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Transl Psychiatry. 2017 Dec 11;7(12):1273. doi: 10.1038/s41398-017-0019-0.

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

Author information

1
Key Laboratory of Animal Models and Human Disease Mechanisms of the Chinese Academy of Sciences and Yunnan Province, Kunming Institute of Zoology, Kunming, Yunnan, China.
2
Department of Pharmacology, Provincial Key Laboratory of Pathophysiology, Ningbo University School of Medicine, Ningbo, Zhejiang, China.
3
Shanghai Key Laboratory of Psychotic Disorders, Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
4
Ningbo Kangning Hospital, Ningbo, Zhejiang, China.
5
Brainnetome Center, Institute of Automation, Chinese Academy of Sciences, Beijing, China.
6
Biometric Psychiatric Genetics Research Unit, Alexandru Obregia Clinical Psychiatric Hospital, Bucharest, Romania.
7
Department of Psychiatry, Fujita Health University School of Medicine, Toyoake, Aichi, Japan.
8
Laboratory for Statistical Analysis, RIKEN Center for Integrative Medical Sciences, Yokohama, Japan.
9
Laboratory for Omics Informatics, Omics Research Center, National Cerebral and Cardiovascular Center, Osaka, Japan.
10
RIKEN Center for Integrative Medical Sciences, Yokohama, Japan.
11
Department of Psychiatry, Centre Hospitalier Universitaire Vaudois, Prilly, Switzerland.
12
Institute of Social and Preventive Medicine, Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland.
13
Swiss Institute of Bioinformatics, Lausanne, Switzerland.
14
Department of Epidemiology, Erasmus University Medical Center, Rotterdam, The Netherlands.
15
Institute of Human Genetics, University of Bonn, Bonn, Germany.
16
Department of Genomics, Life and Brain Center, University of Bonn, Bonn, Germany.
17
Human Genomics Research Group, Department of Biomedicine, University of Basel, Basel, Switzerland.
18
Department of Psychiatry (UPK), University of Basel, Basel, Switzerland.
19
Institute of Medical Genetics and Pathology, University Hospital Basel, Basel, Switzerland.
20
Department of Genetic Epidemiology in Psychiatry, Central Institute of Mental Health, Medical Faculty Mannheim, University of Heidelberg, Mannheim, Germany.
21
Institute of Genomic Mathematics, University of Bonn, Bonn, Germany.
22
Institute of Psychiatric Phenomics and Genomics, Ludwig-Maximilians-University Munich, Munich, Germany.
23
Max Planck Institute of Psychiatry, Munich, Germany.
24
Munich Cluster for Systems Neurology (SyNergy), Munich, Germany.
25
University of Liverpool, Institute of Translational Medicine, Liverpool, UK.
26
Department of Psychiatry, Psychosomatic Medicine and Psychotherapy, University Hospital Frankfurt, Frankfurt, Germany.
27
School of Psychiatry, University of New South Wales, Sydney, NSW, Australia.
28
Black Dog Institute, Sydney, NSW, Australia.
29
QIMR Berghofer Medical Research Institute, Brisbane, QLD, Australia.
30
Neuroscience Research Australia, Sydney, NSW, Australia.
31
School of Medical Sciences, University of New South Wales, Sydney, NSW, Australia.
32
Institute of Neuroscience and Medicine (INM-1), Structural and Functional Organization of the Brain, Genomic Imaging, Research Centre Jülich, Jülich, Germany.
33
Division of Mood Disorders, Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
34
CAS Center for Excellence in Brain Science and Intelligence Technology, Chinese Academy of Sciences, Shanghai, China.
35
Key Laboratory of Animal Models and Human Disease Mechanisms of the Chinese Academy of Sciences and Yunnan Province, Kunming Institute of Zoology, Kunming, Yunnan, China. limingkiz@mail.kiz.ac.cn.
36
CAS Center for Excellence in Brain Science and Intelligence Technology, Chinese Academy of Sciences, Shanghai, China. limingkiz@mail.kiz.ac.cn.

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.

PMID:
29225345
PMCID:
PMC5802692
DOI:
10.1038/s41398-017-0019-0
[Indexed for MEDLINE]
Free PMC Article

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