Cross-Disorder Comparison of Four Neuropsychiatric CNV Loci

Abstract

Copy number variants (CNVs) have been identified as a major risk factor in neuropsychiatric disor-ders. In this review, we describe the phenotypes and syn-dromic features associated with CNVs at four of the best-characterized risk loci for these disorders: 15q11.2-13.1, 22q11.2, 16p11.2, and 7q11.23. By considering the repor-ted prevalence of these CNVs in autism, intellectual dis-ability, schizophrenia, and controls, we demonstrate a pattern of asymmetric shared risk in which CNVs increase the risk of multiple disorders but to differing degrees. This asymmetric risk sharing is incompatible with a model in which CNVs observed in autism or schizophrenia are secondary to a reduction in IQ, but favors a more complex relationship between individual CNVs and specific neuro-psychiatric phenotypes. Finally, we discuss how the lessons learned from CNVs in neuropsychiatric disorders will translate to the expanding list of genes being associated with these disorders through exome sequencing.