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Functional informed genome-wide interaction analysis of body mass index, diabetes and colorectal cancer risk

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Functional informed genome-wide interaction analysis of body mass index, diabetes and colorectal cancer risk. / Xia, Zhiyu; Su, Yu-Ru; Petersen, Paneen; Qi, Lihong; Kim, Andre E; Figueiredo, Jane C; Lin, Yi; Nan, Hongmei; Sakoda, Lori C; Albanes, Demetrius; Berndt, Sonja I; Bézieau, Stéphane; Bien, Stephanie; Buchanan, Daniel D; Casey, Graham; Chan, Andrew T; Conti, David V; Drew, David A; Gallinger, Steven J; Gauderman, W James; Giles, Graham G; Gruber, Stephen B; Gunter, Marc J; Hoffmeister, Michael; Jenkins, Mark A; Joshi, Amit D; Le Marchand, Loic; Lewinger, Juan P; Li, Li; Lindor, Noralane M; Moreno, Victor; Murphy, Neil; Nassir, Rami; Newcomb, Polly A; Ogino, Shuji; Rennert, Gad; Song, Mingyang; Wang, Xiaoliang; Wolk, Alicja; Woods, Michael O; Brenner, Hermann; White, Emily; Slattery, Martha L; Giovannucci, Edward L; Chang-Claude, Jenny; Pharoah, Paul D P; Hsu, Li; Campbell, Peter T.

in: CANCER MED-US, Jahrgang 9, Nr. 10, 05.2020, S. 3563-3573.

Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung

Harvard

Xia, Z, Su, Y-R, Petersen, P, Qi, L, Kim, AE, Figueiredo, JC, Lin, Y, Nan, H, Sakoda, LC, Albanes, D, Berndt, SI, Bézieau, S, Bien, S, Buchanan, DD, Casey, G, Chan, AT, Conti, DV, Drew, DA, Gallinger, SJ, Gauderman, WJ, Giles, GG, Gruber, SB, Gunter, MJ, Hoffmeister, M, Jenkins, MA, Joshi, AD, Le Marchand, L, Lewinger, JP, Li, L, Lindor, NM, Moreno, V, Murphy, N, Nassir, R, Newcomb, PA, Ogino, S, Rennert, G, Song, M, Wang, X, Wolk, A, Woods, MO, Brenner, H, White, E, Slattery, ML, Giovannucci, EL, Chang-Claude, J, Pharoah, PDP, Hsu, L & Campbell, PT 2020, 'Functional informed genome-wide interaction analysis of body mass index, diabetes and colorectal cancer risk', CANCER MED-US, Jg. 9, Nr. 10, S. 3563-3573. https://doi.org/10.1002/cam4.2971

APA

Xia, Z., Su, Y-R., Petersen, P., Qi, L., Kim, A. E., Figueiredo, J. C., Lin, Y., Nan, H., Sakoda, L. C., Albanes, D., Berndt, S. I., Bézieau, S., Bien, S., Buchanan, D. D., Casey, G., Chan, A. T., Conti, D. V., Drew, D. A., Gallinger, S. J., ... Campbell, P. T. (2020). Functional informed genome-wide interaction analysis of body mass index, diabetes and colorectal cancer risk. CANCER MED-US, 9(10), 3563-3573. https://doi.org/10.1002/cam4.2971

Vancouver

Xia Z, Su Y-R, Petersen P, Qi L, Kim AE, Figueiredo JC et al. Functional informed genome-wide interaction analysis of body mass index, diabetes and colorectal cancer risk. CANCER MED-US. 2020 Mai;9(10):3563-3573. https://doi.org/10.1002/cam4.2971

Bibtex

@article{fe5403684c114abeb116ed48ce392d8b,
title = "Functional informed genome-wide interaction analysis of body mass index, diabetes and colorectal cancer risk",
abstract = "BACKGROUND: Body 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.METHODS: 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.RESULTS: 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 ).CONCLUSIONS: Aggregating G × E interactions and incorporating functional information, we discovered novel genes that may interact with BMI and diabetes on CRC risk.",
author = "Zhiyu Xia and Yu-Ru Su and Paneen Petersen and Lihong Qi and Kim, {Andre E} and Figueiredo, {Jane C} and Yi Lin and Hongmei Nan and Sakoda, {Lori C} and Demetrius Albanes and Berndt, {Sonja I} and St{\'e}phane B{\'e}zieau and Stephanie Bien and Buchanan, {Daniel D} and Graham Casey and Chan, {Andrew T} and Conti, {David V} and Drew, {David A} and Gallinger, {Steven J} and Gauderman, {W James} and Giles, {Graham G} and Gruber, {Stephen B} and Gunter, {Marc J} and Michael Hoffmeister and Jenkins, {Mark A} and Joshi, {Amit D} and {Le Marchand}, Loic and Lewinger, {Juan P} and Li Li and Lindor, {Noralane M} and Victor Moreno and Neil Murphy and Rami Nassir and Newcomb, {Polly A} and Shuji Ogino and Gad Rennert and Mingyang Song and Xiaoliang Wang and Alicja Wolk and Woods, {Michael O} and Hermann Brenner and Emily White and Slattery, {Martha L} and Giovannucci, {Edward L} and Jenny Chang-Claude and Pharoah, {Paul D P} and Li Hsu and Campbell, {Peter T}",
note = "{\textcopyright} 2020 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.",
year = "2020",
month = may,
doi = "10.1002/cam4.2971",
language = "English",
volume = "9",
pages = "3563--3573",
journal = "CANCER MED-US",
issn = "2045-7634",
publisher = "John Wiley and Sons Ltd",
number = "10",

}

RIS

TY - JOUR

T1 - Functional informed genome-wide interaction analysis of body mass index, diabetes and colorectal cancer risk

AU - Xia, Zhiyu

AU - Su, Yu-Ru

AU - Petersen, Paneen

AU - Qi, Lihong

AU - Kim, Andre E

AU - Figueiredo, Jane C

AU - Lin, Yi

AU - Nan, Hongmei

AU - Sakoda, Lori C

AU - Albanes, Demetrius

AU - Berndt, Sonja I

AU - Bézieau, Stéphane

AU - Bien, Stephanie

AU - Buchanan, Daniel D

AU - Casey, Graham

AU - Chan, Andrew T

AU - Conti, David V

AU - Drew, David A

AU - Gallinger, Steven J

AU - Gauderman, W James

AU - Giles, Graham G

AU - Gruber, Stephen B

AU - Gunter, Marc J

AU - Hoffmeister, Michael

AU - Jenkins, Mark A

AU - Joshi, Amit D

AU - Le Marchand, Loic

AU - Lewinger, Juan P

AU - Li, Li

AU - Lindor, Noralane M

AU - Moreno, Victor

AU - Murphy, Neil

AU - Nassir, Rami

AU - Newcomb, Polly A

AU - Ogino, Shuji

AU - Rennert, Gad

AU - Song, Mingyang

AU - Wang, Xiaoliang

AU - Wolk, Alicja

AU - Woods, Michael O

AU - Brenner, Hermann

AU - White, Emily

AU - Slattery, Martha L

AU - Giovannucci, Edward L

AU - Chang-Claude, Jenny

AU - Pharoah, Paul D P

AU - Hsu, Li

AU - Campbell, Peter T

N1 - © 2020 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.

PY - 2020/5

Y1 - 2020/5

N2 - BACKGROUND: Body 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.METHODS: 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.RESULTS: 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 ).CONCLUSIONS: Aggregating G × E interactions and incorporating functional information, we discovered novel genes that may interact with BMI and diabetes on CRC risk.

AB - BACKGROUND: Body 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.METHODS: 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.RESULTS: 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 ).CONCLUSIONS: Aggregating G × E interactions and incorporating functional information, we discovered novel genes that may interact with BMI and diabetes on CRC risk.

U2 - 10.1002/cam4.2971

DO - 10.1002/cam4.2971

M3 - SCORING: Journal article

C2 - 32207560

VL - 9

SP - 3563

EP - 3573

JO - CANCER MED-US

JF - CANCER MED-US

SN - 2045-7634

IS - 10

ER -