Tissue-specific genetic variation suggests distinct molecular pathways between body shape phenotypes and colorectal cancer
- Author(s)
- Laia Peruchet-Noray, Anja M Sedlmeier, Niki Dimou, Hansjörg Baurecht, Béatrice Fervers, Emma Fontvieille, Julian Konzok, Kostas K Tsilidis, Sofia Christakoudi, Anna Jansana, Reynalda Cordova, Patricia Bohmann, Michael J Stein, Andrea Weber, Stéphane Bézieau, Hermann Brenner, Andrew T Chan, Iona Cheng, Jane C Figueiredo, Koldo Garcia-Etxebarria, Victor Moreno, Christina C Newton, Stephanie L Schmit, Mingyang Song, Cornelia M Ulrich, Pietro Ferrari, Vivian Viallon, Robert Carreras-Torres, Marc J Gunter, Heinz Freisling
- 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.
- Organisation(s)
- Department of Economics
- External organisation(s)
- University of Barcelona, University Hospital Regensburg, International Agency for Research on Cancer (IARC-WHO), Department Cancer Environment Center Léon Bérard, University of Ioannina, King's College London, Universität Hamburg, Centre hospitalier universitaire de Nantes, Stiftung Deutsches Krebsforschungszentrum, Massachussetts General Hospital, University of California, San Francisco, Cedars-Sinai Medical Center, Centro de Investigación Biomédica en Red (CIBERehd), Consortium for Biomedical Research in Epidemiology and Public Health (CIBERESP), American Cancer Society, Case Western Reserve University, Harvard T.H. Chan School of Public Health, University of Utah, Instituto de Investigación Biomédica de Girona Josep Trueta, Imperial College London
- Journal
- Science Advances
- Volume
- 10
- Pages
- eadj1987
- ISSN
- 2375-2548
- DOI
- https://doi.org/10.1126/sciadv.adj1987
- Publication date
- 04-2024
- Peer reviewed
- Yes
- Austrian Fields of Science 2012
- 303007 Epidemiology, 303025 Preventive medicine
- Keywords
- Sustainable Development Goals
- SDG 3 - Good Health and Well-being
- Portal url
- https://ucrisportal.univie.ac.at/en/publications/9d78cfae-058b-444f-92aa-f53556d2b594