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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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
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2024
País:España
Institución:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
Repositorio:Recercat. Dipósit de la Recerca de Catalunya
OAI Identifier:oai:recercat.cat:2445/214209
Acceso en línea:https://hdl.handle.net/2445/214209
Access Level:acceso abierto
Palabra clave:Càncer colorectal
Genètica mèdica
Colorectal cancer
Medical genetics
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spelling Tissue-specific genetic variation suggests distinct molecular pathways between body shape phenotypes and colorectal cancerPeruchet Noray, LaiaSedlmeier, Anja M.Dimou, NikiBaurecht, HansjörgFervers, BéatriceFontvieille, EmmaKonzok, JulianTsilidis, Kostas K.Christakoudi, SofiaJansana, AnnaCordova, ReynaldaBohmann, PatriciaStein, Michael J.Weber, AndreaBézieau, StéphaneBrenner, HermannChan, Andrew T.Cheng, IonaFigueiredo, Jane C.Garcia Etxebarria, KoldoMoreno Aguado, VíctorNewton, Christina C.Schmit, Stephanie L.Song, MingyangUlrich, Cornelia M.Ferrari, PietroViallon, VivianCarreras Torres, RobertGunter, Marc J.Freisling, HeinzCàncer colorectalGenètica mèdicaColorectal cancerMedical geneticsIt 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.American Association for the Advancement of Science (AAAS)2024202420242024info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersion15 p.application/pdfhttps://hdl.handle.net/2445/214209Articles publicats en revistes (Institut d'lnvestigació Biomèdica de Bellvitge (IDIBELL))reponame:Recercat. Dipósit de la Recerca de Catalunyainstname:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)InglésReproducció del document publicat a: https://doi.org/10.1126/sciadv.adj1987Science Advances, 2024, vol. 10, num. 16https://doi.org/10.1126/sciadv.adj1987cc by-nc (c) Peruchet Noray, Laia et al, 2024http://creativecommons.org/licenses/by-nc/3.0/es/info:eu-repo/semantics/openAccessoai:recercat.cat:2445/2142092026-05-29T05:05:01Z
dc.title.none.fl_str_mv Tissue-specific genetic variation suggests distinct molecular pathways between body shape phenotypes and colorectal cancer
title Tissue-specific genetic variation suggests distinct molecular pathways between body shape phenotypes and colorectal cancer
spellingShingle Tissue-specific genetic variation suggests distinct molecular pathways between body shape phenotypes and colorectal cancer
Peruchet Noray, Laia
Càncer colorectal
Genètica mèdica
Colorectal cancer
Medical genetics
title_short Tissue-specific genetic variation suggests distinct molecular pathways between body shape phenotypes and colorectal cancer
title_full Tissue-specific genetic variation suggests distinct molecular pathways between body shape phenotypes and colorectal cancer
title_fullStr Tissue-specific genetic variation suggests distinct molecular pathways between body shape phenotypes and colorectal cancer
title_full_unstemmed Tissue-specific genetic variation suggests distinct molecular pathways between body shape phenotypes and colorectal cancer
title_sort Tissue-specific genetic variation suggests distinct molecular pathways between body shape phenotypes and colorectal cancer
dc.creator.none.fl_str_mv 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
author Peruchet Noray, Laia
author_facet 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
author_role author
author2 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
author2_role author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Càncer colorectal
Genètica mèdica
Colorectal cancer
Medical genetics
topic Càncer colorectal
Genètica mèdica
Colorectal cancer
Medical genetics
description 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.
publishDate 2024
dc.date.none.fl_str_mv 2024
2024
2024
2024
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv https://hdl.handle.net/2445/214209
url https://hdl.handle.net/2445/214209
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv Reproducció del document publicat a: https://doi.org/10.1126/sciadv.adj1987
Science Advances, 2024, vol. 10, num. 16
https://doi.org/10.1126/sciadv.adj1987
dc.rights.none.fl_str_mv cc by-nc (c) Peruchet Noray, Laia et al, 2024
http://creativecommons.org/licenses/by-nc/3.0/es/
info:eu-repo/semantics/openAccess
rights_invalid_str_mv cc by-nc (c) Peruchet Noray, Laia et al, 2024
http://creativecommons.org/licenses/by-nc/3.0/es/
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv 15 p.
application/pdf
dc.publisher.none.fl_str_mv American Association for the Advancement of Science (AAAS)
publisher.none.fl_str_mv American Association for the Advancement of Science (AAAS)
dc.source.none.fl_str_mv Articles publicats en revistes (Institut d'lnvestigació Biomèdica de Bellvitge (IDIBELL))
reponame:Recercat. Dipósit de la Recerca de Catalunya
instname:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
instname_str Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
reponame_str Recercat. Dipósit de la Recerca de Catalunya
collection Recercat. Dipósit de la Recerca de Catalunya
repository.name.fl_str_mv
repository.mail.fl_str_mv
_version_ 1869404485828214784
score 15,812455

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