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.

Altered Expression Profile of IgLON Family of Neural Cell Adhesion Molecules in the Dorsolateral Prefrontal Cortex of Schizophrenic Patients

“…Schizophrenic patients have a reduced quality of life, significant functional impairment and suicide rates among schizophrenic patients remain alarmingly high ( Pompili et al, 2007 ). High heritability of schizophrenia has been consistently demonstrated by family studies ( Mäki et al, 2005 ) and genome-wide association studies have identified numerous risk chromosome loci candidates for schizophrenia ( O’Donovan et al, 2008 ; Purcell et al, 2009 ; Stefansson et al, 2009 ; Ripke et al, 2013 , 2014 ; Yue et al, 2017 ) indicating many common gene variants providing subtle effects ( Giusti-Rodríguez and Sullivan, 2013 ). Evidence from GWAS and studies revealing differentially expressed proteins in schizophrenia suggests that the majority of the pathophysiological processes underlying schizophrenia are involved in neuronal transmission, synaptic maturation and plasticity, neurite outgrowth and neurogenesis ( Hosak et al, 2012 ; Nascimento and Martins-de-Souza, 2015 ; Singh et al, 2017 ).…”

Genome-wide association studies in schizophrenia: Recent advances, challenges and future perspective

“…More substantial GWAS in Asian populations have gradually emerged over the past decade, with discovery sample sizes progressing from less than a thousand cases in some of the earliest studies (Ikeda et al, 2011;Yue et al, 2011) to over 13,000 in the most recent PGC analysis (Lam et al, 2018). The findings from schizophrenia GWAS in Asian populations have been broadly consistent with those of European populations (Yue et al, 2017). A recent study meta-analysed results from 8723 cases of Han Chinese ancestry and found associations at three loci, all of which had previously been found in European samples .…”

Evaluation of the relationship between VRK2, rs4380187 polymorphisms, and genetic susceptibility to schizophrenia in the Chinese Han population

“…Alkelai et al found that eight SNPs located in six genes ( LRRFIP1 , ACSL3 , LOC645434/NMBR , EFHD1 , UGT1A1 , and TWIST2 ) were associated with SZ in the Arab population of Israel 5 . Subsequent epidemiological studies reported that the heritability of SZ in Chinese population was approximately 63–78% 6 . Yue et al found two SNPs, viz.…”

“…5 Subsequent epidemiological studies reported that the heritability of SZ in Chinese population was approximately 63-78%. 6 Yue et al found two SNPs, viz. loc392301 and loc729457, in the Chinese Han population and replicated six SNP associations, including the apoptosis regulator, epigenetic PGBD1 and TSPAN18 genes, as well as neurodevelopmental ZKSCAN4 and NKAPL genes.…”