| Abstract |
There is genetic evidence that精神分裂症is a polygenic disorder with a large number of loci of small effect on disease susceptibility. Genome-wide association studies (GWASs) of精神分裂症have had limited success, with the best finding at the MHC locus at chromosome 6p. A recent effort of the Psychiatric GWAS consortium (PGC) yielded five novel loci for精神分裂症. In this study, we aim to highlight additional精神分裂症susceptibility loci from the PGC study by combining the top association findings from the discovery stage (9394精神分裂症cases and 12?462 controls) with expression QTLs (eQTLs) and differential gene expression in whole blood of精神分裂症patients and controls. We examined the 6192 single-nucleotide polymorphisms (SNPs) with significance threshold at P<0.001. eQTLs were calculated for these SNPs in a sample of healthy controls (n=437). The transcripts significantly regulated by the top SNPs from the GWAS meta-analysis were subsequently tested for differential expression in an independent set of精神分裂症cases and controls (n=202). After correction for multiple testing, the eQTL analysis yielded 40 significant cis-acting effects of the SNPs. Seven of these transcripts show differential expression between cases and controls. Of these, the effect of three genes (RNF5, TRIM26 and HLA-DRB3) coincided with the direction expected from meta-analysis findings and were all located within the MHC region. Our results identify new genes of interest and highlight again the involvement of the MHC region in精神分裂症susceptibility. |