Whole-exome sequencing for inflammatory bowel disease patients treated with biologic agents
Epidemiology and Medical Biometry/Statistics
Gastroenterology
Final Report Abstract
We performed whole-exome sequencing (WES) for IBD patients from studies RUNcd (headto-head comparison TNF inhibitors) and VEDOibd (head-to-head comparison vedolizumab/TNF inhibitors) at the Competence Centre for Genomic Analysis (CCGA) Kiel. Clinical remission outcomes were assessed at a primary response time point, i.e. the visit closest to 14 weeks after first use of biologics. We performed therapy-response WES single-marker association testing for 329 patients to identify response/nonresponse-associated genetic variants, separately for vedolizumab and anti-TNF treated patients. Since no significant association signal was found with genome-wide significance, we additionally performed genome-wide genotyping with the Illumina Global Screening Array (GSA; including non-coding variants) for the same patients at our own expense (non-DFG funds). One interesting association finding from the GSA-based analysis is the suggestive association of genetic variants at chr10q21.2 (ZNF365) previously reported for lung function (FEV1/COPD) and percentage mammographic density as listed in the NHGRI-EBI GWAS Catalog. Locus chr10q21.2 (ZNF365) is also interesting, as in our previous WES study for 139 Korean and 77 German anti-TNF treated patients with IBD we identified locus ZNF133 to be associated with response to infliximab (i.e. anti-TNF) for patients with IBD, indicating that genetic variation at zink finger protein-encoding genes may play a role in response to anti-TNF agents. These and other suggestive association signals need to be validated and functionally investigated in follow-up studies.
