Official websites use. Share sensitive information only on official, secure websites. Analyses: C. Data collection: C. B collected and provided the data for the UCLA cohort. Overall, little is known about how different CNVs conferring risk for the same condition may affect subcortical brain structures and how these alterations relate to the level of disease risk conferred by CNVs.
To fill this gap, we investigated gross volume, and vertex level thickness, and surface maps of subcortical structures in 11 CNVs and 6 NPDs. All CNVs showed alterations in at least one subcortical measure. Each structure was affected by at least two CNVs, and the hippocampus and amygdala were affected by five.
Shape analyses detected subregional alterations that were averaged out in volume analyses. Effect sizes of CNVs on subcortical volume, thickness, and local-surface-area were correlated with their previously reported effect sizes on cognition and risk for ASD and SZ. Our findings demonstrate that subcortical alterations associated with CNVs show varying levels of similarities with those associated with neuropsychiatric conditions.
Subcortical brain structures play a critical role in cognitive, affective, and social functions in humans 1 , 2. Large-scale international neuroimaging studies have shown that major neurodevelopmental and psychiatric disorders NPDs 3 , including schizophrenia SZ 4 , major-depressive-disorder MDD 5 , bipolar disorder BD 6 , obsessive-compulsive-disorder OCD 7 , autism-spectrum-disorder ASD 8 , and attention-deficit-hyperactivity-disorder ADHD 9 are associated with alterations in subcortical structures 10 — These case-control association studies have revealed small to moderate effect sizes on brain morphometry which have been interpreted as a consequence of heterogeneity at the level of genetics and brain mechanisms 13 — There is a growing body of literature demonstrating subcortical volumetric alterations associated with genetic risk for NPDs as conferred by copy number variants CNVs.
Among the CNVs included in this study, the largest increases in risk for SZ have been documented for the 22q ASD risk is highest for 16p All CNVs affect the cognitive ability to a varying degree decrease between 2. CNV chromosomal coordinates are provided in megabase Mb with the number of genes encompassed in each CNV and a well-known gene for each locus, to help recognize the CNV. Clinically ascertained participants come from five cohorts and non-clinically ascertained participants are from the UK Biobank.
