de novo copy number variations in schizophrenia

Abstract

Introduction: Reduced fecundity, associated with disorders such as autism, schizophrenia and mental retardation, places negative selection pressure on haplotypes carrying risk alleles. The genetic risk of diseases under such pressure is less likely to be accounted for by common, low penetrant variants, explaining in part the limited success in genome-wide association studies for these disorders. Recurrent micro-deletions and duplications, found in excess in these disorders, may account for a proportion of the genetic risk.

Methods: Unlike single nucleotide polymorphisms (SNPs) with very low minor allele frequency, rare copy number variations (CNVs) can be uncovered using available microarrays for genome-wide association analysis. In a cohort of parent-offspring trio(Trio) we have identified de novo CNVs and tested those variants for enrichment among patients with schizophrenia.

Results: It is known that CNVs confer risk of schizophrenia and those variants can either be de novo transmitted. We have identified 5 de novo CNVs in patients with schizophrenia (n=133), compared with non-psychiatric subjects having (n=515) 6 de novo CNVs, we find an excess of de novo CNV among patients with schizophrenia.