{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,10]],"date-time":"2026-07-10T17:02:47Z","timestamp":1783702967615,"version":"3.55.0"},"reference-count":55,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2025,3,27]],"date-time":"2025-03-27T00:00:00Z","timestamp":1743033600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82371635"],"award-info":[{"award-number":["82371635"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82071637"],"award-info":[{"award-number":["82071637"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100009558","name":"University Natural Science Research Project of Anhui Province","doi-asserted-by":"publisher","award":["2023AH053308"],"award-info":[{"award-number":["2023AH053308"]}],"id":[{"id":"10.13039\/501100009558","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Andrology"],"published-print":{"date-parts":[[2026,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Erectile dysfunction (ED) is a common condition affecting millions of men worldwide. While genome\u2010wide association studies (GWAS) have identified genetic loci associated with ED risk, the potential causative genes and their biological mechanisms leading to ED remain largely unexplored.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objectives<\/jats:title>\n                    <jats:p>This study aimed to conduct a comprehensive cross\u2010tissue transcriptome\u2010wide association study (TWAS) to identify susceptibility genes associated with ED risk.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Materials and methods<\/jats:title>\n                    <jats:p>We conducted a cross\u2010tissue TWAS analysis integrating GWAS data for ED with eQTL files from Genotype\u2010Tissue Expression Project (GTEx) V8. We used the unified test for molecular signatures (UTMOST) for cross\u2010tissue analysis and functional summary\u2010based imputation (FUSION) for single\u2010tissue validation. Candidate genes were further validated through multi\u2010marker analysis of genomic annotation (MAGMA), conditional and joint (COJO) analysis, and colocalization analysis.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>The cross\u2010tissue TWAS analysis identified 118 significant genes associated with ED, while the single\u2010tissue TWAS validation revealed 3804 significant genes. Nine candidate genes (CPT1B, CSF2RB, DNAH7, EHD3, L3MBTL2, LCLAT1, MDH1B, REEP1, and SLC30A6) were consistently identified across the TWAS and MAGMA analyses. COJO analysis revealed that LCLAT1 accounted for most of the signals at their respective loci. Colocalization analysis confirmed LCLAT1 as the primary candidate gene, showing strong colocalization with ED in testis, brain cortex, and heart left ventricle.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Discussion and conclusion<\/jats:title>\n                    <jats:p>This comprehensive cross\u2010tissue TWAS analysis identified LCLAT1 as a primary susceptibility gene for ED, highlighting its potential role in the mitochondrial function and lipid metabolism. The study also revealed several secondary candidate genes that may contribute to ED through pathways related to mitochondrial dynamics, neurotransmission, and cardiovascular function. These findings provide new perspectives on the genetic architecture of ED and suggest potential targets for future research and treatment.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/andr.70034","type":"journal-article","created":{"date-parts":[[2025,3,30]],"date-time":"2025-03-30T03:51:46Z","timestamp":1743306706000},"page":"159-168","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["A cross\u2010tissue transcriptome\u2010wide association study reveals novel susceptibility genes for erectile dysfunction"],"prefix":"10.1111","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2816-0175","authenticated-orcid":false,"given":"Tianle","family":"Zhu","sequence":"first","affiliation":[{"name":"Department of Urology The First Affiliated Hospital of Anhui Medical University  Hefei China"},{"name":"Anhui Province Key Laboratory of Urological and Andrological Diseases Research and Medical 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