Whole exome sequencing of schizophrenia patients with high level of autozygosity.

Despite an estimated heritability up to 80% the genetic architecture of schizophrenia (SZ) remains unclear. Only about 32% of the genetic variability of schizophrenia has been attributed to common susceptibility alleles, this implying that other genetic factors are involved, as demonstrated by the identification of rare copy number variants (CNV) in some patients. At present, no exhaustive data on the contribution of rare recessive variants have been reported. Recessive variants are expected to have a major impact on inbreed subjects. Therefore, by autozygosity mapping we selected from a cohort of 180 patients those with high levels of autozygosity and submitted these 7 patients to whole exome sequencing (WES) analysis. Prioritization of the identified variants evidenced in the autozygous regions of these patients some variants representing good candidate mutations in SZ, since predicted as damaging and/or mapping in genes expressed in brain or previously associated to SZ. Our results, therefore, suggest that recessive variants might be involved in SZ , at least in those patients with high levels of autozygosity.