Identification of shared risk loci and pathways for bipolar disorder and schizophrenia

被引：65

作者：

Forstner, Andreas J. ^{[1
,2
,3
,4
,5
]}

Hecker, Julian ^{[6
]}

Hofmann, Andrea ^{[1
,2
,7
]}

Maaser, Anna ^{[1
,2
]}

Reinbold, Celine S. ^{[4
,5
]}

Muehleisen, Thomas W. ^{[1
,2
,4
,5
,8
]}

Leber, Markus ^{[9
]}

Strohmaier, Jana ^{[10
]}

Degenhardt, Franziska ^{[1
,2
]}

Treutlein, Jens ^{[10
]}

Mattheisen, Manuel ^{[1
,11
,12
,13
,14
]}

Schumacher, Johannes ^{[1
,2
]}

Streit, Fabian ^{[10
]}

Meier, Sandra ^{[10
,13
,14
,15
]}

Herms, Stefan ^{[1
,2
,4
,5
]}

Hoffmann, Per ^{[1
,2
,4
,5
]}

Lacour, Andre ^{[16
]}

Witt, Stephanie H. ^{[10
]}

Reif, Andreas ^{[17
]}

Mueller-Myhsok, Bertram ^{[18
,19
,20
]}

Lucae, Susanne ^{[18
]}

Maier, Wolfgang ^{[21
]}

Schwarz, Markus ^{[22
]}

Vedder, Helmut ^{[22
]}

Kammerer-Ciernioch, Jutta ^{[23
]}

Pfennig, Andrea ^{[24
]}

Bauer, Michael ^{[24
]}

Hautzinger, Martin ^{[25
]}

Moebus, Susanne ^{[26
]}

Schenk, Lorena M. ^{[1
,2
]}

Fischer, Sascha B. ^{[4
,5
]}

Sivalingam, Sugirthan ^{[1
,2
]}

Czerski, Piotr M. ^{[27
]}

Hauser, Joanna ^{[27
]}

Lissowska, Jolanta ^{[28
,29
]}

Szeszenia-Dabrowska, Neonila ^{[30
]}

Brennan, Paul ^{[31
]}

McKay, James D. ^{[32
]}

Wright, Adam ^{[33
,34
]}

Mitchell, Philip B. ^{[33
,34
]}

Fullerton, Janice M. ^{[35
,36
]}

Schofield, Peter R. ^{[35
,36
]}

Montgomery, Grant W. ^{[37
]}

Medland, Sarah E. ^{[37
]}

Gordon, Scott D. ^{[37
]}

Martin, Nicholas G. ^{[37
]}

Krasnov, Valery ^{[38
]}

Chuchalin, Alexander ^{[39
]}

Babadjanova, Gulja ^{[39
]}

Pantelejeva, Galina ^{[40
]}

机构：

[1] Univ Bonn, Inst Human Genet, Bonn, Germany

[2] Univ Bonn, Dept Gen Life & Brain Ctr, Bonn, Germany

[3] Univ Basel, Dept Psychiat, Basel, Switzerland

[4] Univ Basel, Dept Biomed, Human Genom Res Grp, Basel, Switzerland

[5] Univ Basel Hosp, Inst Med Genet & Pathol, Basel, Switzerland

[6] Univ Bonn, Inst Genom Math, Bonn, Germany

[7] Univ Bonn, Inst Med Microbiol Immunol & Parasitol, Bonn, Germany

[8] Res Ctr Juelich, Inst Neurosci & Med INM 1, Julich, Germany

[9] Univ Cologne, Dept Psychiat & Psychotherapy, Cologne, Germany

[10] Heidelberg Univ, Med Fac Mannheim, Cent Inst Mental Hlth, Dept Genet Epidemiol Psychiat, Mannheim, Germany

[11] Aarhus Univ, iSEQ, Dept Biomed, Aarhus, Denmark

[12] Aarhus Univ, iSEQ, Ctr Integrat Sequencing, Aarhus, Denmark

[13] iPSYCH, Lundbeck Fdn Initiat Integrat Psychiat Res, Aarhus, Denmark

[14] iPSYCH, Lundbeck Fdn Initiat Integrat Psychiat Res, Copenhagen, Denmark

[15] Aarhus Univ, Natl Ctr Register Based Res, Aarhus, Denmark

[16] German Ctr Neurodegenerat Dis DZNE, Bonn, Germany

[17] Univ Hosp Frankfurt Am Main, Dept Psychiat Psychosomat Med & Psychotherapy, Frankfurt, Germany

[18] Max Planck Inst Psychiat, Munich, Germany

[19] Munich Cluster Syst Neurol SyNergy, Munich, Germany

[20] Univ Liverpool, Inst Translat Med, Liverpool, Merseyside, England

[21] Univ Bonn, Dept Psychiat, Bonn, Germany

[22] Psychiat Ctr Nordbaden, Wiesloch, Germany

[23] Ctr Psychiat Weinsberg, Weinsberg, Germany

[24] Tech Univ Dresden, Univ Hosp Carl Gustav Carus, Dept Psychiat & Psychotherapy, Dresden, Germany

[25] Univ Tubingen, Dept Psychol Clin Psychol & Psychotherapy, Tubingen, Germany

[26] Univ Duisburg Essen, Inst Med Informat Biometry & Epidemiol, Essen, Germany

[27] Poznan Univ Med Sci, Dept Psychiat, Lab Psychiat Genet, Poznan, Poland

[28] Maria Sklodowska Curie Mem Canc Ctr, Dept Canc Epidemiol & Prevent, Warsaw, Poland

[29] Inst Oncol Warsaw, Warsaw, Poland

[30] Nofer Inst Occupat Med, Dept Epidemiol, Lodz, Poland

[31] Int Agcy Res Canc, Genet Epidemiol Grp, Lyon, France

[32] Int Agcy Res Canc, Genet Canc Susceptibil Grp, Lyon, France

[33] Univ New S Wales, Sch Psychiat, Randwick, NSW, Australia

[34] Prince Wales Hosp, Black Dog Inst, Randwick, NSW, Australia

[35] Neurosci Res Australia, Sydney, NSW, Australia

[36] Univ New S Wales, Fac Med, Sch Med Sci, Sydney, NSW, Australia

[37] Queensland Inst Med Res, Brisbane, Qld, Australia

[38] Moscow Res Inst Psychiat, Moscow, Russia

[39] Russian State Med Univ, Inst Pulmonol, Moscow, Russia

[40] Russian Acad Med Sci, Mental Hlth Res Ctr, Moscow, Russia

[41] Kursk State Med Univ, Dept Biol Med Genet & Ecol, Kursk, Russia

[42] Kursk State Med Univ, Res Inst Genet & Mol Epidemiol, Kursk, Russia

[43] Russian Acad Sci, Ufa Sci Ctr, Inst Biochem & Genet, Ufa, Russia

[44] Bashkir State Univ, Dept Genet & Fundamental Med, Ufa, Russia

[45] Dalhousie Univ, Dept Psychiat, Halifax, NS, Canada

[46] NIMH, Klecany, Czech Republic

[47] McGill Univ, Montreal Neurol Inst, Montreal, PQ, Canada

[48] McGill Univ, Dept Human Genet, Montreal, PQ, Canada

[49] McGill Grp Suicide Studies, Montreal, PQ, Canada

[50] Douglas Res Inst, Montreal, PQ, Canada

来源：

PLOS ONE | 2017年 / 12卷 / 02期

基金：

澳大利亚国家健康与医学研究理事会; 瑞士国家科学基金会; 英国惠康基金; 加拿大健康研究院;

关键词：

GENOME-WIDE ASSOCIATION; PREFRONTAL CORTEX; COMMON; ENRICHMENT; GLUTAMATE; NEUROCAN; ETIOLOGY; GENES; SYNE1; TOOL;

D O I：

10.1371/journal.pone.0171595

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

Bipolar disorder (BD) is a highly heritable neuropsychiatric disease characterized by recurrent episodes of mania and depression. BD shows substantial clinical and genetic overlap with other psychiatric disorders, in particular schizophrenia (SCZ). The genes underlying this etiological overlap remain largely unknown. A recent SCZ genome wide association study (GWAS) by the Psychiatric Genomics Consortium identified 128 independent genome-wide significant single nucleotide polymorphisms (SNPs). The present study investigated whether these SCZ-associated SNPs also contribute to BD development through the performance of association testing in a large BD GWAS dataset (9747 patients, 14278 controls). After re-imputation and correction for sample overlap, 22 of 107 investigated SCZ SNPs showed nominal association with BD. The number of shared SCZ-BD SNPs was significantly higher than expected (p = 1.46x10(-8)). This provides further evidence that SCZ-associated loci contribute to the development of BD. Two SNPs remained significant after Bonferroni correction. The most strongly associated SNP was located near TRANK1, which is a reported genome-wide significant risk gene for BD. Pathway analyses for all shared SCZ-BD SNPs revealed 25 nominally enriched gene-sets, which showed partial overlap in terms of the underlying genes. The enriched gene-sets included calcium-and glutamate signaling, neuropathic pain signaling in dorsal horn neurons, and calmodulin binding. The present data provide further insights into shared risk loci and disease-associated pathways for BD and SCZ. This may suggest new research directions for the treatment and prevention of these two major psychiatric disorders.

引用

页数：14

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