作者
Richard J. Fantus,Rong Na,Jun S. Wei,Zhuqing Shi,Kyle Resurreccion,Joshua A. Halpern,Omar E. Franco,Simon W. Hayward,William Isaacs,Lilly S. Zheng,Jianfeng Xu,B.R. Helfand
摘要
You have accessJournal of UrologySexual Function/Dysfunction: Evaluation II (PD30)1 Sep 2021PD30-10 THE GENETIC BASIS OF LOW TESTOSTERONE AND ITS CLINICAL UTILITY: RESULTS OF THE UK BIOBANK Richard Fantus, Rong Na, Jun Wei, Zhuqing Shi, Kyle Resurreccion, Joshua Halpern, Omar Franco, Simon Hayward, William Isaacs, Lilly Zheng, Jianfeng Xu, and Brian Helfand Richard FantusRichard Fantus More articles by this author , Rong NaRong Na More articles by this author , Jun WeiJun Wei More articles by this author , Zhuqing ShiZhuqing Shi More articles by this author , Kyle ResurreccionKyle Resurreccion More articles by this author , Joshua HalpernJoshua Halpern More articles by this author , Omar FrancoOmar Franco More articles by this author , Simon HaywardSimon Hayward More articles by this author , William IsaacsWilliam Isaacs More articles by this author , Lilly ZhengLilly Zheng More articles by this author , Jianfeng XuJianfeng Xu More articles by this author , and Brian HelfandBrian Helfand More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000002031.10AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Despite overwhelming evidence of genetic contributions to testosterone levels, there has been a paucity of studies focused on the heritability of low testosterone (LowT). We sought to determine the heritability of the LowT and create a clinical tool to that could be used to identify susceptible men through a large-scale, multi-stage genome wide association study (GWAS). METHODS: Using the United Kingdom Biobank (UKB), a database containing 500,000 participants with genetic data and health care information, we conducted a multi-stage age controlled GWAS. We included all Caucasian men without prostate cancer and without testicular, hypothalamic, pituitary and adrenal disorders. Low testosterone was defined as <8nmol/L. Single nucleotide polymorphisms (SNPs) that were identified in the initial cohort and confirmed in the validation cohort were used to create a genetic risk score (GRS) for LowT. RESULTS: Of the 186,062 men that met inclusion criterion 11.9% had LowT. Men with LowT were significantly older (57.7 years) and had an elevated body mass index (BMI, 30.4), compared to men with normal testosterone (56.5 years, 27.52 respectively, both P<0.0001). We identified 141 loci associated with the LowT phenotype, which accounts for nearly 20% of the heritability of LowT. To determine the combined effect of each loci we created a GRS based on 42 SNPs that were independently associated with LowT. GRS demonstrated that men in the bottom decile had a 4.98-fold lower risk of having LowT compared to men in the top decile (P<0.01, Figure). CONCLUSIONS: This large scale GWAS identified SNPs related to the phenotype of LowT. Using identified SNPs our novel GRS can help predict men at risk for LowT which ultimately may focus screening efforts on men most likely to experience. Source of Funding: None © 2021 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 206Issue Supplement 3September 2021Page: e536-e536 Advertisement Copyright & Permissions© 2021 by American Urological Association Education and Research, Inc.MetricsAuthor Information Richard Fantus More articles by this author Rong Na More articles by this author Jun Wei More articles by this author Zhuqing Shi More articles by this author Kyle Resurreccion More articles by this author Joshua Halpern More articles by this author Omar Franco More articles by this author Simon Hayward More articles by this author William Isaacs More articles by this author Lilly Zheng More articles by this author Jianfeng Xu More articles by this author Brian Helfand More articles by this author Expand All Advertisement Loading ...