hide
Free keywords:
Affective disorders, copy number variation, depression, genetics, phenotypes
Abstract:
BACKGROUND: Defining the molecular genomic basis of the likelihood of
developing depressive disorder is a considerable challenge. We
previously associated rare, exonic deletion copy number variants (CNV)
with recurrent depressive disorder (RDD). Sex chromosome abnormalities
also have been observed to co-occur with RDD.
METHODS: In this reanalysis of our RDD dataset (N = 3106 cases; 459
screened control samples and 2699 population control samples), we
further investigated the role of larger CNVs and chromosomal
abnormalities in RDD and performed association analyses with clinical
data derived from this dataset.
RESULTS: We found an enrichment of Turner's syndrome among cases of
depression compared with the frequency observed in a large population
sample (N = 34,910) of live-born infants collected in Denmark (two-sided
p =.023, odds ratio = 7.76 [95% confidence interval = 1.79-33.6]), a
case of diploid/triploid mosaicism, and several cases of uniparental
isodisomy. In contrast to our previous analysis, large deletion CNVs
were no more frequent in cases than control samples, although deletion
CNVs in cases contained more genes than control samples (two-sided p
=.0002).
CONCLUSIONS: After statistical correction for multiple comparisons, our
data do not support a substantial role for CNVs in RDD, although (as has
been observed in similar samples) occasional cases may harbor large
variants with etiological significance. Genetic pleiotropy and sample
heterogeneity suggest that very large sample sizes are required to study
conclusively the role of genetic variation in mood disorders.
