Peruchet-Noray, Laia and Sedlmeier, Anja M. and Dimou, Niki and Baurecht, Hansjoerg and Fervers, Beatrice and Fontvieille, Emma and Konzok, Julian and Tsilidis, Kostas K. and Christakoudi, Sofia and Jansana, Anna and Cordova, Reynalda and Bohmann, Patricia and Stein, Michael J. and Weber, Andrea and Bezieau, Stephane and Brenner, Hermann and Chan, Andrew T. and Cheng, Iona and Figueiredo, Jane C. and Garcia-Etxebarria, Koldo and Moreno, Victor and Newton, Christina C. and Schmit, Stephanie L. and Song, Mingyang and Ulrich, Cornelia M. and Ferrari, Pietro and Viallon, Vivian and Carreras-Torres, Robert and Gunter, Marc J. and Freisling, Heinz (2024) Tissue-specific genetic variation suggests distinct molecular pathways between body shape phenotypes and colorectal cancer. SCIENCE ADVANCES, 10 (16): eadj1987. ISSN 2375-2548,
Full text not available from this repository. (Request a copy)Abstract
It remains unknown whether adiposity subtypes are differentially associated with colorectal cancer (CRC). To move beyond single-trait anthropometric indicators, we derived four multi-trait body shape phenotypes reflecting adiposity subtypes from principal components analysis on body mass index, height, weight, waist-to-hip ratio, and waist and hip circumference. A generally obese (PC1) and a tall, centrally obese (PC3) body shape were both positively associated with CRC risk in observational analyses in 329,828 UK Biobank participants (3728 cases). In genome-wide association studies in 460,198 UK Biobank participants, we identified 3414 genetic variants across four body shapes and Mendelian randomization analyses confirmed positive associations of PC1 and PC3 with CRC risk (52,775 cases/45,940 controls from GECCO/CORECT/CCFR). Brain tissue-specific genetic instruments, mapped to PC1 through enrichment analysis, were responsible for the relationship between PC1 and CRC, while the relationship between PC3 and CRC was predominantly driven by adipose tissue-specific genetic instruments. This study suggests distinct putative causal pathways between adiposity subtypes and CRC.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | MENDELIAN RANDOMIZATION; R-PACKAGE; RISK; INSTRUMENTS; METAANALYSIS; OBESITY; DYSLIPIDEMIA; ASSOCIATION; SCORE; BIAS; |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Innere Medizin III (Hämatologie und Internistische Onkologie) Medicine > Institut für Epidemiologie und Präventivmedizin |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 14 Jan 2026 14:06 |
| Last Modified: | 14 Jan 2026 14:06 |
| URI: | https://pred.uni-regensburg.de/id/eprint/65347 |
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