Genetic determinants of serum testosterone concentrations in men.

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Ohlsson, Claes,1965Gothenburg University,Göteborgs universitet,Centre for Bone and Arthritis Research,Institutionen för medicin, avdelningen för invärtesmedicin,Institute of Medicine, Department of Internal Medicine (author)

Genetic determinants of serum testosterone concentrations in men.

Article/chapterEnglish2011

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2011-10-06
Public Library of Science (PLoS),2011

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LIBRIS-ID:oai:gup.ub.gu.se/152144
https://gup.ub.gu.se/publication/152144URI
https://doi.org/10.1371/journal.pgen.1002313DOI
https://lup.lub.lu.se/record/2253051URI
https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-162707URI

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Language:English

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SwePubSwePub

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Subject category:ref swepub-contenttype
Subject category:art swepub-publicationtype

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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.

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Wallaschofski, Henri (author)
Lunetta, Kathryn L (author)
Stolk, Lisette (author)
Perry, John R B (author)
Koster, Annemarie (author)
Petersen, Ann-Kristin (author)
Eriksson, JoelGothenburg University,Göteborgs universitet,Centre for Bone and Arthritis Research(Swepub:gu)xerjoe (author)
Lehtimäki, Terho (author)
Huhtaniemi, Ilpo T (author)
Hammond, Geoffrey L (author)
Maggio, Marcello (author)
Coviello, Andrea D (author)
Ferrucci, Luigi (author)
Heier, Margit (author)
Hofman, Albert (author)
Holliday, Kate L (author)
Jansson, John-Olov,1954Gothenburg University,Göteborgs universitet,Institutionen för neurovetenskap och fysiologi, sektionen för fysiologi,Institute of Neuroscience and Physiology, Department of Physiology(Swepub:gu)xjanjo (author)
Kähönen, Mika (author)
Karasik, David (author)
Karlsson, MagnusLund University,Lunds universitet,Ortopedi - klinisk och molekylär osteoporosforskning,Forskargrupper vid Lunds universitet,Orthopedics - Clinical and Molecular Osteoporosis Research,Lund University Research Groups(Swepub:lu)orto-mka (author)
Kiel, Douglas P (author)
Liu, Yongmei (author)
Ljunggren, ÖstenUppsala universitet,Institutionen för medicinska vetenskaper(Swepub:uu)osteljun (author)
Lorentzon, Mattias,1970Gothenburg University,Göteborgs universitet,Centre for Bone and Arthritis Research,Institutionen för medicin, avdelningen för invärtesmedicin,Institute of Medicine, Department of Internal Medicine(Swepub:gu)xlomat (author)
Lyytikäinen, Leo-Pekka (author)
Meitinger, Thomas (author)
Mellström, Dan,1945 (author)
Melzer, David (author)
Miljkovic, Iva (author)
Nauck, Matthias (author)
Nilsson, MariaGothenburg University,Göteborgs universitet,Centre for Bone and Arthritis Research (author)
Penninx, Brenda (author)
Pye, Stephen R (author)
Vasan, Ramachandran S (author)
Reincke, Martin (author)
Rivadeneira, Fernando (author)
Tajar, Abdelouahid (author)
Teumer, Alexander (author)
Uitterlinden, André G (author)
Ulloor, Jagadish (author)
Viikari, Jorma (author)
Völker, Uwe (author)
Völzke, Henry (author)
Wichmann, H Erich (author)
Wu, Tsung-Sheng (author)
Zhuang, Wei Vivian (author)
Ziv, Elad (author)
Wu, Frederick C W (author)
Raitakari, Olli (author)
Eriksson, Anna-Lena,1971Gothenburg University,Göteborgs universitet,Institutionen för medicin, avdelningen för klinisk prövning och entreprenörskap,Institutionen för medicin, avdelningen för invärtesmedicin,Centre for Bone and Arthritis Research,Institute of Medicine, Department of Clinical Trials and Entrepreneurship,Institute of Medicine, Department of Internal Medicine(Swepub:gu)xeannj (author)
Bidlingmaier, Martin (author)
Harris, Tamara B (author)
Murray, Anna (author)
de Jong, Frank H (author)
Murabito, Joanne M (author)
Bhasin, Shalender (author)
Vandenput, Liesbeth,1974Gothenburg University,Göteborgs universitet,Centre for Bone and Arthritis Research,Institutionen för medicin, avdelningen för invärtesmedicin,Institute of Medicine, Department of Internal Medicine(Swepub:gu)xvanli (author)
Haring, Robin (author)
Göteborgs universitetCentre for Bone and Arthritis Research (creator_code:org_t)

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In:PLoS genetics: Public Library of Science (PLoS)7:101553-74041553-7390

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By the author/editor: Ohlsson, Claes, ...; Wallaschofski, H ...; Lunetta, Kathryn ...; Stolk, Lisette; Perry, John R B; Koster, Annemari ...; show more...; Petersen, Ann-Kr ...; Eriksson, Joel; Lehtimäki, Terho; Huhtaniemi, Ilpo ...; Hammond, Geoffre ...; Maggio, Marcello; Coviello, Andrea ...; Ferrucci, Luigi; Heier, Margit; Hofman, Albert; Holliday, Kate L; Jansson, John-Ol ...; Kähönen, Mika; Karasik, David; Karlsson, Magnus; Kiel, Douglas P; Liu, Yongmei; Ljunggren, Östen; Lorentzon, Matti ...; Lyytikäinen, Leo ...; Meitinger, Thoma ...; Mellström, Dan, ...; Melzer, David; Miljkovic, Iva; Nauck, Matthias; Nilsson, Maria; Penninx, Brenda; Pye, Stephen R; Vasan, Ramachand ...; Reincke, Martin; Rivadeneira, Fer ...; Tajar, Abdelouah ...; Teumer, Alexande ...; Uitterlinden, An ...; Ulloor, Jagadish; Viikari, Jorma; Völker, Uwe; Völzke, Henry; Wichmann, H Eric ...; Wu, Tsung-Sheng; Zhuang, Wei Vivi ...; Ziv, Elad; Wu, Frederick C ...; Raitakari, Olli; Eriksson, Anna-L ...; Bidlingmaier, Ma ...; Harris, Tamara B; Murray, Anna; de Jong, Frank H; Murabito, Joanne ...; Bhasin, Shalende ...; Vandenput, Liesb ...; Haring, Robin; show less...

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