Fine Mapping Regions of Excess Homozygosity-by-descent in Palau

Schizophrenia is a devastating psychiatric disorder that affects approximately 1% of the general population. Its complexity and enigmatic etiology place an economic and social burden on public health resources, while causing emotional distress for patients and their families. Twin, family, and adoption studies have shown evidence for a genetic component, but its complex pattern of inheritance has complicated the efforts for identifying susceptibility genes. The discovery of disease causing genes has public health relevance given that it could lead the path to presymptomatic testing, preventative care, and a better prognosis. Recent studies have shown that inbreeding, through consanguineous marriages, is associated with increased risk for schizophrenia. In the genetically isolated island of Palau, the prevalence of schizophrenia is more than doubled at 2.7%. Here, we examine the role of excess homozygosity and regions of homozygosity-by-descent on schizophrenia risk in Palau. Palauans practice exogamy, but the likely limited size of the founding population, combined with recent population bottlenecks, ensures that homozygous segments of the genome, shared identical-by-descent from a common ancestor, occur regularly in Palauan genomes. Five gene regions, RAB3GAP2, MARK1, DISC1, FAM184A, and IGSF9B were found to overlap segments that were commonly shared among subjects who were homozygous-by-descent. Cases and controls that were homozygous for these regions were counted and compared, with heightened representation from cases. Further SNP FINE MAPPING REGIONS OF EXCESS HOMOZYGOSITY-BY-DESCENT IN PALAU Cara S. Dresbold, MS University of Pittsburgh, 2013