{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,7]],"date-time":"2026-02-07T13:44:44Z","timestamp":1770471884084,"version":"3.49.0"},"reference-count":60,"publisher":"Oxford University Press (OUP)","issue":"4","license":[{"start":{"date-parts":[[2025,8,28]],"date-time":"2025-08-28T00:00:00Z","timestamp":1756339200000},"content-version":"vor","delay-in-days":58,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"name":"Young Top-notch Talent Cultivation Program of Hubei Province"},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["NSFC-82473714"],"award-info":[{"award-number":["NSFC-82473714"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,7,2]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Fat distribution patterns are increasingly linked to obesity-related cancers; however, their shared genetic determinants remain unclear. To identify shared genetic architecture between adiposity measures and obesity-related cancers. Utilizing large-scale summary statistics from genome-wide association study, we conducted genome-wide cross trait analyses of nine adiposity measures [body mass index (BMI), waist-to-hip (WTH) ratio, waist-to-hip ratio adjusted for BMI, arm fat ratio, trunk fat ratio, leg fat ratio, abdominal subcutaneous adipose tissue, gluteofemoral adipose tissue, and visceral adipose tissue] in five obesity-related cancers (colorectal cancer, esophageal adenocarcinoma, breast cancer, endometrial cancer, and ovarian cancer) to characterize their shared genetic architecture, biological pathways, and causal relationships. Cross-trait analyses revealed extensive genomic correlations between adiposity measures and obesity-related cancers. Pleiotropic analysis identified 464 pleiotropic loci and 409 unique candidate pleiotropic genes, 128 of which replicated in the transcriptome-wide association studies analysis. Gene-level analysis revealed potential shared biological mechanisms involving the brain-derived neurotrophic factor signaling pathway, WNT\/\u03b2-catenin signaling, and adipogenesis, whereas TWAS revealed their predominant expression in the digestive, nervous, and adipose tissues. Mendelian randomization analysis showed stronger associations between genetically increased BMI, WTH, and obesity-related cancers than other body fat distributions. Our study demonstrates that pleiotropic genetic determinants between adiposity and obesity-related cancers are widely distributed across the genome, reinforcing the hypothesis that adiposity increases cancer risk and revealing potential molecular pathways that may contribute to both adiposity and cancer development.<\/jats:p>","DOI":"10.1093\/bib\/bbaf439","type":"journal-article","created":{"date-parts":[[2025,8,28]],"date-time":"2025-08-28T12:20:43Z","timestamp":1756383643000},"source":"Crossref","is-referenced-by-count":2,"title":["Investigating the shared genetic architecture between adiposity measures and obesity-related cancers"],"prefix":"10.1093","volume":"26","author":[{"given":"Siyue","family":"Wang","sequence":"first","affiliation":[{"name":"Department of Epidemiology and Biostatistics and Ministry of Education Key Laboratory of Environment and Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology , 13 Hangkong Road, Qiaokou 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