Phenotypic Association Analyses With Copy Number Variation in Recurrent Depressive Disorder

Area of Science:

• Genetics
• Psychiatry
• Molecular Biology

Background:

• Identifying the genetic underpinnings of depressive disorders remains a significant challenge.
• Previous research linked rare exonic deletion copy number variants (CNVs) to recurrent depressive disorder (RDD).
• Sex chromosome abnormalities have also been noted in association with RDD.

Purpose of the Study:

• To re-examine a dataset of recurrent depressive disorder (RDD) cases and controls.
• To investigate the role of larger CNVs and chromosomal abnormalities in RDD.
• To perform association analyses with clinical data.

Main Methods:

• Reanalysis of an RDD dataset comprising 3106 cases and 459 screened controls, plus 2699 population controls.
• Investigation of larger CNVs and chromosomal abnormalities.
• Association analyses with clinical data.

Main Results:

• An enrichment of Turner's syndrome was observed in RDD cases compared to a large infant population sample (p = .023, OR = 7.76).
• A case of diploid/triploid mosaicism and several cases of uniparental isodisomy were identified.
• Large deletion CNVs were not more frequent in cases than controls, but contained more genes in cases (p = .0002).

Conclusions:

• The study does not support a substantial role for CNVs in RDD after statistical correction.
• Occasional RDD cases may harbor large, etiological variants.
• Genetic pleiotropy and sample heterogeneity necessitate very large sample sizes for conclusive genetic studies in mood disorders.