Cargando…

Resequencing Three Candidate Genes for Major Depressive Disorder in a Dutch Cohort

Major depressive disorder (MDD) is a psychiatric disorder, characterized by periods of low mood of more than two weeks, loss of interest in normally enjoyable activities and behavioral changes. MDD is a complex disorder and does not have a single genetic cause. In 2009 a genome wide association stud...

Descripción completa

Detalles Bibliográficos
Autores principales: Verbeek, Eva C., Bevova, Marianna R., Bochdanovits, Zoltán, Rizzu, Patrizia, Bakker, Ingrid M. C., Uithuisje, Tiny, De Geus, Eco J., Smit, Johannes H., Penninx, Brenda W., Boomsma, Dorret I., Hoogendijk, Witte J. G., Heutink, Peter
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2013
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3836783/
https://www.ncbi.nlm.nih.gov/pubmed/24278217
http://dx.doi.org/10.1371/journal.pone.0079921
_version_ 1782292349185949696
author Verbeek, Eva C.
Bevova, Marianna R.
Bochdanovits, Zoltán
Rizzu, Patrizia
Bakker, Ingrid M. C.
Uithuisje, Tiny
De Geus, Eco J.
Smit, Johannes H.
Penninx, Brenda W.
Boomsma, Dorret I.
Hoogendijk, Witte J. G.
Heutink, Peter
author_facet Verbeek, Eva C.
Bevova, Marianna R.
Bochdanovits, Zoltán
Rizzu, Patrizia
Bakker, Ingrid M. C.
Uithuisje, Tiny
De Geus, Eco J.
Smit, Johannes H.
Penninx, Brenda W.
Boomsma, Dorret I.
Hoogendijk, Witte J. G.
Heutink, Peter
author_sort Verbeek, Eva C.
collection PubMed
description Major depressive disorder (MDD) is a psychiatric disorder, characterized by periods of low mood of more than two weeks, loss of interest in normally enjoyable activities and behavioral changes. MDD is a complex disorder and does not have a single genetic cause. In 2009 a genome wide association study (GWAS) was performed on the Dutch GAIN-MDD cohort. Many of the top signals of this GWAS mapped to a region spanning the gene PCLO, and the non-synonymous coding single nucleotide polymorphism (SNP) rs2522833 in the PCLO gene became genome wide significant after post-hoc analysis. We performed resequencing of PCLO, GRM7, and SLC6A4 in 50 control samples from the GAIN-MDD cohort, to detect new genomic variants. Subsequently, we genotyped these variants in the entire GAIN-MDD cohort and performed association analysis to investigate if rs2522833 is the causal variant or simply in linkage disequilibrium with a more associated variant. GRM7 and SLC6A4 are both candidate genes for MDD from literature. We aimed to gather more evidence that rs2522833 is indeed the causal variant in the GAIN-MDD cohort or to find a previously undetected common variant in either PCLO, GRM7, or SLC6A4 with a higher association in this cohort. After next generation sequencing and association analysis we excluded the possibility of an undetected common variant to be more associated. For neither PCLO nor GRM7 we found a more associated variant. For SLC6A4, we found a new SNP that showed a lower P-value (P = 0.07) than in the GAIN-MDD GWAS (P = 0.09). However, no evidence for genome-wide significance was found. Although we did not take into account rare variants, we conclude that our results provide further support for the hypothesis that the non-synonymous coding SNP rs2522833 in the PCLO gene is indeed likely to be the causal variant in the GAIN-MDD cohort.
format Online
Article
Text
id pubmed-3836783
institution National Center for Biotechnology Information
language English
publishDate 2013
publisher Public Library of Science
record_format MEDLINE/PubMed
spelling pubmed-38367832013-11-25 Resequencing Three Candidate Genes for Major Depressive Disorder in a Dutch Cohort Verbeek, Eva C. Bevova, Marianna R. Bochdanovits, Zoltán Rizzu, Patrizia Bakker, Ingrid M. C. Uithuisje, Tiny De Geus, Eco J. Smit, Johannes H. Penninx, Brenda W. Boomsma, Dorret I. Hoogendijk, Witte J. G. Heutink, Peter PLoS One Research Article Major depressive disorder (MDD) is a psychiatric disorder, characterized by periods of low mood of more than two weeks, loss of interest in normally enjoyable activities and behavioral changes. MDD is a complex disorder and does not have a single genetic cause. In 2009 a genome wide association study (GWAS) was performed on the Dutch GAIN-MDD cohort. Many of the top signals of this GWAS mapped to a region spanning the gene PCLO, and the non-synonymous coding single nucleotide polymorphism (SNP) rs2522833 in the PCLO gene became genome wide significant after post-hoc analysis. We performed resequencing of PCLO, GRM7, and SLC6A4 in 50 control samples from the GAIN-MDD cohort, to detect new genomic variants. Subsequently, we genotyped these variants in the entire GAIN-MDD cohort and performed association analysis to investigate if rs2522833 is the causal variant or simply in linkage disequilibrium with a more associated variant. GRM7 and SLC6A4 are both candidate genes for MDD from literature. We aimed to gather more evidence that rs2522833 is indeed the causal variant in the GAIN-MDD cohort or to find a previously undetected common variant in either PCLO, GRM7, or SLC6A4 with a higher association in this cohort. After next generation sequencing and association analysis we excluded the possibility of an undetected common variant to be more associated. For neither PCLO nor GRM7 we found a more associated variant. For SLC6A4, we found a new SNP that showed a lower P-value (P = 0.07) than in the GAIN-MDD GWAS (P = 0.09). However, no evidence for genome-wide significance was found. Although we did not take into account rare variants, we conclude that our results provide further support for the hypothesis that the non-synonymous coding SNP rs2522833 in the PCLO gene is indeed likely to be the causal variant in the GAIN-MDD cohort. Public Library of Science 2013-11-21 /pmc/articles/PMC3836783/ /pubmed/24278217 http://dx.doi.org/10.1371/journal.pone.0079921 Text en © 2013 Verbeek et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Verbeek, Eva C.
Bevova, Marianna R.
Bochdanovits, Zoltán
Rizzu, Patrizia
Bakker, Ingrid M. C.
Uithuisje, Tiny
De Geus, Eco J.
Smit, Johannes H.
Penninx, Brenda W.
Boomsma, Dorret I.
Hoogendijk, Witte J. G.
Heutink, Peter
Resequencing Three Candidate Genes for Major Depressive Disorder in a Dutch Cohort
title Resequencing Three Candidate Genes for Major Depressive Disorder in a Dutch Cohort
title_full Resequencing Three Candidate Genes for Major Depressive Disorder in a Dutch Cohort
title_fullStr Resequencing Three Candidate Genes for Major Depressive Disorder in a Dutch Cohort
title_full_unstemmed Resequencing Three Candidate Genes for Major Depressive Disorder in a Dutch Cohort
title_short Resequencing Three Candidate Genes for Major Depressive Disorder in a Dutch Cohort
title_sort resequencing three candidate genes for major depressive disorder in a dutch cohort
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3836783/
https://www.ncbi.nlm.nih.gov/pubmed/24278217
http://dx.doi.org/10.1371/journal.pone.0079921
work_keys_str_mv AT verbeekevac resequencingthreecandidategenesformajordepressivedisorderinadutchcohort
AT bevovamariannar resequencingthreecandidategenesformajordepressivedisorderinadutchcohort
AT bochdanovitszoltan resequencingthreecandidategenesformajordepressivedisorderinadutchcohort
AT rizzupatrizia resequencingthreecandidategenesformajordepressivedisorderinadutchcohort
AT bakkeringridmc resequencingthreecandidategenesformajordepressivedisorderinadutchcohort
AT uithuisjetiny resequencingthreecandidategenesformajordepressivedisorderinadutchcohort
AT degeusecoj resequencingthreecandidategenesformajordepressivedisorderinadutchcohort
AT smitjohannesh resequencingthreecandidategenesformajordepressivedisorderinadutchcohort
AT penninxbrendaw resequencingthreecandidategenesformajordepressivedisorderinadutchcohort
AT boomsmadorreti resequencingthreecandidategenesformajordepressivedisorderinadutchcohort
AT hoogendijkwittejg resequencingthreecandidategenesformajordepressivedisorderinadutchcohort
AT heutinkpeter resequencingthreecandidategenesformajordepressivedisorderinadutchcohort