Assessing the Effects of Rare Copy Number Variants on Psychiatric Symptoms and Cognitive Ability in 1M Individuals

Abstract

Rare Copy Number Variants (CNVs) have the highest relative risks among identified genetic variants contributing to mental illness. However, our understanding of the impact of CNVs on psychiatric symptomatology and neurocognitive ability is limited in at least three ways. First, the effects sizes of the vast majority of CNVs on neuropsychiatric phenotypes remain poorly understood. Prior studies concentrated on the most recurrent CNVs, leaving more than 90% of these variants undocumented. Second, for CNVs frequent enough to be studied individually, the full spectrum of phenotypic variation is unknown because ascertainment has been performed through neurodevelopmental and specialty clinics, which presumably represent the severe end of the phenotypic spectrum. Few studies have been conducted in unselected populations. Finally, many CNVs seem to impact the same neuropsychiatric domains, suggesting a poly/omnigenic model for psychiatric symptomatology and neurocognitive ability.