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Fellowship"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2024,11,18]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Context<\/jats:title>\n                  <jats:p>Trinucleotide repeats in the androgen receptor have been proposed to influence testosterone signaling in men, but the clinical relevance of these trinucleotide repeats remains controversial.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Objective<\/jats:title>\n                  <jats:p>To examine how androgen receptor trinucleotide repeat lengths affect androgen-related traits and disease risks and whether they influence the clinical importance of circulating testosterone levels.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>We quantified CAG and GGC repeat lengths in the androgen receptor (AR) gene of European-ancestry male participants in the UK Biobank from whole-genome and whole-exome sequence data using ExpansionHunter and tested associations with androgen-related traits and diseases. We also examined whether the associations between testosterone levels and these outcomes were affected by adjustment for the repeat lengths.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>We successfully quantified the repeat lengths from whole-genome and\/or whole-exome sequence data in 181 217 males. Both repeat lengths were shown to be positively associated with circulating total testosterone level and bone mineral density, whereas CAG repeat length was negatively associated with male-pattern baldness, but their effects were relatively small and were not associated with most of the other outcomes. Circulating total testosterone level was associated with various outcomes, but this relationship was not affected by adjustment for the repeat lengths.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusion<\/jats:title>\n                  <jats:p>In this large-scale study, we found that longer CAG and GGC repeats in the AR gene influence androgen resistance, elevate circulating testosterone level via a feedback loop, and play a role in some androgen-targeted tissues. Generally, however, circulating testosterone level is a more important determinant of androgen action in males than repeat lengths.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1210\/clinem\/dgae302","type":"journal-article","created":{"date-parts":[[2024,5,3]],"date-time":"2024-05-03T17:30:30Z","timestamp":1714757430000},"page":"3234-3244","source":"Crossref","is-referenced-by-count":8,"title":["The Influence of Trinucleotide Repeats in the Androgen Receptor Gene on Androgen-related Traits and Diseases"],"prefix":"10.1210","volume":"109","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7644-309X","authenticated-orcid":false,"given":"Takayoshi","family":"Sasako","sequence":"first","affiliation":[{"name":"McGill University , Montr\u00e9al, Qu\u00e9bec H3T 1E2 ,","place":["Canada"]},{"name":"Lady Davis Institute for Medical Research, Jewish General Hospital , Montr\u00e9al, Qu\u00e9bec H3T 1E2 ,","place":["Canada"]},{"name":"Tanaka Diabetes Clinic Omiya , Saitama 330-0846 ,","place":["Japan"]},{"name":"Department of Diabetes and Metabolic Diseases, Graduate School of Medicine, The University of Tokyo , 7-3-1 Hongo, Bunkyo-Ku, Tokyo 113-0033 ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yann","family":"Ilboudo","sequence":"additional","affiliation":[{"name":"Lady Davis Institute for Medical Research, Jewish General Hospital , Montr\u00e9al, Qu\u00e9bec H3T 1E2 ,","place":["Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kevin Y H","family":"Liang","sequence":"additional","affiliation":[{"name":"Lady Davis Institute for Medical Research, Jewish General Hospital , Montr\u00e9al, Qu\u00e9bec H3T 1E2 ,","place":["Canada"]},{"name":"Quantitative Life Sciences Program, McGill University , Montr\u00e9al, Qu\u00e9bec H3T 1E2 ,","place":["Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yiheng","family":"Chen","sequence":"additional","affiliation":[{"name":"Lady Davis Institute for Medical Research, Jewish General Hospital , Montr\u00e9al, Qu\u00e9bec H3T 1E2 ,","place":["Canada"]},{"name":"Department of Human Genetics, McGill University , Montr\u00e9al, Qu\u00e9bec H3T 1E2 ,","place":["Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Satoshi","family":"Yoshiji","sequence":"additional","affiliation":[{"name":"Lady Davis Institute for Medical Research, Jewish General Hospital , Montr\u00e9al, Qu\u00e9bec H3T 1E2 ,","place":["Canada"]},{"name":"Department of Human Genetics, McGill University , Montr\u00e9al, Qu\u00e9bec H3T 1E2 ,","place":["Canada"]},{"name":"Kyoto-McGill International Collaborative Program in Genomic Medicine, Graduate School of Medicine, Kyoto University , Kyoto 606-8501 ,","place":["Japan"]},{"name":"Japan Society for the Promotion of Science , Tokyo 102-0083 ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3746-9086","authenticated-orcid":false,"given":"J Brent","family":"Richards","sequence":"additional","affiliation":[{"name":"Lady Davis Institute for Medical Research, Jewish General Hospital , Montr\u00e9al, Qu\u00e9bec H3T 1E2 ,","place":["Canada"]},{"name":"Department of Human Genetics, McGill University , Montr\u00e9al, Qu\u00e9bec H3T 1E2 ,","place":["Canada"]},{"name":"Five Prime Sciences Inc , Montr\u00e9al, Qu\u00e9bec H3Y 2W4 ,","place":["Canada"]},{"name":"10Department of Epidemiology, Biostatistics and Occupational Health, McGill University , Montr\u00e9al, Qu\u00e9bec H3T 1E2 ,","place":["Canada"]},{"name":"11Department of Twin Research, King's College London , London WC2R 2LS 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