Accumulation of minor alleles and risk prediction in schizophrenia

Schizophrenia is a common neuropsychiatric disorder with a lifetime risk of 1%. Accumulation of common polygenic variations has been found to be an important risk factor. Recent studies showed a role for the enrichment of minor alleles (MAs) of SNPs in complex diseases such as Parkinson’s disease. Here we similarly studied the role of genome wide MAs in schizophrenia using public datasets. Relative to matched controls, schizophrenia cases showed higher average values in minor allele content (MAC) or the average amount of MAs per subject. By risk prediction analysis based on weighted genetic risk score (wGRS) of MAs, we identified an optimal MA set consisting of 23 238 variants that could be used to predict 3.14% of schizophrenia cases, which is comparable to using 22q11 deletion to detect schizophrenia cases. Pathway enrichment analysis of these SNPs identified 30 pathways with false discovery rate (FDR) <0.02 and of significant P-value, most of which are known to be linked with schizophrenia and other neurological disorders. These results suggest that MAs accumulation may be a risk factor to schizophrenia and provide a method to genetically screen for this disease.