Common variants at 2q11.2, 8q21.3, and 11q13.2 are associated with major mood disorders

Xiao Xiao, Lu Wang, Chuang Wang, Ti Fei Yuan, Dongsheng Zhou, Fanfan Zheng, Lingyi Li, Maria Grigoroiu-Serbanescu, Masashi Ikeda, Nakao Iwata, Atsushi Takahashi, Yoichiro Kamatani, Michiaki Kubo, Martin Preisig, Zoltán Kutalik, Enrique Castelao, Giorgio Pistis, Najaf Amin, Cornelia M. Van Duijn, Andreas J. ForstnerJana Strohmaier, Julian Hecker, Thomas G. Schulze, Bertram Müller-Myhsok, Andreas Reif, Philip B. Mitchell, Nicholas G. Martin, Peter R. Schofield, Sven Cichon, Markus M. Nöthen, Hong Chang, Xiong Jian Luo, Yiru Fang, Yong Gang Yao, Chen Zhang, Marcella Rietschel, Ming Li

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

Bipolar disorder (BPD) and major depressive disorder (MDD) are primary major mood disorders. Recent studies suggest that they share certain psychopathological features and common risk genes, but unraveling the full genetic architecture underlying the risk of major mood disorders remains an important scientific task. The public genome-wide association study (GWAS) data sets offer the opportunity to examine this topic by utilizing large amounts of combined genetic data, which should ultimately allow a better understanding of the onset and development of these illnesses. Genome-wide meta-analysis was performed by combining two GWAS data sets on BPD and MDD (19,637 cases and 18,083 controls), followed by replication analyses for the loci of interest in independent 12,364 cases and 76,633 controls from additional samples that were not included in the two GWAS data sets. The single-nucleotide polymorphism (SNP) rs10791889 at 11q13.2 was significant in both discovery and replication samples. When combining all samples, this SNP and multiple other SNPs at 2q11.2 (rs717454), 8q21.3 (rs10103191), and 11q13.2 (rs2167457) exhibited genome-wide significant association with major mood disorders. The SNPs in 2q11.2 and 8q21.3 were novel risk SNPs that were not previously reported, and SNPs at 11q13.2 were in high LD with potential BPD risk SNPs implicated in a previous GWAS. The genome-wide significant loci at 2q11.2 and 11q13.2 exhibited strong effects on the mRNA expression of certain nearby genes in cerebellum. In conclusion, we have identified several novel loci associated with major mood disorders, adding further support for shared genetic risk between BPD and MDD. Our study highlights the necessity and importance of mining public data sets to explore risk genes for complex diseases such as mood disorders.

Original languageEnglish
Article number1273
JournalTranslational psychiatry
Volume7
Issue number12
DOIs
Publication statusPublished - 01-12-2017

Fingerprint

Mood Disorders
Single Nucleotide Polymorphism
Genome-Wide Association Study
Bipolar Disorder
Major Depressive Disorder
Genome
Genes
Cerebellum
Meta-Analysis
Messenger RNA
Datasets

All Science Journal Classification (ASJC) codes

  • Psychiatry and Mental health
  • Cellular and Molecular Neuroscience
  • Biological Psychiatry

Cite this

Xiao, X., Wang, L., Wang, C., Yuan, T. F., Zhou, D., Zheng, F., ... Li, M. (2017). Common variants at 2q11.2, 8q21.3, and 11q13.2 are associated with major mood disorders. Translational psychiatry, 7(12), [1273]. https://doi.org/10.1038/s41398-017-0019-0
Xiao, Xiao ; Wang, Lu ; Wang, Chuang ; Yuan, Ti Fei ; Zhou, Dongsheng ; Zheng, Fanfan ; Li, Lingyi ; Grigoroiu-Serbanescu, Maria ; Ikeda, Masashi ; Iwata, Nakao ; Takahashi, Atsushi ; Kamatani, Yoichiro ; Kubo, Michiaki ; Preisig, Martin ; Kutalik, Zoltán ; Castelao, Enrique ; Pistis, Giorgio ; Amin, Najaf ; Van Duijn, Cornelia M. ; Forstner, Andreas J. ; Strohmaier, Jana ; Hecker, Julian ; Schulze, Thomas G. ; Müller-Myhsok, Bertram ; Reif, Andreas ; Mitchell, Philip B. ; Martin, Nicholas G. ; Schofield, Peter R. ; Cichon, Sven ; Nöthen, Markus M. ; Chang, Hong ; Luo, Xiong Jian ; Fang, Yiru ; Yao, Yong Gang ; Zhang, Chen ; Rietschel, Marcella ; Li, Ming. / Common variants at 2q11.2, 8q21.3, and 11q13.2 are associated with major mood disorders. In: Translational psychiatry. 2017 ; Vol. 7, No. 12.
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title = "Common variants at 2q11.2, 8q21.3, and 11q13.2 are associated with major mood disorders",
abstract = "Bipolar disorder (BPD) and major depressive disorder (MDD) are primary major mood disorders. Recent studies suggest that they share certain psychopathological features and common risk genes, but unraveling the full genetic architecture underlying the risk of major mood disorders remains an important scientific task. The public genome-wide association study (GWAS) data sets offer the opportunity to examine this topic by utilizing large amounts of combined genetic data, which should ultimately allow a better understanding of the onset and development of these illnesses. Genome-wide meta-analysis was performed by combining two GWAS data sets on BPD and MDD (19,637 cases and 18,083 controls), followed by replication analyses for the loci of interest in independent 12,364 cases and 76,633 controls from additional samples that were not included in the two GWAS data sets. The single-nucleotide polymorphism (SNP) rs10791889 at 11q13.2 was significant in both discovery and replication samples. When combining all samples, this SNP and multiple other SNPs at 2q11.2 (rs717454), 8q21.3 (rs10103191), and 11q13.2 (rs2167457) exhibited genome-wide significant association with major mood disorders. The SNPs in 2q11.2 and 8q21.3 were novel risk SNPs that were not previously reported, and SNPs at 11q13.2 were in high LD with potential BPD risk SNPs implicated in a previous GWAS. The genome-wide significant loci at 2q11.2 and 11q13.2 exhibited strong effects on the mRNA expression of certain nearby genes in cerebellum. In conclusion, we have identified several novel loci associated with major mood disorders, adding further support for shared genetic risk between BPD and MDD. Our study highlights the necessity and importance of mining public data sets to explore risk genes for complex diseases such as mood disorders.",
author = "Xiao Xiao and Lu Wang and Chuang Wang and Yuan, {Ti Fei} and Dongsheng Zhou and Fanfan Zheng and Lingyi Li and Maria Grigoroiu-Serbanescu and Masashi Ikeda and Nakao Iwata and Atsushi Takahashi and Yoichiro Kamatani and Michiaki Kubo and Martin Preisig and Zolt{\'a}n Kutalik and Enrique Castelao and Giorgio Pistis and Najaf Amin and {Van Duijn}, {Cornelia M.} and Forstner, {Andreas J.} and Jana Strohmaier and Julian Hecker and Schulze, {Thomas G.} and Bertram M{\"u}ller-Myhsok and Andreas Reif and Mitchell, {Philip B.} and Martin, {Nicholas G.} and Schofield, {Peter R.} and Sven Cichon and N{\"o}then, {Markus M.} and Hong Chang and Luo, {Xiong Jian} and Yiru Fang and Yao, {Yong Gang} and Chen Zhang and Marcella Rietschel and Ming Li",
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Xiao, X, Wang, L, Wang, C, Yuan, TF, Zhou, D, Zheng, F, Li, L, Grigoroiu-Serbanescu, M, Ikeda, M, Iwata, N, Takahashi, A, Kamatani, Y, Kubo, M, Preisig, M, Kutalik, Z, Castelao, E, Pistis, G, Amin, N, Van Duijn, CM, Forstner, AJ, Strohmaier, J, Hecker, J, Schulze, TG, Müller-Myhsok, B, Reif, A, Mitchell, PB, Martin, NG, Schofield, PR, Cichon, S, Nöthen, MM, Chang, H, Luo, XJ, Fang, Y, Yao, YG, Zhang, C, Rietschel, M & Li, M 2017, 'Common variants at 2q11.2, 8q21.3, and 11q13.2 are associated with major mood disorders', Translational psychiatry, vol. 7, no. 12, 1273. https://doi.org/10.1038/s41398-017-0019-0

Common variants at 2q11.2, 8q21.3, and 11q13.2 are associated with major mood disorders. / Xiao, Xiao; Wang, Lu; Wang, Chuang; Yuan, Ti Fei; Zhou, Dongsheng; Zheng, Fanfan; Li, Lingyi; Grigoroiu-Serbanescu, Maria; Ikeda, Masashi; Iwata, Nakao; Takahashi, Atsushi; Kamatani, Yoichiro; Kubo, Michiaki; Preisig, Martin; Kutalik, Zoltán; Castelao, Enrique; Pistis, Giorgio; Amin, Najaf; Van Duijn, Cornelia M.; Forstner, Andreas J.; Strohmaier, Jana; Hecker, Julian; Schulze, Thomas G.; Müller-Myhsok, Bertram; Reif, Andreas; Mitchell, Philip B.; Martin, Nicholas G.; Schofield, Peter R.; Cichon, Sven; Nöthen, Markus M.; Chang, Hong; Luo, Xiong Jian; Fang, Yiru; Yao, Yong Gang; Zhang, Chen; Rietschel, Marcella; Li, Ming.

In: Translational psychiatry, Vol. 7, No. 12, 1273, 01.12.2017.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Common variants at 2q11.2, 8q21.3, and 11q13.2 are associated with major mood disorders

AU - Xiao, Xiao

AU - Wang, Lu

AU - Wang, Chuang

AU - Yuan, Ti Fei

AU - Zhou, Dongsheng

AU - Zheng, Fanfan

AU - Li, Lingyi

AU - Grigoroiu-Serbanescu, Maria

AU - Ikeda, Masashi

AU - Iwata, Nakao

AU - Takahashi, Atsushi

AU - Kamatani, Yoichiro

AU - Kubo, Michiaki

AU - Preisig, Martin

AU - Kutalik, Zoltán

AU - Castelao, Enrique

AU - Pistis, Giorgio

AU - Amin, Najaf

AU - Van Duijn, Cornelia M.

AU - Forstner, Andreas J.

AU - Strohmaier, Jana

AU - Hecker, Julian

AU - Schulze, Thomas G.

AU - Müller-Myhsok, Bertram

AU - Reif, Andreas

AU - Mitchell, Philip B.

AU - Martin, Nicholas G.

AU - Schofield, Peter R.

AU - Cichon, Sven

AU - Nöthen, Markus M.

AU - Chang, Hong

AU - Luo, Xiong Jian

AU - Fang, Yiru

AU - Yao, Yong Gang

AU - Zhang, Chen

AU - Rietschel, Marcella

AU - Li, Ming

PY - 2017/12/1

Y1 - 2017/12/1

N2 - Bipolar disorder (BPD) and major depressive disorder (MDD) are primary major mood disorders. Recent studies suggest that they share certain psychopathological features and common risk genes, but unraveling the full genetic architecture underlying the risk of major mood disorders remains an important scientific task. The public genome-wide association study (GWAS) data sets offer the opportunity to examine this topic by utilizing large amounts of combined genetic data, which should ultimately allow a better understanding of the onset and development of these illnesses. Genome-wide meta-analysis was performed by combining two GWAS data sets on BPD and MDD (19,637 cases and 18,083 controls), followed by replication analyses for the loci of interest in independent 12,364 cases and 76,633 controls from additional samples that were not included in the two GWAS data sets. The single-nucleotide polymorphism (SNP) rs10791889 at 11q13.2 was significant in both discovery and replication samples. When combining all samples, this SNP and multiple other SNPs at 2q11.2 (rs717454), 8q21.3 (rs10103191), and 11q13.2 (rs2167457) exhibited genome-wide significant association with major mood disorders. The SNPs in 2q11.2 and 8q21.3 were novel risk SNPs that were not previously reported, and SNPs at 11q13.2 were in high LD with potential BPD risk SNPs implicated in a previous GWAS. The genome-wide significant loci at 2q11.2 and 11q13.2 exhibited strong effects on the mRNA expression of certain nearby genes in cerebellum. In conclusion, we have identified several novel loci associated with major mood disorders, adding further support for shared genetic risk between BPD and MDD. Our study highlights the necessity and importance of mining public data sets to explore risk genes for complex diseases such as mood disorders.

AB - Bipolar disorder (BPD) and major depressive disorder (MDD) are primary major mood disorders. Recent studies suggest that they share certain psychopathological features and common risk genes, but unraveling the full genetic architecture underlying the risk of major mood disorders remains an important scientific task. The public genome-wide association study (GWAS) data sets offer the opportunity to examine this topic by utilizing large amounts of combined genetic data, which should ultimately allow a better understanding of the onset and development of these illnesses. Genome-wide meta-analysis was performed by combining two GWAS data sets on BPD and MDD (19,637 cases and 18,083 controls), followed by replication analyses for the loci of interest in independent 12,364 cases and 76,633 controls from additional samples that were not included in the two GWAS data sets. The single-nucleotide polymorphism (SNP) rs10791889 at 11q13.2 was significant in both discovery and replication samples. When combining all samples, this SNP and multiple other SNPs at 2q11.2 (rs717454), 8q21.3 (rs10103191), and 11q13.2 (rs2167457) exhibited genome-wide significant association with major mood disorders. The SNPs in 2q11.2 and 8q21.3 were novel risk SNPs that were not previously reported, and SNPs at 11q13.2 were in high LD with potential BPD risk SNPs implicated in a previous GWAS. The genome-wide significant loci at 2q11.2 and 11q13.2 exhibited strong effects on the mRNA expression of certain nearby genes in cerebellum. In conclusion, we have identified several novel loci associated with major mood disorders, adding further support for shared genetic risk between BPD and MDD. Our study highlights the necessity and importance of mining public data sets to explore risk genes for complex diseases such as mood disorders.

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