Copy number variations and cognitive phenotypes in unselected populations

Area of Science:

• Human Genetics
• Population Genomics
• Neurodevelopmental Disorders

Background:

• The role of copy number variations (CNVs) in intellectual disability is primarily studied in clinical cohorts.
• The impact of CNVs on cognitive phenotypes in the general population remains largely unknown.
• CNVs are genomic alterations involving differing numbers of copies of genetic sequences.

Purpose of the Study:

• To investigate clinical features of CNVs associated with known syndromes in unselected adults.
• To assess the genome-wide impact of rare CNVs on educational attainment and intellectual disability prevalence in the general population.

Main Methods:

• Analysis of CNVs in a large population biobank (n=7877) from Estonia.
• Genotype-phenotype association studies for educational attainment and intellectual disability.
• Replication of findings in independent cohorts from the UK, US, and Italy.

Main Results:

• CNV carriers in the general population exhibited phenotypes similar to clinically ascertained individuals.
• Rare CNVs (≥250 kb) were significantly associated with increased prevalence of intellectual disability.
• CNV carriers showed significantly lower educational attainment, with higher rates of not graduating high school.

Conclusions:

• Pathogenic CNVs in seemingly healthy adults can be associated with unrecognized clinical sequelae.
• Rare CNVs are negatively associated with educational attainment, impacting public health and genomics research.
• Further replication in diverse populations is crucial for understanding the implications of these findings.