Genomic Variants Contribute to Cognitive Impairment

Genetic alterations of rare deletions or duplications of small DNA segments, called copy number variants (CNVs), have been known to increase risk of neurodevelopmental disorders such as schizophrenia, autism spectrum disorder, and intellectual disability.

The largest analysis to date on the effects of CNVs on cognition in a general population has been carried out, while most previous studies have focused on disease populations. The findings should help health professionals understand the effects of neurodevelopmental genetic abnormalities, even when they do not lead to the emergence of a disease.

Scientists at Cardiff University School of Medicine (Cardiff, UK) analyzed data from the UK Biobank, a repository of extensive demographic, health, and cognitive data from 500,000 adults. The first nearly 152,000 of those have also been genotyped and were included in the study. The team focused on CNVs that have been statistically linked with risk of neurodevelopmental disorders (neurodevelopmental CNVs), including 12 schizophrenia-associated CNVs and a group of 41 CNVs associated with other disorders.

The scientists used Affymetrix Power Tools and PennCNV-Affy software to analyze Affymetrix microarrays of the first 152,728 genotyped individuals. They annotated a list of 93 CNVs and compared their frequencies with control datasets and analyzed the performance on seven cognitive tests of 1,087carriers of 12 CNVs associated with schizophrenia and of 484 carriers of another 41 neurodevelopmental CNVs.

In a comparison of performance on cognitive tests between adults with schizophrenia, carriers of neurodevelopmental CNVs who were otherwise healthy, and people who did not carry any CNVs in their genome (noncarriers), those with schizophrenia performed the worst. Performance of carriers fell in between noncarriers and people with schizophrenia. Carriers also had lower educational attainment and tended to have occupations requiring less skill or training. No differences were found between carriers of the 12 schizophrenia-associated CNVs versus carriers of the other neurodevelopmental CNVs.

George Kirov, MD, PhD, a professor and senior author of the study said, “The cognitive performance of carriers of schizophrenia-associated CNVs was indeed reduced, but the differences were subtle and a large proportion of CNV carriers appeared to function very well. Many CNV carriers reached very high levels of academic achievement, and successfully obtain highly skilled or cognitively demanding occupations.” The study was published on July 15, 2017, in the journal Biological Psychiatry.

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Cardiff University School of Medicine