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Environmental variables and genome-environment interactions predicting IBD diagnosis in large UK cohort.

ABSTRACT: A combination of genetic susceptibility and environmental exposure is thought to cause inflammatory bowel disease (IBD), but the non-genetic component remains poorly characterized. We therefore undertook a search for environmental variables and gene-environment interactions associated with future IBD diagnosis in a large UK cohort. Using self-report and electronic health records, we identified 1946 Crohn's disease (CD) and 3715 ulcerative colitis (UC) patients after quality control in the UK Biobank. Based on prior literature and biological plausibility , we tested 38 candidate environmental variables for association with CD, UC, and overall IBD using Cox proportional hazard regressions. We also tested whether these variables interacted with polygenic risk in predicting disease, following up significant (FDR < 0.05) results with tests for SNP-environment associations. We performed robustness analyses on all significant results. As in previous reports, appendectomy protected against UC, smoking (both current and previous) elevated risk for CD, current smoking protected against UC, and previous smoking imparted a risk for UC. Childhood antibiotic use associated with IBD, as did sun exposure during the winter. Socioeconomic deprivation was conferred a risk for IBD, CD, and UC. We uncovered negative interactions between polygenic risk and previous oral contraceptive use for IBD and UC. Polygenic risk also interacted negatively with previous smoking in predicting UC. There were no individually significant SNP-environment interactions. Thus, for a limited set of environmental variables, there was strong evidence of association with IBD diagnosis in the UK Biobank, and interaction with polygenic risk was minimal.

SUBMITTER: Yang AZ

PROVIDER: S-EPMC9240024 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:BACKGROUND:As direct acting antiviral (DAA) therapy is progressively rolled out for patients with hepatitis C virus (HCV) infection, careful scrutiny of HCV epidemiology, diagnostic testing, and access to care is crucial to underpin improvements in delivery of treatment, with the ultimate goal of elimination. METHODS:We retrospectively studied microbiology records from a large UK teaching hospital in order to compare the performance of HCV screening and diagnostic tests (antibody, antigen and HCV RNA detection). Having described a local cohort of adults with active HCV infection, we investigated the proportion who attended hospital appointments, were prescribed direct acting antiviral (DAA) therapy, and cleared HCV RNA following treatment. RESULTS:Over a total time period of 33 months between 2013 and 2016, we tested 38,509 individuals for HCV infection and confirmed a new diagnosis of active HCV infection (HCV-Ag + and/or HCV RNA+) in 353 (positive rate 0.9%). Our in-house HCV-Ab screening test had a positive predictive value of 87% compared to repeat HCV-Ab testing in a reference laboratory, highlighting the potential for false positives to arise using this test. HCV-Ag had 100% positive predictive value compared to detection of HCV RNA. There was a strong correlation between quantitative HCV-Ag and HCV RNA viral load (p < 0.0001). Among the cases of infection, genotype-1 and genotype-3 predominated, the median age was 37 years, 84% were male, and 36% were in prison. Hepatology review was provided in 39%, and 22% received treatment. Among those who received DAA therapy with 12 weeks of follow-up, 93% achieved a sustained virologic response (SVR12). CONCLUSIONS:HCV-Ag performs well as a diagnostic test compared to PCR for HCV RNA. Active HCV infection is over-represented among men and in the prison population. DAA therapy is successful in those who receive it, but a minority of patients with a diagnosis of HCV infection access clinical care. Enhanced efforts are required to provide linkage to clinical care within high risk populations.

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Environmental variables and genome-environment interactions predicting IBD diagnosis in large UK cohort.

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