Progress in genome-wide association studies of schizophrenia in Han Chinese populations

Abstract

Since 2006, genome-wide association studies of schizophrenia have led to the identification of numerous novel risk loci for this disease. However, there remains a geographical imbalance in genome-wide association studies, which to date have primarily focused on Western populations. During the last 6 years, genome-wide association studies in Han Chinese populations have identified both the sharing of susceptible loci across ethnicities and genes unique to Han Chinese populations. Here, we review recent progress in genome-wide association studies of schizophrenia in Han Chinese populations. Researchers have identified and replicated the sharing of susceptible genes, such as within the major histocompatibility complex, microRNA 137 (MIR137), zinc finger protein 804A (ZNF804A), vaccinia related kinase 2 (VRK2), and arsenite methyltransferase (AS3MT), across both European and East Asian populations. Several copy number variations identified in European populations have also been validated in the Han Chinese, including duplications at 16p11.2, 15q11.2-13.1, 7q11.23, and VIPR2 and deletions at 22q11.2, 1q21.1-q21.2, and NRXN1. However, these studies have identified some potential confounding factors, such as genetic heterogeneity and the effects of natural selection on tetraspanin 18 (TSPAN18) or zinc finger protein 323 (ZNF323), which may explain the population differences in genome-wide association studies. In the future, genome-wide association studies in Han Chinese populations should include meta-analyzes or mega-analyses with enlarged sample sizes across populations, deep sequencing, precision medicine treatment, and functional exploration of the risk genes for schizophrenia.

Fig. 1

Flow chart unraveling causal genes of schizophrenia from GWAS risk loci across multi-ethnicities