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; 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

doi:10.1371/journal.pgen.1002313

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 KähönenDavid 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

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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 language	English (US)
Article number	e1002313
Journal	PLoS Genetics
Volume	7
Issue number	10
DOIs	https://doi.org/10.1371/journal.pgen.1002313
State	Published - Oct 2011
Externally published	Yes

ASJC Scopus subject areas

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

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10.1371/journal.pgen.1002313

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Ohlsson, C., Wallaschofski, H., Lunetta, K. L., Stolk, L., Perry, J. R. B., Koster, A., Petersen, A. K., Eriksson, J., Lehtimäki, T., Huhtaniemi, I. T., Hammond, G. L., Maggio, M., Coviello, A. D., Emas Study Group, S. G., Ferrucci, L., Heier, M., Hofman, A., Holliday, K. L., Jansson, J. O., ... Haring, R. (2011). Genetic determinants of serum testosterone concentrations in men. PLoS Genetics, 7(10), Article e1002313. https://doi.org/10.1371/journal.pgen.1002313

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

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title = "Genetic determinants of serum testosterone concentrations in men",

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",

author = "Claes Ohlsson and Henri Wallaschofski and Lunetta, {Kathryn L.} and Lisette Stolk and Perry, {John R B} and Annemarie Koster and Petersen, {Ann Kristin} and Joel Eriksson and Terho Lehtim{\"a}ki and Huhtaniemi, {Ilpo T.} and Hammond, {Geoffrey L.} and Marcello Maggio and Coviello, {Andrea D.} and {Emas Study Group}, {Study Group} and Luigi Ferrucci and Margit Heier and Albert Hofman and Holliday, {Kate L.} and Jansson, {John Olov} and Mika K{\"a}h{\"o}nen and David Karasik and Karlsson, {Magnus K.} and Kiel, {Douglas P.} and Yongmei Liu and {\"O}sten Ljunggren and Mattias Lorentzon and Lyytik{\"a}inen, {Leo Pekka} and Thomas Meitinger and Dan Mellstr{\"o}m and David Melzer and Iva Miljkovic and Matthias Nauck and Maria Nilsson and Brenda Penninx and Pye, {Stephen R.} and Vasan, {Ramachandran S.} and Martin Reincke and Fernando Rivadeneira and Abdelouahid Tajar and Alexander Teumer and Uitterlinden, {Andr{\'e} G.} and Jagadish Ulloor and Jorma Viikari and Uwe V{\"o}lker and Henry V{\"o}lzke and Wichmann, {H. Erich} and Wu, {Tsung Sheng} and Zhuang, {Wei Vivian} and Elad Ziv and Wu, {Frederick C W} and Olli Raitakari and Anna Eriksson and Martin Bidlingmaier and Harris, {Tamara B.} and Anna Murray and {de Jong}, {Frank H.} and Murabito, {Joanne M.} and Shalender Bhasin and Liesbeth Vandenput and Robin Haring",

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doi = "10.1371/journal.pgen.1002313",

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AU - Ohlsson, Claes

AU - Wallaschofski, Henri

AU - Lunetta, Kathryn L.

AU - Stolk, Lisette

AU - Perry, John R B

AU - Koster, Annemarie

AU - Petersen, Ann Kristin

AU - Eriksson, Joel

AU - Lehtimäki, Terho

AU - Huhtaniemi, Ilpo T.

AU - Hammond, Geoffrey L.

AU - Maggio, Marcello

AU - Coviello, Andrea D.

AU - Emas Study Group, Study Group

AU - Ferrucci, Luigi

AU - Heier, Margit

AU - Hofman, Albert

AU - Holliday, Kate L.

AU - Jansson, John Olov

AU - Kähönen, Mika

AU - Karasik, David

AU - Karlsson, Magnus K.

AU - Kiel, Douglas P.

AU - Liu, Yongmei

AU - Ljunggren, Östen

AU - Lorentzon, Mattias

AU - Lyytikäinen, Leo Pekka

AU - Meitinger, Thomas

AU - Mellström, Dan

AU - Melzer, David

AU - Miljkovic, Iva

AU - Nauck, Matthias

AU - Nilsson, Maria

AU - Penninx, Brenda

AU - Pye, Stephen R.

AU - Vasan, Ramachandran S.

AU - Reincke, Martin

AU - Rivadeneira, Fernando

AU - Tajar, Abdelouahid

AU - Teumer, Alexander

AU - Uitterlinden, André G.

AU - Ulloor, Jagadish

AU - Viikari, Jorma

AU - Völker, Uwe

AU - Völzke, Henry

AU - Wichmann, H. Erich

AU - Wu, Tsung Sheng

AU - Zhuang, Wei Vivian

AU - Ziv, Elad

AU - Wu, Frederick C W

AU - Raitakari, Olli

AU - Eriksson, Anna

AU - Bidlingmaier, Martin

AU - Harris, Tamara B.

AU - Murray, Anna

AU - de Jong, Frank H.

AU - Murabito, Joanne M.

AU - Bhasin, Shalender

AU - Vandenput, Liesbeth

AU - Haring, Robin

PY - 2011/10

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Genetic determinants of serum testosterone concentrations in men

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