Phenotypic association analyses with copy number variation in recurrent depressive disorder

James J.H. Rucker; Katherine E. Tansey; Margarita Rivera; Dalila Pinto; Sarah Cohen-Woods; Rudolf Uher; Katherine J. Aitchison; Nick Craddock; Michael J. Owen; Lisa Jones; Ian Jones; Ania Korszun; Michael R. Barnes; Martin Preisig; Ole Mors; Wolfgang Maier; John Rice; Marcella Rietschel; Florian Holsboer; Anne E. Farmer; Ian W. Craig; Stephen W. Scherer; Peter McGuffin; Gerome Breen

doi:10.1016/j.biopsych.2015.02.025

Phenotypic association analyses with copy number variation in recurrent depressive disorder

James J.H. Rucker, Katherine E. Tansey, Margarita Rivera, Dalila Pinto, Sarah Cohen-Woods, Rudolf Uher, Katherine J. Aitchison, Nick Craddock, Michael J. Owen, Lisa Jones, Ian Jones, Ania Korszun, Michael R. Barnes, Martin Preisig, Ole Mors, Wolfgang Maier, John Rice, Marcella Rietschel, Florian Holsboer, Anne E. FarmerIan W. Craig, Stephen W. Scherer, Peter McGuffin, Gerome Breen

Medicine

Medicine

Producción científica: Contribución a una revista › Artículo › revisión exhaustiva

18 Citas (Scopus)

Resumen

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.

Idioma original	English
Páginas (desde-hasta)	329-336
Número de páginas	8
Publicación	Biological Psychiatry
Volumen	79
N.º	4
DOI	https://doi.org/10.1016/j.biopsych.2015.02.025
Estado	Published - feb. 15 2016

Nota bibliográfica

Funding Information:
This work was supported by a joint grant from the United Kingdom Medical Research Council and GlaxoSmithKline (Grant No. G0701420) and the National Institute for Health Research (NIHR) Biomedical Research Centre for Mental Health at South London and Maudsley National Health Service (NHS) Foundation Trust and Institute of Psychiatry, King’s College London. This work presents independent research in part funded by the NIHR. The views expressed are those of the authors and not necessarily those of the NHS, the NIHR, or the Department of Health. This work was also supported by the Wellcome Trust Grant No. 086635 (JJHR); NIHR Specialist Biomedical Research Centre for Mental Health at the South London and Maudsley NHS Foundation Trust and the Institute of Psychiatry, King’s College London (SC-W); a Marie Curie Intra-European Fellowship within the 7th European Community Framework Programme (MRiv); European Commission Grant Agreement No. 115008 (RU, PM); and Canada Research Chairs program ( http://www.chairs-chaires.gc.ca/ ) (RU). Dr. Aitchison holds an Alberta Centennial Addiction and Mental Health Research Chair, funded by the government of Alberta, Canada. The Genome Based Therapeutic Drugs for Depression study was funded by a European Commission Framework 6 grant, European Commission Contract Reference LSHB-CT-2003-503428, and GlaxoSmithKline.

Publisher Copyright:
© 2016 Society of Biological Psychiatry.

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Biological Psychiatry

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10.1016/j.biopsych.2015.02.025

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Rucker, J. J. H., Tansey, K. E., Rivera, M., Pinto, D., Cohen-Woods, S., Uher, R., Aitchison, K. J., Craddock, N., Owen, M. J., Jones, L., Jones, I., Korszun, A., Barnes, M. R., Preisig, M., Mors, O., Maier, W., Rice, J., Rietschel, M., Holsboer, F., ... Breen, G. (2016). Phenotypic association analyses with copy number variation in recurrent depressive disorder. Biological Psychiatry, 79(4), 329-336. https://doi.org/10.1016/j.biopsych.2015.02.025

Rucker, JJH, Tansey, KE, Rivera, M, Pinto, D, Cohen-Woods, S, Uher, R, Aitchison, KJ, Craddock, N, Owen, MJ, Jones, L, Jones, I, Korszun, A, Barnes, MR, Preisig, M, Mors, O, Maier, W, Rice, J, Rietschel, M, Holsboer, F, Farmer, AE, Craig, IW, Scherer, SW, McGuffin, P & Breen, G 2016, 'Phenotypic association analyses with copy number variation in recurrent depressive disorder', Biological Psychiatry, vol. 79, n.º 4, pp. 329-336. https://doi.org/10.1016/j.biopsych.2015.02.025

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title = "Phenotypic association analyses with copy number variation in recurrent depressive disorder",

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.",

author = "Rucker, {James J.H.} and Tansey, {Katherine E.} and Margarita Rivera and Dalila Pinto and Sarah Cohen-Woods and Rudolf Uher and Aitchison, {Katherine J.} and Nick Craddock and Owen, {Michael J.} and Lisa Jones and Ian Jones and Ania Korszun and Barnes, {Michael R.} and Martin Preisig and Ole Mors and Wolfgang Maier and John Rice and Marcella Rietschel and Florian Holsboer and Farmer, {Anne E.} and Craig, {Ian W.} and Scherer, {Stephen W.} and Peter McGuffin and Gerome Breen",

note = "Funding Information: This work was supported by a joint grant from the United Kingdom Medical Research Council and GlaxoSmithKline (Grant No. G0701420) and the National Institute for Health Research (NIHR) Biomedical Research Centre for Mental Health at South London and Maudsley National Health Service (NHS) Foundation Trust and Institute of Psychiatry, King{\textquoteright}s College London. This work presents independent research in part funded by the NIHR. The views expressed are those of the authors and not necessarily those of the NHS, the NIHR, or the Department of Health. This work was also supported by the Wellcome Trust Grant No. 086635 (JJHR); NIHR Specialist Biomedical Research Centre for Mental Health at the South London and Maudsley NHS Foundation Trust and the Institute of Psychiatry, King{\textquoteright}s College London (SC-W); a Marie Curie Intra-European Fellowship within the 7th European Community Framework Programme (MRiv); European Commission Grant Agreement No. 115008 (RU, PM); and Canada Research Chairs program ( http://www.chairs-chaires.gc.ca/ ) (RU). Dr. Aitchison holds an Alberta Centennial Addiction and Mental Health Research Chair, funded by the government of Alberta, Canada. The Genome Based Therapeutic Drugs for Depression study was funded by a European Commission Framework 6 grant, European Commission Contract Reference LSHB-CT-2003-503428, and GlaxoSmithKline. Publisher Copyright: {\textcopyright} 2016 Society of Biological Psychiatry.",

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doi = "10.1016/j.biopsych.2015.02.025",

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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 - Funding Information: This work was supported by a joint grant from the United Kingdom Medical Research Council and GlaxoSmithKline (Grant No. G0701420) and the National Institute for Health Research (NIHR) Biomedical Research Centre for Mental Health at South London and Maudsley National Health Service (NHS) Foundation Trust and Institute of Psychiatry, King’s College London. This work presents independent research in part funded by the NIHR. The views expressed are those of the authors and not necessarily those of the NHS, the NIHR, or the Department of Health. This work was also supported by the Wellcome Trust Grant No. 086635 (JJHR); NIHR Specialist Biomedical Research Centre for Mental Health at the South London and Maudsley NHS Foundation Trust and the Institute of Psychiatry, King’s College London (SC-W); a Marie Curie Intra-European Fellowship within the 7th European Community Framework Programme (MRiv); European Commission Grant Agreement No. 115008 (RU, PM); and Canada Research Chairs program ( http://www.chairs-chaires.gc.ca/ ) (RU). Dr. Aitchison holds an Alberta Centennial Addiction and Mental Health Research Chair, funded by the government of Alberta, Canada. The Genome Based Therapeutic Drugs for Depression study was funded by a European Commission Framework 6 grant, European Commission Contract Reference LSHB-CT-2003-503428, and GlaxoSmithKline. 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.

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Phenotypic association analyses with copy number variation in recurrent depressive disorder

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