RT Journal Article
T1 Phenotypic Association Analyses With Copy Number Variation in Recurrent Depressive Disorder.
A1 Rucker, James J H
A1 Tansey, Katherine E
A1 Rivera, Margarita
A1 Pinto, Dalila
A1 Cohen-Woods, Sarah
A1 Uher, Rudolf
A1 Aitchison, Katherine J
A1 Craddock, Nick
A1 Owen, Michael J
A1 Jones, Lisa
A1 Jones, Ian
A1 Korszun, Ania
A1 Barnes, Michael R
A1 Preisig, Martin
A1 Mors, Ole
A1 Maier, Wolfgang
A1 Rice, John
A1 Rietschel, Marcella
A1 Holsboer, Florian
A1 Farmer, Anne E
A1 Craig, Ian W
A1 Scherer, Stephen W
A1 McGuffin, Peter
A1 Breen, Gerome
K1 Affective disorders
K1 Copy number variation
K1 Depression
K1 Genetics
K1 Phenotypes
AB 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. 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. 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). 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.
YR 2015
FD 2015-02-25
LK http://hdl.handle.net/10668/9739
UL http://hdl.handle.net/10668/9739
LA en
DS RISalud
RD Apr 7, 2025