Genome-Wide Significance for PCLO as a Gene for Major Depressive Disorder

Hamdi Mbarek; Yuri Milaneschi; Jouke-Jan Hottenga; Lannie Ligthart; Eco J C de Geus; Erik A Ehli; Gonneke Willemsen; Gareth E Davies; Jan H Smit; Dorret I Boomsma; Brenda W J H Penninx

doi:10.1017/thg.2017.30

Genome-Wide Significance for PCLO as a Gene for Major Depressive Disorder

Hamdi Mbarek
, Yuri Milaneschi
, Jouke-Jan Hottenga
, Lannie Ligthart
, Eco J C de Geus
, Erik A Ehli
, Gonneke Willemsen
, Gareth E Davies
, Jan H Smit
, Dorret I Boomsma
, Brenda W J H Penninx

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Abstract

In 2009, the first genome-wide association study (GWAS) for major depressive disorder (MDD) highlighted an association with PCLO locus on chromosome 7, although not reaching genome-wide significance level. In the present study, we revisited the original GWAS after increasing the overall sample size and the number of interrogated SNPs. In an analysis comparing 1,942 cases with lifetime diagnosis of MDD and 4,565 controls, PCLO showed a genome-wide significant association with MDD at SNP (rs2715157, p = 2.91 × 10-8) and gene-based (p = 1.48 × 10-7) level. Our results confirm the potential role of the PCLO gene in MDD, which is worth further replication and functional studies.

Original language	English
Pages (from-to)	267-270
Number of pages	4
Journal	Twin Research and Human Genetics
Volume	20
Issue number	4
Early online date	25 May 2017
DOIs	https://doi.org/10.1017/thg.2017.30
Publication status	Published - Aug 2017

Funding

Netherland Twin Register and Netherlands Study of Depression and Anxiety (NESDA): Funding was obtained from the Netherlands Organization for Scientific Research (NWO) and MagW/ZonMW grants Middelgroot-911- 09-032, Spinozapremie 56-464-14192, Geestkracht program of the Netherlands Organization for Health Research and Development (ZonMW 10-000-1002), Center for Medical Systems Biology (CSMB, NOW Genomics), Genetic influences on stability and change in psychopathology from childhood to young adulthood (ZonMW 912-10-020), NBIC/BioAssist/RK(2008.024), Biobanking and Biomolecular Resources Research Infrastructure (BBMRI- NL, 184.021.007), VU University's Institute for Health and Care Research (EMGO+) and Neuroscience Campus Amsterdam (NCA); the European Science Council (ERC Advanced, 230374). Part of the genotyping and analyses were funded by the Genetic Association Information Network (GAIN) of the Foundation for the National Institutes of Health, Rutgers University Cell and DNA Repository (NIMH U24 MH068457-06), the Avera Institute for Human Genetics, Sioux Falls, South Dakota (USA) and the National Institutes of Health (NIH R01 HD042157-01A1, MH081802, Grand Opportunity grants 1RC2 MH089951 and 1RC2 MH089995).

Funders	Funder number
Avera Institute for Human Genetics
BBMRI	184.021.007
Biobanking and Biomolecular Resources Research Infrastructure
European Science Council
NBIC/BioAssist/RK	2008.024
Netherlands Organization for Health Research and Development	10-000-1002
Spinozapremie	56-464-14192
VU University's Institute for Health and Care Research
National Institutes of Health	1RC2 MH089995, MH081802, R01 HD042157-01A1
National Institute of Mental Health	U24 MH068457-06, RC2MH089951
European Research Council	230374
Nederlandse Organisatie voor Wetenschappelijk Onderzoek	Middelgroot-911- 09-032
Centre for Medical Systems Biology	ZonMW 912-10-020

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

SDG 3 Good Health and Well-being

Keywords

Journal Article

Cohort Studies

Netherlands Twin Register (NTR)

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10.1017/thg.2017.30

Genome-wide-significance-for-pclo-as-a-gene-for-major-depressive-disorderFinal published version, 378 KBLicence: Article 25fa Dutch Copyright Act

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title = "Genome-Wide Significance for PCLO as a Gene for Major Depressive Disorder",

abstract = "In 2009, the first genome-wide association study (GWAS) for major depressive disorder (MDD) highlighted an association with PCLO locus on chromosome 7, although not reaching genome-wide significance level. In the present study, we revisited the original GWAS after increasing the overall sample size and the number of interrogated SNPs. In an analysis comparing 1,942 cases with lifetime diagnosis of MDD and 4,565 controls, PCLO showed a genome-wide significant association with MDD at SNP (rs2715157, p = 2.91 × 10-8) and gene-based (p = 1.48 × 10-7) level. Our results confirm the potential role of the PCLO gene in MDD, which is worth further replication and functional studies.",

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T1 - Genome-Wide Significance for PCLO as a Gene for Major Depressive Disorder

AU - Mbarek, Hamdi

AU - Milaneschi, Yuri

AU - Hottenga, Jouke-Jan

AU - Ligthart, Lannie

AU - de Geus, Eco J C

AU - Ehli, Erik A

AU - Willemsen, Gonneke

AU - Davies, Gareth E

AU - Smit, Jan H

AU - Boomsma, Dorret I

AU - Penninx, Brenda W J H

PY - 2017/8

Y1 - 2017/8

N2 - In 2009, the first genome-wide association study (GWAS) for major depressive disorder (MDD) highlighted an association with PCLO locus on chromosome 7, although not reaching genome-wide significance level. In the present study, we revisited the original GWAS after increasing the overall sample size and the number of interrogated SNPs. In an analysis comparing 1,942 cases with lifetime diagnosis of MDD and 4,565 controls, PCLO showed a genome-wide significant association with MDD at SNP (rs2715157, p = 2.91 × 10-8) and gene-based (p = 1.48 × 10-7) level. Our results confirm the potential role of the PCLO gene in MDD, which is worth further replication and functional studies.

AB - In 2009, the first genome-wide association study (GWAS) for major depressive disorder (MDD) highlighted an association with PCLO locus on chromosome 7, although not reaching genome-wide significance level. In the present study, we revisited the original GWAS after increasing the overall sample size and the number of interrogated SNPs. In an analysis comparing 1,942 cases with lifetime diagnosis of MDD and 4,565 controls, PCLO showed a genome-wide significant association with MDD at SNP (rs2715157, p = 2.91 × 10-8) and gene-based (p = 1.48 × 10-7) level. Our results confirm the potential role of the PCLO gene in MDD, which is worth further replication and functional studies.

KW - Journal Article

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UR - https://www.scopus.com/pages/publications/85019689051#tab=citedBy

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JO - Twin Research and Human Genetics

JF - Twin Research and Human Genetics

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Genome-Wide Significance for PCLO as a Gene for Major Depressive Disorder

Abstract

Funding

UN SDGs

Keywords

Cohort Studies

Access to Document

Persistent URL (handle)

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