SU30: RARE VARIANTS WITHIN LOCI HARBORING COMMON VARIANTS ASSOCIATED WITH BIPOLAR DISORDER AND SCHIZOPHRENIA: FURTHER ELUCIDATING THE GENETIC ARCHITECTURE OF SEVERE PSYCHIATRIC ILLNESS

Abstract

Background Bipolar Disorder (BP) and Schizophrenia (SZ) are common and genetically complex disorders characterized by often severe and overlapping symptoms. Although GWAS have identified several common variants increasing disease risk, a major portion of the heritability of both diseases has yet to be explained and may lie hidden in a collection of low-frequency, rare and ultra rare variants (MAF Methods Whole exomes of 186 individuals with a DSM-IV diagnose of type I BP and 173 individuals with a DSM-IV diagnosis of SZ were sequenced. Variants with MAF Results Burden testing (CAST) will be used to test for an overrepresentation of variants with MAF Discussion Through a combined approach of whole exome analysis and targeted resequencing, we hope to identify rare or ultra rare variants within the known GWAS loci, increasing an individual s risk of BP and SZ, as have been shown to exist for several other common complex genetic diseases. The identification of such variants would not only complete the picture of the genetic architecture of both disorders but could also provide a means to further explore the underlying pathophysiology through the development of more efficient animal models.