei Liu, and
Osten Ljunggren, and
Mattias Lorentzon, and
Leo-Pekka Lyytikäinen, and
Thomas Meitinger, and
Dan Mellström, and
David Melzer, and
Iva Miljkovic, and
Matthias Nauck, and
Maria Nilsson, and
Brenda Penninx, and
Stephen R Pye, and
Ramachandran S Vasan, and
Martin Reincke, and
Fernando Rivadeneira, and
Abdelouahid Tajar, and
Alexander Teumer, and
André G Uitterlinden, and
Jagadish Ulloor, and
Jorma Viikari, and
Uwe Völker, and
Henry Völzke, and
H Erich Wichmann, and
Tsung-Sheng Wu, and
Wei Vivian Zhuang, and
Elad Ziv, and
Frederick C W Wu, and
Olli Raitakari, and
Anna Eriksson, and
Martin Bidlingmaier, and
Tamara B Harris, and
Anna Murray, and
Frank H de Jong, and
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Shalender Bhasin, and
Liesbeth Vandenput, and
Robin Haring
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Henri Wallaschofski, and
Kathryn L Lunetta, and
Lisette Stolk, and
John R B Perry, and
Annemarie Koster, and
Ann-Kristin Petersen, and
Joel Eriksson, and
Terho Lehtimäki, and
Ilpo T Huhtaniemi, and
Geoffrey L Hammond, and
Marcello Maggio, and
Andrea D Coviello, and
, and
Luigi Ferrucci, and
Margit Heier, and
Albert Hofman, and
Kate L Holliday, and
John-Olov Jansson, and
Mika Kähönen, and
David Karasik, and
Magnus K Karlsson, and
Douglas P Kiel, and
Yongmei Liu, and
Osten Ljunggren, and
Mattias Lorentzon, and
Leo-Pekka Lyytikäinen, and
Thomas Meitinger, and
Dan Mellström, and
David Melzer, and
Iva Miljkovic, and
Matthias Nauck, and
Maria Nilsson, and
Brenda Penninx, and
Stephen R Pye, and
Ramachandran S Vasan, and
Martin Reincke, and
Fernando Rivadeneira, and
Abdelouahid Tajar, and
Alexander Teumer, and
André G Uitterlinden, and
Jagadish Ulloor, and
Jorma Viikari, and
Uwe Völker, and
Henry Völzke, and
H Erich Wichmann, and
Tsung-Sheng Wu, and
Wei Vivian Zhuang, and
Elad Ziv, and
Frederick C W Wu, and
Olli Raitakari, and
Anna Eriksson, and
Martin Bidlingmaier, and
Tamara B Harris, and
Anna Murray, and
Frank H de Jong, and
Joanne M Murabito, and
Shalender Bhasin, and
Liesbeth Vandenput, and
Robin Haring
January 1993,
International journal of fertility,
Claes Ohlsson, and
Henri Wallaschofski, and
Kathryn L Lunetta, and
Lisette Stolk, and
John R B Perry, and
Annemarie Koster, and
Ann-Kristin Petersen, and
Joel Eriksson, and
Terho Lehtimäki, and
Ilpo T Huhtaniemi, and
Geoffrey L Hammond, and
Marcello Maggio, and
Andrea D Coviello, and
, and
Luigi Ferrucci, and
Margit Heier, and
Albert Hofman, and
Kate L Holliday, and
John-Olov Jansson, and
Mika Kähönen, and
David Karasik, and
Magnus K Karlsson, and
Douglas P Kiel, and
Yongmei Liu, and
Osten Ljunggren, and
Mattias Lorentzon, and
Leo-Pekka Lyytikäinen, and
Thomas Meitinger, and
Dan Mellström, and
David Melzer, and
Iva Miljkovic, and
Matthias Nauck, and
Maria Nilsson, and
Brenda Penninx, and
Stephen R Pye, and
Ramachandran S Vasan, and
Martin Reincke, and
Fernando Rivadeneira, and
Abdelouahid Tajar, and
Alexander Teumer, and
André G Uitterlinden, and
Jagadish Ulloor, and
Jorma Viikari, and
Uwe Völker, and
Henry Völzke, and
H Erich Wichmann, and
Tsung-Sheng Wu, and
Wei Vivian Zhuang, and
Elad Ziv, and
Frederick C W Wu, and
Olli Raitakari, and
Anna Eriksson, and
Martin Bidlingmaier, and
Tamara B Harris, and
Anna Murray, and
Frank H de Jong, and
Joanne M Murabito, and
Shalender Bhasin, and
Liesbeth Vandenput, and
Robin Haring
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International journal of cancer,
Claes Ohlsson, and
Henri Wallaschofski, and
Kathryn L Lunetta, and
Lisette Stolk, and
John R B Perry, and
Annemarie Koster, and
Ann-Kristin Petersen, and
Joel Eriksson, and
Terho Lehtimäki, and
Ilpo T Huhtaniemi, and
Geoffrey L Hammond, and
Marcello Maggio, and
Andrea D Coviello, and
, and
Luigi Ferrucci, and
Margit Heier, and
Albert Hofman, and
Kate L Holliday, and
John-Olov Jansson, and
Mika Kähönen, and
David Karasik, and
Magnus K Karlsson, and
Douglas P Kiel, and
Yongmei Liu, and
Osten Ljunggren, and
Mattias Lorentzon, and
Leo-Pekka Lyytikäinen, and
Thomas Meitinger, and
Dan Mellström, and
David Melzer, and
Iva Miljkovic, and
Matthias Nauck, and
Maria Nilsson, and
Brenda Penninx, and
Stephen R Pye, and
Ramachandran S Vasan, and
Martin Reincke, and
Fernando Rivadeneira, and
Abdelouahid Tajar, and
Alexander Teumer, and
André G Uitterlinden, and
Jagadish Ulloor, and
Jorma Viikari, and
Uwe Völker, and
Henry Völzke, and
H Erich Wichmann, and
Tsung-Sheng Wu, and
Wei Vivian Zhuang, and
Elad Ziv, and
Frederick C W Wu, and
Olli Raitakari, and
Anna Eriksson, and
Martin Bidlingmaier, and
Tamara B Harris, and
Anna Murray, and
Frank H de Jong, and
Joanne M Murabito, and
Shalender Bhasin, and
Liesbeth Vandenput, and
Robin Haring
January 2019,
Frontiers in pharmacology,
