Parent of Origin Effects on Quantitative Phenotypes in a Founder Population

ABSTRACT The impact of the parental origin of associated alleles in GWAS has been largely ignored. Yet sequence variants could affect traits differently depending on whether they are inherited from the mother or the father. To explore this possibility, we studied 21 quantitative phenotypes in a large Hutterite pedigree. We first identified variants with significant single parent (maternal-only or paternal-only) effects, and then used a novel statistical model to identify variants with opposite parental effects. Overall, we identified parent of origin effects (POEs) on 11 phenotypes, most of which are risk factors for cardiovascular disease. Many of the loci with POEs have features of imprinted regions and many of the variants with POE are associated with the expression of nearby genes. Overall, our results indicate that POEs, which are often opposite in direction, are relatively common in humans, have potentially important clinical effects, and will be missed in traditional GWAS.