Abstracts of the XXV World Congress of Psychiatric Genetics (WCPG)_ Oral Abstracts

s of the XXV World Congress of Psychiatric Genetics (WCPG): Oral Abstracts Saturday, October 14, 2017 Saturday Afternoon Oral Session: Schizophrenia 1:30 p.m. 3:00 p.m. 1. USING GENETIC DIVERSITY FROM EAST ASIA TO IMPROVE THE BIOLOGICAL INSIGHT INTO SCHIZOPHRENIA Hailiang Huang, Max Lam n, Chia-Yen Chen, Alicia Martin, Zhiqiang Li, Stephan Ripke, Michael O'Donovan, Mark Daly, Psychiatric Genomics Consortium Institute of Mental Health Massachusetts General Hospital Bio-X Institute Cardiff University Analytic and Translational Genetics Unit Asian Schizophrenia Working Group Background: Schizophrenia is a chronic and disabling psychiatric disorder affecting about 1% of the world population. While the biological mechanisms of schizophrenia remain largely elusive, much progress has been made in schizophrenia genetics in the past few years, with over 100 genomic loci associated with schizophrenia reported by the recent large-scale genome-wide association study. However, to date, almost all large schizophrenia genetics studies are derived from primarily European descent population, severely limiting our understanding of schizophrenia biology. Methods: Here we present a large-scale schizophrenia genetic study, comprising of 12 schizophrenia case-control cohorts from Singapore, Hong Kong, Taiwan, mainland China, Japan, and Indonesia. After quality control, there are 13,760 cases and 16,883 controls available for genome-wide association. A fixed effect meta-analysis across Asian and Caucasian populations was conducted resulting in a combined sample of 46,945 cases and 59,800 controls. A novel finemapping algorithm was designed and conducted to identify potential causal variants between Caucasian and Asian samples. Results: Twelve loci (po5e-8) were found associated with schizophrenia in the Asian sample. Six were previously associated with schizophrenia, and four are novel. An example is a new locus (Caucasians 0.7%; Asians 45%), which may have been previously missed, implicates CACNA2D2, a calcium channel auxiliary subunit associated with early infantile epileptic encephalopathy. Meta-analysis across Asian and Caucasian populations identified 40 new loci implicated in schizophrenia. Genetic effects are consistent in both populations. Using a published fine-mapping method and a European-only dataset, we mapped 11 schizophrenia associations to a credible set of r5 variants. The number increased to 18 associations when we used the novel finemapping algorithm on a combined European and Asian dataset, demonstrating a significantly improved association resolution. Discussion: The reported results consist of amongst the largest collection of Asian GWAS samples to date. Evidence indicates shared biology across major world populations in schizophrenia. Specifically, across the two populations, all known schizophrenia associations were congruent in effect directions, and effect sizes show no significant heterogeneity. Our approach not only serve to improve detection of common variant loci that implicates two major populations in the world, the approach we have undertaken, improved GWA resolution which in turn allows us to better isolate the causal alleles and facilitate the functional interpretation of schizophrenia associations. Disclosure: Nothing to disclose. http://dx.doi.org/10.1016/j.euroneuro.2017.08.002