Tissue-specific genetic variation suggests distinct molecular pathways between body shape phenotypes and colorectal cancer

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, heig...

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Detalhes bibliográficos
Autores: Peruchet Noray, Laia, Sedlmeier, Anja M., Dimou, Niki, Baurecht, Hansjörg, Fervers, Béatrice, Fontvieille, Emma, Konzok, Julian, Tsilidis, Kostas K., Christakoudi, Sofia, Jansana, Anna, Cordova, Reynalda, Bohmann, Patricia, Stein, Michael J., Weber, Andrea, Bézieau, Stéphane, Brenner, Hermann, Chan, Andrew T., Cheng, Iona, Figueiredo, Jane C., Garcia Etxebarria, Koldo, Moreno Aguado, Víctor, Newton, Christina C., Schmit, Stephanie L., Song, Mingyang, Ulrich, Cornelia M., Ferrari, Pietro, Viallon, Vivian, Carreras Torres, Robert, Gunter, Marc J., Freisling, Heinz
Formato: artículo
Estado:Versión publicada
Fecha de publicación:2024
País:España
Recursos:Universidad de Barcelona
Repositorio:Dipòsit Digital de la UB
OAI Identifier:oai:diposit.ub.edu:2445/214209
Acesso em linha:https://hdl.handle.net/2445/214209
Access Level:acceso abierto
Palavra-chave:Càncer colorectal
Genètica mèdica
Colorectal cancer
Medical genetics
Descrição
Resumo: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.

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