PD30-03 GENETIC ANALYSES IDENTIFIES >150 NOVEL LOCI ASSOCIATED WITH LOW TESTOSTERONE

Abstract

You have accessJournal of UrologySexual Function/Dysfunction: Evaluation II (PD30)1 Sep 2021PD30-03 GENETIC ANALYSES IDENTIFIES >150 NOVEL LOCI ASSOCIATED WITH LOW TESTOSTERONE Richard Fantus, 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 , 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.0000000000002031.03AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Hereditary factors significantly impact a patient’s risk of developing low testosterone (LowT). Despite major advances in genotyping and sequencing technologies, there have been limited explanations for the heritability of LowT. We sought to identify heritable causes of LowT using genotyping data from a prospective, large-scale population database. METHODS: Using the United Kingdom Biobank (UKB), a dataset containing half a million peoples’ genetic and health care data, we performed a multi-stage genome wide association study (GWAS) to identify single nucleotide polymorphisms (SNPs) associated with the LowT phenotype in Caucasian men. Subsequent cis expression quantitative trait loci (eQTL) analyses were performed on each significant SNP to identify possible differences in gene transcription in androgen related tissues (testis, adrenal, pituitary, liver, prostate, and adipose). Using the Genotype-Tissue Expression (GTEx) project portal, several candidate genes were identified. RESULTS: cis-eQTL analysis of the identified 141 SNPS associated with LowT, revealed 155 genes represented by 79 neighboring loci with differential expression in men with LowT compared to men without LowT(Figure). Of the 79 loci, two have been previously implicated in testosterone metabolism (JMJD1C at 10q21.3 and SHBG at 17p13.1). In addition, we identified several candidate genes that may be responsible for the low T phenotype at the pituitary level (LCMT2 at 15q15.3, LIN28B at 6q16.3, and ZBTB4 at 17p13.1). CONCLUSIONS: This large scale GWAS and cis-eQTL has not only validated previously identified proteins potentially responsible for causing LowT but discovered over 153 new candidate genes that may influence T expression. While we report several genes with biologically plausible mechanisms for causing LowT, future studies are needed to explore the relationship between these genes and the LowT phenotype. Source of Funding: None © 2021 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 206Issue Supplement 3September 2021Page: e532-e533 Advertisement Copyright & Permissions© 2021 by American Urological Association Education and Research, Inc.MetricsAuthor Information Richard Fantus More articles by this author 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 ...