Publication Date:
2021-02-18
Description:
Background Epidemiological studies have long recognized risky behaviors as potentially modifiable factors for onset and flares of inflammatory bowel disease (IBD); yet the underlying mechanisms are largely unknown. Recently, the genetic susceptibilities to cigarette smoking, alcohol and cannabis use (i.e. substance use [SU]) have been characterized by well-powered genome-wide association studies (GWAS). We aimed to assess the impact of genetic determinants of SU on IBD risk. Methods Using Mount Sinai Crohn and Colitis Registry (MSCCR) cohort of 1058 IBD cases and 188 healthy controls, we computed polygenic risk score (PRS) for SU, and correlated them with observed IBD diagnoses, while adjusting for genetic ancestry, PRS for IBD and SU behavior at enrollment. The results were validated in a pediatric cohort with no SU exposure. Results PRS of alcohol consumption (DrnkWk), smoking cessation, and age of smoking initiation, were associated with IBD risk in MSCCR, even after adjustment for PRSIBD and actual smoking status. One interquartile range decrease in PRSDrnkWk was significantly associated to higher IBD risk (ie, inverse association) with OR = 1.65 and 95%CI: 1.32, 2.06). The association was replicated in a pediatric CD cohort. Colocalization analysis identified a locus on chromosome 16 with polymorphisms in IL27, SULT1A2, and SH2B1, that reached genome-wide statistical significance in GWAS (p
Print ISSN:
0964-6906
Electronic ISSN:
1460-2083
Topics:
Biology
,
Medicine
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