Summary Ulcerative colitis (UC) is a devastating immune-mediated disease that is on the rise globally. In our prior study, we found that Hispanics have less severe disease than non-Hispanics, but yet within one US-born generation develop a disease course that is similar. Differences in adoption of a Western diet between US- born and foreign-born Hispanics could explain differences in UC severity observed. A Western diet, high in n-6 to n-3 polyunsaturated fatty acids (PUFA), is up to 10-20 times the recommended intake and is considered pro- inflammatory. However, heterogeneity of results in dietary intervention studies suggests that underlying genetic variation in PUFA metabolism may modify diet effects. Our preliminary data indicates that Hispanics with UC have polymorphisms in PUFA not present in Hispanic controls. In UC, disease activity measured by rectal bleeding, number of bowel movements, and urgency correlates with endoscopic inflammation. I hypothesize that Hispanics with UC whose diet follows a higher Western dietary pattern, defined by a reproducible dietary pattern score, have more active disease, than those whose diet scores are lower. Further, I propose that carriage of PUFA variants augments the effect of a Western diet on relapse leading to a disproportionate pro- inflammatory effect of the diet. In this study, I examine the influence of a Western dietary pattern on remission and relapse of UC among Hispanics (Aim 1). We will test whether PUFA variants influence relapse and enhance the effect of a Western diet on UC relapse (Aim 2). A total of 320 self- identified, Hispanic participants with UC are followed at our GI clinics and we will include these for our diet portion in Aim 1. We will include a total of 691 Hispanics with UC and 900 Hispanic controls for our Aim 2 genetics portion. We have detailed demographic and clinical information on these patients, as well as whole genome sequencing of PUFA variants. Participants will be asked to complete a validated food-frequency dietary questionnaire, at baseline and at 1-year follow up. Disease activity using the validated simple clinical colitis activity index will be assessed at baseline and at 1 year follow up in combination with fecal calprotectin. We will calculate scores for a Western dietary pattern and determine the influence of diet on relapse using multivariable regression analysis. In Aim 2, we will examine the effect of PUFA variants on relapse and also determine gene-environment interactions influencing disease activity between PUFA variants and Western diet. Results gathered from this study will be a step towards personalizing IBD treatment by targeting specific dietary patterns i...