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000289650 1001_ $$00000-0001-8742-8920$$aPeruchet-Noray, Laia$$b0
000289650 245__ $$aTissue-specific genetic variation suggests distinct molecular pathways between body shape phenotypes and colorectal cancer.
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000289650 520__ $$aIt remains unknown whether adiposity subtypes are differentially associated with colorectal cancer (CRC). To move beyond single-trait anthropometric indicators, we derived four multi-trait body shape phenotypes reflecting adiposity subtypes from principal components analysis on body mass index, height, weight, waist-to-hip ratio, and waist and hip circumference. A generally obese (PC1) and a tall, centrally obese (PC3) body shape were both positively associated with CRC risk in observational analyses in 329,828 UK Biobank participants (3728 cases). In genome-wide association studies in 460,198 UK Biobank participants, we identified 3414 genetic variants across four body shapes and Mendelian randomization analyses confirmed positive associations of PC1 and PC3 with CRC risk (52,775 cases/45,940 controls from GECCO/CORECT/CCFR). Brain tissue-specific genetic instruments, mapped to PC1 through enrichment analysis, were responsible for the relationship between PC1 and CRC, while the relationship between PC3 and CRC was predominantly driven by adipose tissue-specific genetic instruments. This study suggests distinct putative causal pathways between adiposity subtypes and CRC.
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000289650 7001_ $$00000-0002-7564-3065$$aSedlmeier, Anja M$$b1
000289650 7001_ $$00000-0003-1678-9328$$aDimou, Niki$$b2
000289650 7001_ $$00000-0002-9265-5594$$aBaurecht, Hansjörg$$b3
000289650 7001_ $$00000-0003-3498-6499$$aFervers, Béatrice$$b4
000289650 7001_ $$aFontvieille, Emma$$b5
000289650 7001_ $$00000-0002-4232-4105$$aKonzok, Julian$$b6
000289650 7001_ $$00000-0002-8452-8472$$aTsilidis, Kostas K$$b7
000289650 7001_ $$aChristakoudi, Sofia$$b8
000289650 7001_ $$00000-0001-8504-1618$$aJansana, Anna$$b9
000289650 7001_ $$00000-0002-7781-6433$$aCordova, Reynalda$$b10
000289650 7001_ $$00000-0002-0931-8651$$aBohmann, Patricia$$b11
000289650 7001_ $$00000-0002-1120-1751$$aStein, Michael J$$b12
000289650 7001_ $$aWeber, Andrea$$b13
000289650 7001_ $$00000-0003-0095-1319$$aBézieau, Stéphane$$b14
000289650 7001_ $$0P:(DE-He78)90d5535ff896e70eed81f4a4f6f22ae2$$aBrenner, Hermann$$b15$$udkfz
000289650 7001_ $$00000-0001-7284-6767$$aChan, Andrew T$$b16
000289650 7001_ $$aCheng, Iona$$b17
000289650 7001_ $$aFigueiredo, Jane C$$b18
000289650 7001_ $$00000-0002-6107-9416$$aGarcia-Etxebarria, Koldo$$b19
000289650 7001_ $$00000-0002-2818-5487$$aMoreno, Victor$$b20
000289650 7001_ $$00000-0003-1471-5608$$aNewton, Christina C$$b21
000289650 7001_ $$00000-0001-5931-1194$$aSchmit, Stephanie L$$b22
000289650 7001_ $$00000-0002-1324-0316$$aSong, Mingyang$$b23
000289650 7001_ $$00000-0001-7641-059X$$aUlrich, Cornelia M$$b24
000289650 7001_ $$00000-0001-9358-7338$$aFerrari, Pietro$$b25
000289650 7001_ $$00000-0002-9799-4421$$aViallon, Vivian$$b26
000289650 7001_ $$00000-0002-2925-734X$$aCarreras-Torres, Robert$$b27
000289650 7001_ $$00000-0001-5472-6761$$aGunter, Marc J$$b28
000289650 7001_ $$00000-0001-8648-4998$$aFreisling, Heinz$$b29
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