Psychiatric Genomics Consortium – Genetic Architecture Of Schizophrenia In Asian Populations

Abstract

Background During the past years, significant progress has been made to understand the genetic architecture of schizophrenia, with 108 loci spanning across the human genome demonstrated to be significantly associated with the illness. To date, there have been several follow-up reports investigating the biological functions of these loci and their impact on schizophrenia. Nevertheless, a majority of previously reported samples were of European descent, and it is currently unclear whether the genetic architecture of schizophrenia across populations would be similar. Here we present the PGC schizophrenia Asia initiative, a large-scale schizophrenia genetics study to systematically examine the schizophrenia genetic architecture in the non-European population. Methods Schizophrenia cases and controls from Singapore, Hong Kong, Taiwan, mainland China, Japan, and Indonesia are consolidated for the Asian genome-wide association analysis. A total sample size of N = 42,400 (Ncases=17,400; Ncontrols=25,000) are projected for analysis. Standard quality control procedures for genome-wide analysis are carried out via the Ricopili pipeline. Population outliers are examined via principal components analysis. Imputation for each cohort is carried out for the 1000 genomes phase 3 reference panel. Results Planned Analysis: Heterogeneity analysis will be conducted via meta-analytic and mega-analytic approaches and compared against summary statistics of Ncases=33,640; Ncontrols=43,456 European-descent samples from the most recent PGC SCZ meta analysis. Genetic correlation between European and Asian schizophrenia will also be conducted using popcorn, a version of LD regression that allows cross-population comparisons. Discussion The current effort to examine the genetic architecture of schizophrenia in Asian subjects aims to inform if the biological underpinnings of schizophrenia are different across the population, fine-map known loci and allow further novel loci associated with schizophrenia to be discovered through deep replication.