Abstract
Background
Our understanding of the impact of copy number variants (CNVs) on psychopathology
and their joint influence with polygenic risk scores (PRSs) remains limited.
Methods
The UK Biobank recruited 502,534 individuals ages 37 to 73 years living in the United
Kingdom between 2006 and 2010. After quality control, genotype data from 459,855 individuals
were available for CNV calling. A total of 61 commonly studied recurrent neuropsychiatric
CNVs were selected for analyses and examined individually and in aggregate (any CNV,
deletion, or duplication). CNV risk scores were used to quantify intolerance of CNVs
to haploinsufficiency. Major depressive disorder and generalized anxiety disorder
PRSs were generated for White British individuals (N = 408,870). Mood/anxiety factor scores were generated using item-level questionnaire
data (N = 501,289).
Results
CNV carriers showed higher mood/anxiety scores than noncarriers, with the largest
effects seen for intolerant deletions. A total of 11 individual deletions and 8 duplications
were associated with higher mood/anxiety. Carriers of the 9p24.3 (DMRT1) duplication showed lower mood/anxiety. Associations remained significant for most
CNVs when excluding individuals with psychiatric diagnoses. Nominally significant
CNV × PRS interactions provided preliminary evidence that associations between select
individual CNVs, but not CNVs in aggregate, and mood/anxiety may be modulated by PRSs.
Conclusions
CNVs associated with risk for psychiatric disorders showed small to large effects
on dimensional mood/anxiety scores in a general population cohort, even when excluding
individuals with psychiatric diagnoses. CNV × PRS interactions showed that associations
between select CNVs and mood/anxiety may be modulated by PRSs.
Keywords
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Article info
Publication history
Published online: February 08, 2023
Accepted:
January 31,
2023
Received in revised form:
January 31,
2023
Received:
July 6,
2022
Publication stage
In Press Journal Pre-ProofIdentification
Copyright
© 2023 Society of Biological Psychiatry.
