Accumulation of Minor Alleles of Common SNPs in Schizophrenia

Schizophrenia is a common neuropsychiatric disorder with a lifetime risk of 1%. A number of large scale genome wide association studies have identified numerous individual risk single nucleotide polymorphisms (SNPs) whose precise roles in schizophrenia remain unknown. Accumulation of many of these risk alleles has been found to be a more important risk factor. Consistently, recent studies showed a role for enrichment of minor alleles (MAs) in complex diseases. Here we studied the role of MAs in general in schizophrenia using public datasets. Relative to matched controls, schizophrenia cases showed higher minor allele content (MAC), especially for the sporadic cases. By linkage analysis, we identified 82 419 SNPs that could be used to predict 2.2% schizophrenia cases with 100% certainty. Pathway enrichment analysis of these SNPs identified 17 pathways, 15 of which are known to be linked with Schizophrenia with the remaining 2 associated with other mental disorders. These results suggest a role for a collective effect of MAs in schizophrenia and provide a method to genetically screen for schizophrenia.