Identification of novel schizophrenia loci by homozygosity mapping using DNA microarray analysis (CBX141). unidentified

The recent development of high-resolution DNA microarrays, in which hundreds of thousands of SNPs are genotyped, enables the rapid identification of susceptibility genes for complex diseases. Clusters of these SNPs may show runs of homozygosity (ROH) that can be analyzed for association with disease. An analysis of patients whose parents were first cousins enables the search of autozygous segments in their offspring. Here, using the Affymetrix? Genome-Wide Human SNP Array 5.0 to determine ROHs, we genotyped nine individuals with schizophrenia whose parents were first cousins. We identified overlapping ROHs on chromosomes 1, 4, 5, 6, 7, 8, 10, 11, 12, 13, 16, 17, 19, 20, and 21 in four individuals. Only the locus in chromosome 5 has been reported previously. The ROHs at chromosome 5q23.3-q31.1 include the candidate genes HINT1, SPEC2, PDZ-GEF2, and ACSL6. When rare variants including copy number variation account for phenotype, homozygosity mapping using DNA microarray technology is extremely powerful, robust, rapid, and cost-effective for uncovering the responsible loci for complex disorders, including psychiatric diseases. This study suggests that there might be pathogenic recessive variants for schizophrenia that have not been detected in previous studies. Analysis of patients whose parents are first cousins may provide new insights for genetic research of psychiatric diseases.