TY - JOUR
T1 - The contribution of genetic risk and lifestyle factors in the development of adult-onset inflammatory bowel disease
T2 - a prospective cohort study
AU - Sun, Yuhao
AU - Yuan, Shuai
AU - Chen, Xuejie
AU - Sun, Jing
AU - Kalla, Rahul
AU - Yu, Lili
AU - Wang, Lijuan
AU - Zhou, Xuan
AU - Kong, Xiangxing
AU - Hesketh, Therese
AU - Ho, Gwo-Tzer
AU - Ding, Kefeng
AU - Dunlop, Malcolm G
AU - Larsson, Susanna C.
AU - Satsangi, Jack
AU - Chen, Jie
AU - Wang, Xiaoyan
AU - Li, Xue
AU - Theodoratou, Evropi
AU - Giovannucci, Edward L
N1 - Funding Information:
Financial support: X.L.: the Natural Science Fund for Distinguished Young Scholars of Zhejiang Province (LR22H260001). X.Y.W.: National Natural Science Foundation of China (81970494) and Key Project of Research and Development Plan of Hunan Province(2019SK2041). S.C.L.: the Swedish Heart-Lung Foundation (Hjärt-Lungfonden, 20210351), the Swedish Research Council (Vetenskapsrådet, 2019-00977), and the Swedish Cancer Society (Cancerfonden). E.T.: CRUK Career Development Fellowship (C31250/A22804). K.F.D.: Project of the regional diagnosis and treatment center of the Health Planning Committee (No. JBZX-201903).
Publisher Copyright:
© 2023 Wolters Kluwer Health. All rights reserved.
PY - 2023/3/1
Y1 - 2023/3/1
N2 - INTRODUCTION: The joint associations across genetic risk, modifiable lifestyle factors, and inflammatory bowel disease (IBD) remains unclear.METHODS: Genetic susceptibility to Crohn's disease (CD) and ulcerative colitis (UC) was estimated by polygenic risk scores and further categorized into high, intermediate, and low genetic risk categories. Weighted healthy lifestyle scores were constructed based on 5 common lifestyle factors and categorized into favorable (4 or 5 healthy lifestyle factors), intermediate (3 healthy lifestyle factors), and unfavorable (0-2 healthy lifestyle factors) groups. Cox proportional hazards regression model was used to estimate the hazard ratios (HR) and 95% confidence interval (CI) for their associations.RESULTS: During the 12-year follow-up, 707 cases with CD and 1576 cases with UC were diagnosed in the UK Biobank cohort. Genetic risk and unhealthy lifestyle categories were monotonically associated with CD and UC risk with no multiplicative interaction between them. The HR of CD and UC were 2.24 (95% CI 1.75-2.86) and 2.15 (95% CI 1.82-2.53) for those with a high genetic risk, respectively. The HR of CD and UC for individuals with an unfavorable lifestyle were 1.94 (95% CI 1.61-2.33) and 1.98 (95% CI 1.73-2.27), respectively. The HR of individuals with a high genetic risk but a favorable lifestyle (2.33, 95% CI 1.58-3.44 for CD, and 2.05, 95% CI 1.58-2.66 for UC) were reduced nearly by half, compared with those with a high genetic risk but an unfavorable lifestyle (4.40, 95% CI 2.91-6.66 for CD and 4.44, 95% CI 3.34-5.91 for UC).DISCUSSION: Genetic and lifestyle factors were independently associated with susceptibility to incident CD and UC. Adherence to a favorable lifestyle was associated with a nearly 50% lower risk of CD and UC among participants at a high genetic risk.
AB - INTRODUCTION: The joint associations across genetic risk, modifiable lifestyle factors, and inflammatory bowel disease (IBD) remains unclear.METHODS: Genetic susceptibility to Crohn's disease (CD) and ulcerative colitis (UC) was estimated by polygenic risk scores and further categorized into high, intermediate, and low genetic risk categories. Weighted healthy lifestyle scores were constructed based on 5 common lifestyle factors and categorized into favorable (4 or 5 healthy lifestyle factors), intermediate (3 healthy lifestyle factors), and unfavorable (0-2 healthy lifestyle factors) groups. Cox proportional hazards regression model was used to estimate the hazard ratios (HR) and 95% confidence interval (CI) for their associations.RESULTS: During the 12-year follow-up, 707 cases with CD and 1576 cases with UC were diagnosed in the UK Biobank cohort. Genetic risk and unhealthy lifestyle categories were monotonically associated with CD and UC risk with no multiplicative interaction between them. The HR of CD and UC were 2.24 (95% CI 1.75-2.86) and 2.15 (95% CI 1.82-2.53) for those with a high genetic risk, respectively. The HR of CD and UC for individuals with an unfavorable lifestyle were 1.94 (95% CI 1.61-2.33) and 1.98 (95% CI 1.73-2.27), respectively. The HR of individuals with a high genetic risk but a favorable lifestyle (2.33, 95% CI 1.58-3.44 for CD, and 2.05, 95% CI 1.58-2.66 for UC) were reduced nearly by half, compared with those with a high genetic risk but an unfavorable lifestyle (4.40, 95% CI 2.91-6.66 for CD and 4.44, 95% CI 3.34-5.91 for UC).DISCUSSION: Genetic and lifestyle factors were independently associated with susceptibility to incident CD and UC. Adherence to a favorable lifestyle was associated with a nearly 50% lower risk of CD and UC among participants at a high genetic risk.
U2 - 10.14309/ajg.0000000000002180
DO - 10.14309/ajg.0000000000002180
M3 - Article
C2 - 36695739
SN - 0002-9270
VL - 118
SP - 511
EP - 522
JO - The American Journal of Gastroenterology
JF - The American Journal of Gastroenterology
IS - 3
ER -