TY - JOUR
T1 - Phenotypic association analyses with copy number variation in recurrent depressive disorder
AU - Rucker, James J.H.
AU - Tansey, Katherine E.
AU - Rivera, Margarita
AU - Pinto, Dalila
AU - Cohen-Woods, Sarah
AU - Uher, Rudolf
AU - Aitchison, Katherine J.
AU - Craddock, Nick
AU - Owen, Michael J.
AU - Jones, Lisa
AU - Jones, Ian
AU - Korszun, Ania
AU - Barnes, Michael R.
AU - Preisig, Martin
AU - Mors, Ole
AU - Maier, Wolfgang
AU - Rice, John
AU - Rietschel, Marcella
AU - Holsboer, Florian
AU - Farmer, Anne E.
AU - Craig, Ian W.
AU - Scherer, Stephen W.
AU - McGuffin, Peter
AU - Breen, Gerome
N1 - Publisher Copyright:
© 2016 Society of Biological Psychiatry.
PY - 2016/2/15
Y1 - 2016/2/15
N2 - 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.
AB - 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.
KW - Affective disorders
KW - Copy number variation
KW - Depression
KW - Genetics
KW - Phenotypes
UR - http://www.scopus.com/inward/record.url?scp=84955180285&partnerID=8YFLogxK
U2 - 10.1016/j.biopsych.2015.02.025
DO - 10.1016/j.biopsych.2015.02.025
M3 - Article
C2 - 25861698
AN - SCOPUS:84955180285
SN - 0006-3223
VL - 79
SP - 329
EP - 336
JO - Biological Psychiatry
JF - Biological Psychiatry
IS - 4
ER -