Genetic Copy Number Variations can Forecast Risk for Some Psychiatric Disorders


Copy number variations were broadly associated with an increased risk of autism spectrum disorder and ADHD.

For some psychiatric disorders, genetic copy number variations (CNV) can help predict risk, while for others are more narrow forecasts.

A team, led by Xabier Calle Sanchez, MS, 1Institute of Biological Psychiatry, Mental Health Services, Copenhagen University Hospital, produced an unbiased, population-based estimate of the prevalence, disease risks and trajectories, fertility, and mortality of genetic copy number variants implicated in neuropsychiatric disorders.

A Lack of Research

There remains a dearth in unbiased, population-based estimates on the prevalence, disease risks and trajectories, fertility, and mortality involving several recurrent genomic copy number variants and the link to mental disorders that contract chromosomal abnormalities and advanced precision health care.

In the population-based case-cohort study, the investigators identified individuals born between May 1, 1981 and December 31, 2015 from the Lundbeck Foundation Initiative for Integrative Psychiatric Research (iPYSCH) 2012 database. Overall, 57,377 individuals with attention deficit/hyperactivity disorder (ADHD), major depressive disorder (MDD), schizophrenia, autism spectrum disorder (ASD), or bipolar disorder were included in the final analysis. Also included in the analysis was 30,000 randomly drawn individuals from the database as a control group.

Patients were between 1-32 years during follow-up.

The investigators sought main outcomes of population-unbiased hazard ratios and survival estimates of CNV associations with the 5 ascertained psychiatric disorders, epilepsy, intellectual disability, selected somatic disorders, fertility, and mortality.

“Comparison with previous studies suggests that the lower risk estimates are associated with a higher CNV prevalence in the general population than in control samples of most case-control studies,” the authors wrote.

Associations with Psychiatric Disorders

Overall, copy number variants were broadly associated with an increased risk for ASD and ADHD. However, risk estimates for schizophrenia for most genetic copy number variants were lower than what was previously reported.

For the 1q21.1 deletion, there was a significant risk found for MDD (HR, 5.8; 95% CI, 1.5-22.2) and sex-specific risk of bipolar disorder (HR, 17; 95% CI, 1.5-189.3 for men only).

While both 1q21.1 and 15q13.3 were linked to increased risks for most of the diagnoses, the 17p12 deletion consistently resulted in less of a risk for psychiatric disorders (HR, 0.4-0.8). However, none of the estimates differed significantly from the general population.

After conducting a trajectory analysis, the investigators found while diagnostic risk profiles differed across loci, they were similar for deletions and duplications within each locus and sex-stratified analyses suggest pathogenicity of many genetic copy number variants could be modulated by sex.

“The findings of this study suggest that the iPSYCH population case cohort reveals broad disease risk for some of the studied CNVs and narrower risk for others, in addition to sex differential liability,” the authors wrote. “This finding on genomic risk variants at the level of a population may be important for health care planning and clinical decision making, and thus the advancement of precision health care.”

The study, “Comparing Copy Number Variations in a Danish Case Cohort of Individuals With Psychiatric Disorders,” was published online in JAMA Psychiatry.

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