Less than1% of the global population suffers from Schizophrenia, a potentially debilitating disease in which the patient loses the ability to distinguish between reality and fantasy. Schizophrenia usually manifests during adolescence, and brings with it a heavy financial and emotional burden for close family and friends. Previous research on twins has established that genetic factors are associated with schizophrenia, but the so far scientists have been unable to identify precisely how these factors confer risk.

LUO Xiongjian’s research group examined whether expression-associated genetic variants contributed to schizophrenia susceptibility by integrating genome-associated data on schizophrenia and brain-expression quantitative-trait loci using a statistical framework called “Sherlock.” This analysis associated one gene with schizophrenia: ZNF323. In order to further study the effects of this gene, LUO Xiongjian reached out to his international counterparts to conduct large-scale correlation research, which further bolstered their findings. One single nucleotide polymorphism (rs1150711 SNP) associated with ZNF323 expression was found to be significantly associated with schizophrenia (P=6.85 * 10-10).  

Further study showed that the allele (rs1150711-T) associated with the low expression of ZNF323 was significantly enriched in schizophrenic patients. Consistent with the results of other genetic studies, in patients with schizophrenia ZNF323 was down-regulated in the hippocampal and frontal-cortex regions of the brain. Therefore, rs1150711 is likely to confer a risk for schizophrenia, but the T allele of this polymorphism was also found to have a positive effect on lung function. rs1150711 is likely to affect the expression of ZNF323 and therefore confer susceptibility to schizophrenia and also affect lung function. This gene may therefore have been positively selected over the course of human evolution, once again illustrating that evolution can be a double-edged sword: people may be able to breathe better, but then again, they may also get schizophrenia.

The full article “Systematic integration of brain eQTL and GWAS identifies ZNF323 as a novel schizophrenia risk gene and suggests recent positive selection based on compensatory advantage on pulmonary function” was published in the Schizophrenia Bulletin, available online at: http://schizophreniabulletin.oxfordjournals.org/content/early/2015/03/10/schbul.sbv017.abstract