Genetic determinants of serum testosterone concentrations in men

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, Study Group Emas Study Group, Luigi Ferrucci, Margit Heier, Albert Hofman, Kate L. Holliday, John Olov Jansson, Mika Kähönen & 40 others David Karasik, Magnus K. Karlsson, Douglas P. Kiel, Yongmei Liu, Östen 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

Research output: Contribution to journalArticle

102 Citations (Scopus)

Abstract

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 -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

Original languageEnglish
Article numbere1002313
JournalPLoS Genetics
Volume7
Issue number10
DOIs
StatePublished - Oct 2011
Externally publishedYes

Fingerprint

testosterone
Testosterone
serum
Serum
allele
polymorphism
genome
Alleles
genetic polymorphism
Genome
alleles
loci
Genetic Loci
obesity
osteoporosis
meta-analysis
X Chromosome
X chromosome
morbidity
heritability

All Science Journal Classification (ASJC) codes

  • Genetics
  • Molecular Biology
  • Ecology, Evolution, Behavior and Systematics
  • Cancer Research
  • Genetics(clinical)

Cite this

Ohlsson, C., Wallaschofski, H., Lunetta, K. L., Stolk, L., Perry, J. R. B., Koster, A., ... Haring, R. (2011). Genetic determinants of serum testosterone concentrations in men. PLoS Genetics, 7(10), [e1002313]. https://doi.org/10.1371/journal.pgen.1002313

Genetic determinants of serum testosterone concentrations in men. / Ohlsson, Claes; Wallaschofski, Henri; Lunetta, Kathryn L.; Stolk, Lisette; Perry, John R B; Koster, Annemarie; Petersen, Ann Kristin; Eriksson, Joel; Lehtimäki, Terho; Huhtaniemi, Ilpo T.; Hammond, Geoffrey L.; Maggio, Marcello; Coviello, Andrea D.; Emas Study Group, Study Group; Ferrucci, Luigi; Heier, Margit; Hofman, Albert; Holliday, Kate L.; Jansson, John Olov; Kähönen, Mika; Karasik, David; Karlsson, Magnus K.; Kiel, Douglas P.; Liu, Yongmei; Ljunggren, Östen; Lorentzon, Mattias; Lyytikäinen, Leo Pekka; Meitinger, Thomas; Mellström, Dan; Melzer, David; Miljkovic, Iva; Nauck, Matthias; Nilsson, Maria; Penninx, Brenda; Pye, Stephen R.; Vasan, Ramachandran S.; Reincke, Martin; Rivadeneira, Fernando; Tajar, Abdelouahid; Teumer, Alexander; Uitterlinden, André G.; Ulloor, Jagadish; Viikari, Jorma; Völker, Uwe; Völzke, Henry; Wichmann, H. Erich; Wu, Tsung Sheng; Zhuang, Wei Vivian; Ziv, Elad; Wu, Frederick C W; Raitakari, Olli; Eriksson, Anna; Bidlingmaier, Martin; Harris, Tamara B.; Murray, Anna; de Jong, Frank H.; Murabito, Joanne M.; Bhasin, Shalender; Vandenput, Liesbeth; Haring, Robin.

In: PLoS Genetics, Vol. 7, No. 10, e1002313, 10.2011.

Research output: Contribution to journalArticle

Ohlsson, C, Wallaschofski, H, Lunetta, KL, Stolk, L, Perry, JRB, Koster, A, Petersen, AK, Eriksson, J, Lehtimäki, T, Huhtaniemi, IT, Hammond, GL, Maggio, M, Coviello, AD, Emas Study Group, SG, Ferrucci, L, Heier, M, Hofman, A, Holliday, KL, Jansson, JO, Kähönen, M, Karasik, D, Karlsson, MK, Kiel, DP, Liu, Y, Ljunggren, Ö, Lorentzon, M, Lyytikäinen, LP, Meitinger, T, Mellström, D, Melzer, D, Miljkovic, I, Nauck, M, Nilsson, M, Penninx, B, Pye, SR, Vasan, RS, Reincke, M, Rivadeneira, F, Tajar, A, Teumer, A, Uitterlinden, AG, Ulloor, J, Viikari, J, Völker, U, Völzke, H, Wichmann, HE, Wu, TS, Zhuang, WV, Ziv, E, Wu, FCW, Raitakari, O, Eriksson, A, Bidlingmaier, M, Harris, TB, Murray, A, de Jong, FH, Murabito, JM, Bhasin, S, Vandenput, L & Haring, R 2011, 'Genetic determinants of serum testosterone concentrations in men', PLoS Genetics, vol. 7, no. 10, e1002313. https://doi.org/10.1371/journal.pgen.1002313
Ohlsson C, Wallaschofski H, Lunetta KL, Stolk L, Perry JRB, Koster A et al. Genetic determinants of serum testosterone concentrations in men. PLoS Genetics. 2011 Oct;7(10). e1002313. https://doi.org/10.1371/journal.pgen.1002313
Ohlsson, Claes ; Wallaschofski, Henri ; Lunetta, Kathryn L. ; Stolk, Lisette ; Perry, John R B ; Koster, Annemarie ; Petersen, Ann Kristin ; Eriksson, Joel ; Lehtimäki, Terho ; Huhtaniemi, Ilpo T. ; Hammond, Geoffrey L. ; Maggio, Marcello ; Coviello, Andrea D. ; Emas Study Group, Study Group ; Ferrucci, Luigi ; Heier, Margit ; Hofman, Albert ; Holliday, Kate L. ; Jansson, John Olov ; Kähönen, Mika ; Karasik, David ; Karlsson, Magnus K. ; Kiel, Douglas P. ; Liu, Yongmei ; Ljunggren, Östen ; Lorentzon, Mattias ; Lyytikäinen, Leo Pekka ; Meitinger, Thomas ; Mellström, Dan ; Melzer, David ; Miljkovic, Iva ; Nauck, Matthias ; Nilsson, Maria ; Penninx, Brenda ; Pye, Stephen R. ; Vasan, Ramachandran S. ; Reincke, Martin ; Rivadeneira, Fernando ; Tajar, Abdelouahid ; Teumer, Alexander ; Uitterlinden, André G. ; Ulloor, Jagadish ; Viikari, Jorma ; Völker, Uwe ; Völzke, Henry ; Wichmann, H. Erich ; Wu, Tsung Sheng ; Zhuang, Wei Vivian ; Ziv, Elad ; Wu, Frederick C W ; Raitakari, Olli ; Eriksson, Anna ; Bidlingmaier, Martin ; Harris, Tamara B. ; Murray, Anna ; de Jong, Frank H. ; Murabito, Joanne M. ; Bhasin, Shalender ; Vandenput, Liesbeth ; Haring, Robin. / Genetic determinants of serum testosterone concentrations in men. In: PLoS Genetics. 2011 ; Vol. 7, No. 10.
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