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000154193 1001_ $$00000-0002-8340-8508$$aXia, Zhiyu$$b0
000154193 245__ $$aFunctional informed genome-wide interaction analysis of body mass index, diabetes and colorectal cancer risk.
000154193 260__ $$aHoboken, NJ$$bWiley$$c2020
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000154193 500__ $$a2020 May;9(10):3563-3573
000154193 520__ $$aBody mass index (BMI) and diabetes are established risk factors for colorectal cancer (CRC), likely through perturbations in metabolic traits (e.g. insulin resistance and glucose homeostasis). Identification of interactions between variation in genes and these metabolic risk factors may identify novel biologic insights into CRC etiology.To improve statistical power and interpretation for gene-environment interaction (G × E) testing, we tested genetic variants that regulate expression of a gene together for interaction with BMI (kg/m2 ) and diabetes on CRC risk among 26 017 cases and 20 692 controls. Each variant was weighted based on PrediXcan analysis of gene expression data from colon tissue generated in the Genotype-Tissue Expression Project for all genes with heritability ≥1%. We used a mixed-effects model to jointly measure the G × E interaction in a gene by partitioning the interactions into the predicted gene expression levels (fixed effects), and residual G × E effects (random effects). G × BMI analyses were stratified by sex as BMI-CRC associations differ by sex. We used false discovery rates to account for multiple comparisons and reported all results with FDR <0.2.Among 4839 genes tested, genetically predicted expressions of FOXA1 (P = 3.15 × 10-5 ), PSMC5 (P = 4.51 × 10-4 ) and CD33 (P = 2.71 × 10-4 ) modified the association of BMI on CRC risk for men; KIAA0753 (P = 2.29 × 10-5 ) and SCN1B (P = 2.76 × 10-4 ) modified the association of BMI on CRC risk for women; and PTPN2 modified the association between diabetes and CRC risk in both sexes (P = 2.31 × 10-5 ).Aggregating G × E interactions and incorporating functional information, we discovered novel genes that may interact with BMI and diabetes on CRC risk.
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000154193 7001_ $$aSu, Yu-Ru$$b1
000154193 7001_ $$aPetersen, Paneen$$b2
000154193 7001_ $$aQi, Lihong$$b3
000154193 7001_ $$aKim, Andre E$$b4
000154193 7001_ $$00000-0003-1217-5249$$a}, , USC Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.$$b5
000154193 7001_ $$aFigueiredo, Jane C$$b6
000154193 7001_ $$a}, , USC Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA. | Department of Medicine, Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, CA, USA.$$b7
000154193 7001_ $$aLin, Yi$$b8
000154193 7001_ $$aNan, Hongmei$$b9
000154193 7001_ $$aSakoda, Lori C$$b10
000154193 7001_ $$aAlbanes, Demetrius$$b11
000154193 7001_ $$aBerndt, Sonja I$$b12
000154193 7001_ $$aBézieau, Stéphane$$b13
000154193 7001_ $$aBien, Stephanie$$b14
000154193 7001_ $$00000-0003-2225-6675$$aBuchanan, Daniel D$$b15
000154193 7001_ $$aCasey, Graham$$b16
000154193 7001_ $$aChan, Andrew T$$b17
000154193 7001_ $$aConti, David V$$b18
000154193 7001_ $$a}, , USC Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.$$b19
000154193 7001_ $$aDrew, David A$$b20
000154193 7001_ $$aGallinger, Steven J$$b21
000154193 7001_ $$aGauderman, W James$$b22
000154193 7001_ $$a}, , USC Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.$$b23
000154193 7001_ $$aGiles, Graham G$$b24
000154193 7001_ $$aGruber, Stephen B$$b25
000154193 7001_ $$a}, , USC Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.$$b26
000154193 7001_ $$aGunter, Marc J$$b27
000154193 7001_ $$0P:(DE-He78)6c5d058b7552d071a7fa4c5e943fff0f$$aHoffmeister, Michael$$b28$$udkfz
000154193 7001_ $$aJenkins, Mark A$$b29
000154193 7001_ $$aJoshi, Amit D$$b30
000154193 7001_ $$aLe Marchand, Loic$$b31
000154193 7001_ $$aLewinger, Juan P$$b32
000154193 7001_ $$a}, , USC Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.$$b33
000154193 7001_ $$aLi, Li$$b34
000154193 7001_ $$aLindor, Noralane M$$b35
000154193 7001_ $$aMoreno, Victor$$b36
000154193 7001_ $$aMurphy, Neil$$b37
000154193 7001_ $$aNassir, Rami$$b38
000154193 7001_ $$aNewcomb, Polly A$$b39
000154193 7001_ $$aOgino, Shuji$$b40
000154193 7001_ $$aRennert, Gad$$b41
000154193 7001_ $$aSong, Mingyang$$b42
000154193 7001_ $$aWang, Xiaoliang$$b43
000154193 7001_ $$aWolk, Alicja$$b44
000154193 7001_ $$aWoods, Michael O$$b45
000154193 7001_ $$0P:(DE-He78)90d5535ff896e70eed81f4a4f6f22ae2$$aBrenner, Hermann$$b46$$udkfz
000154193 7001_ $$aWhite, Emily$$b47
000154193 7001_ $$aSlattery, Martha L$$b48
000154193 7001_ $$aGiovannucci, Edward L$$b49
000154193 7001_ $$0P:(DE-He78)c259d6cc99edf5c7bc7ce22c7f87c253$$aChang-Claude, Jenny$$b50$$udkfz
000154193 7001_ $$aPharoah, Paul D P$$b51
000154193 7001_ $$aHsu, Li$$b52
000154193 7001_ $$aCampbell, Peter T$$b53
000154193 7001_ $$aPeters, Ulrike$$b54
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