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dc.contributor.authorOhlsson, Claes
dc.contributor.authorWallaschofski, Henri
dc.contributor.authorLunetta, Kathryn L.
dc.contributor.authorStolk, Lisette
dc.contributor.authorPerry, John R. B.
dc.contributor.authorKoster, Annemarie
dc.contributor.authorPetersen, Ann-Kristin
dc.contributor.authorEriksson, Joel
dc.contributor.authorLehtimäki, Terho
dc.contributor.authorHuhtaniemi, Ilpo T.
dc.contributor.authorHammond, Geoffrey L.
dc.contributor.authorMaggio, Marcello
dc.contributor.authorCoviello, Andrea D.
dc.contributor.authorFerrucci, Luigi
dc.contributor.authorHeier, Margit
dc.contributor.authorHofman, Albert
dc.contributor.authorHolliday, Kate L.
dc.contributor.authorJansson, John-Olov
dc.contributor.authorKähönen, Mika
dc.contributor.authorKarasik, David
dc.contributor.authorKarlsson, Magnus K.
dc.contributor.authorKiel, Douglas P.
dc.contributor.authorLiu, Yongmei
dc.contributor.authorLjunggren, Östen
dc.contributor.authorLorentzon, Mattias
dc.contributor.authorLyytikäinen, Leo-Pekka
dc.contributor.authorMeitinger, Thomas
dc.contributor.authorMellström, Dan
dc.contributor.authorMelzer, David
dc.contributor.authorMiljkovic, Iva
dc.contributor.authorNauck, Matthias
dc.contributor.authorNilsson, Maria
dc.contributor.authorPenninx, Brenda
dc.contributor.authorPye, Stephen R.
dc.contributor.authorVasan, Ramachandran S.
dc.contributor.authorReincke, Martin
dc.contributor.authorRivadeneira, Fernando
dc.contributor.authorTajar, Abdelouahid
dc.contributor.authorTeumer, Alexander
dc.contributor.authorUitterlinden, André G.
dc.contributor.authorUlloor, Jagadish
dc.contributor.authorViikari, Jorma
dc.contributor.authorVölker, Uwe
dc.contributor.authorVölzke, Henry
dc.contributor.authorWichmann, H. Erich
dc.contributor.authorWu, Tsung-Sheng
dc.contributor.authorZhuang, Wei Vivian
dc.contributor.authorZiv, Elad
dc.contributor.authorWu, Frederick C. W.
dc.contributor.authorRaitakari, Olli
dc.contributor.authorEriksson, Anna
dc.contributor.authorBidlingmaier, Martin
dc.contributor.authorHarris, Tamara B.
dc.contributor.authorMurray, Anna
dc.contributor.authorde Jong, Frank H.
dc.contributor.authorMurabito, Joanne M.
dc.contributor.authorBhasin, Shalender
dc.contributor.authorVandenput, Liesbeth
dc.contributor.authorHaring, Robin
dc.contributor.authorAbecasis, Gonçalo R.
dc.date.accessioned2019-09-30T11:56:27Z
dc.date.issued2011
dc.identifier.citationOhlsson, Claes, Henri Wallaschofski, Kathryn L. Lunetta, Lisette Stolk, John R. B. Perry, Annemarie Koster, Ann-Kristin Petersen, et al. 2011. “Genetic Determinants of Serum Testosterone Concentrations in Men.” Edited by Gonçalo R. Abecasis. PLoS Genetics 7 (10): e1002313. https://doi.org/10.1371/journal.pgen.1002313.
dc.identifier.issn1553-7390
dc.identifier.issn1553-7404
dc.identifier.urihttp://nrs.harvard.edu/urn-3:HUL.InstRepos:41426809*
dc.description.abstractTestosterone 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 = 1.2x10(-41) and rs6258, p = 2.3x10(-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 = 5.6610216). 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.
dc.language.isoen_US
dc.publisherPublic Library of Science
dash.licenseLAA
dc.titleGenetic Determinants of Serum Testosterone Concentrations in Men
dc.typeJournal Article
dc.description.versionVersion of Record
dc.relation.journalPLoS Genetics
dash.depositing.authorHofman, Albert::23effeffdfa95fe55437cc4d561aa487::600
dc.date.available2019-09-30T11:56:27Z
dash.workflow.comments1Science Serial ID 83999
dc.identifier.doi10.1371/journal.pgen.1002313
dash.source.volume7;10


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