It is known that de novo microdeletions play a role in the susceptibility of neuropsychiatric traits such as schizophrenia and autism. However, the majority of the genomic variation (including microdeletions) is inherited and does not represent de novo events. Evidence from large studies, however, points to a higher incidence of rare genomic deletions in patients, while we know that the same variants may also be present in unaffected subjects including relatives of patients. Our own findings suggest that there are cases in which large genomic deletions may uncover recessive, functional variants at the remaining allele. We hypothesize that the non-deleted alleles in schizophrenia patients may be enriched with variants affecting gene function compared to non-deleted alleles present in unaffected subjects. To explore this further, we will collect sequence data of coding regions of genes that are affected by genomic deletions in 250 schizophrenia cases and 250 unaffected controls for which copy number variation data is available.
Schizophrenia is a heritable disease but little is known about which genes play important roles in disease susceptibility. This study explores the rate of rare DNA mutations affecting gene function in patients versus unaffected individuals.
|Loohuis, Loes M Olde; Vorstman, Jacob A S; Ori, Anil P et al. (2015) Genome-wide burden of deleterious coding variants increased in schizophrenia. Nat Commun 6:7501|