DMS Statistics and Data Science Seminar

Speaker: Dr. Jiwon Park (postdoctoral researcher, Department of Epidemiology, Johns Hopkins University)

Title: A Robust Pleiotropy Testing Method with Applications to Inflammatory Bowel Disease Subtypes with Sample Overlap

Abstract: Pleiotropy, where a genetic region influences multiple traits, is common in complex diseases and provides insight into shared biological mechanisms. However, identifying pleiotropic loci remains challenging, especially for correlated traits or case-control studies with overlapping samples. We present PLACO+, a statistical method for detecting pleiotropic associations using GWAS summary statistics from two traits. PLACO+ models a composite null hypothesis with an inflated variance structure, allowing for partial associations, and computes analytical p-values based on the distribution of the product of correlated Z-scores. Applied to genome-wide studies of inflammatory bowel disease (IBD) subtypes—Crohn’s disease and ulcerative colitis—PLACO+ identifies shared genetic loci missed by conventional approaches, particularly when effects are in opposite directions. These results demonstrate the utility of PLACO+ in uncovering novel pleiotropic signals in complex trait genetics.