Evidence for genetic heterogeneity between clinical subtypes of bipolar disorder

被引：136

作者：

Charney, A. W. ^{[1
]}

Ruderfer, D. M. ^{[1
,2
]}

Stahl, E. A. ^{[1
,2
]}

Moran, J. L. ^{[3
,4
]}

Chambert, K. ^{[3
,4
]}

Belliveau, R. A. ^{[3
,4
]}

Forty, L. ^{[5
]}

Gordon-Smith, K. ^{[6
]}

Di Florio, A. ^{[5
,6
]}

Lee, P. H. ^{[3
,4
,8
,9
]}

Bromet, E. J. ^{[10
]}

Buckley, P. F. ^{[11
]}

Escamilla, M. A. ^{[12
]}

Fanous, A. H. ^{[13
,14
]}

Fochtmann, L. J. ^{[10
]}

Lehrer, D. S. ^{[15
]}

Malaspina, D. ^{[16
]}

Marder, S. R. ^{[17
]}

Morley, C. P. ^{[18
,19
,20
]}

Nicolini, H. ^{[21
,22
]}

Perkins, D. O. ^{[7
]}

Rakofsky, J. J. ^{[23
]}

Rapaport, M. H.

Medeiros, H.

Sobell, J. L. ^{[24
]}

Green, E. K. ^{[25
]}

Backlund, L. ^{[26
,27
]}

Bergen, S. E. ^{[2
,28
]}

Jureus, A. ^{[28
]}

Schalling, M.

Lichtenstein, P. ^{[28
]}

Roussos, P. ^{[1
,2
]}

Knowles, J. A. ^{[29
]}

Jones, I.

Jones, L. A.

Hultman, C. M. ^{[1
]}

Perlis, R. H. ^{[30
]}

Purcell, S. M. ^{[1
,2
]}

McCarroll, S. A. ^{[2
,31
]}

Pato, C. N. ^{[29
]}

Pato, M. T.

Craddock, N.

Landen, M. ^{[28
,32
]}

Smoller, J. W. ^{[2
,9
,33
]}

Sklar, P.

机构：

[1] Icahn Sch Med Mt Sinai, Dept Psychiat, 1 Gustave L Levy Pl, New York, NY 10029 USA

[2] Icahn Sch Med Mt Sinai, Dept Genet & Genom Sci, Inst Genom & Multiscale Biol, 1 Gustave L Levy Pl, New York, NY 10029 USA

[3] Broad Inst Harvard, Stanley Ctr Psychiat Res, Cambridge, MA USA

[4] MIT, 77 Massachusetts Ave, Cambridge, MA 02139 USA

[5] Cardiff Unviers, MRC Ctr Psychiat Genet & Genom, Cardiff, S Glam, Wales

[6] Univ Worcester, Dept Psychol Med, Worcester, England

[7] Univ N Carolina, Dept Psychiat, Chapel Hill, NC USA

[8] Harvard Med Sch, Dept Psychiat, Boston, MA USA

[9] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA

[10] SUNY Stony Brook, Dept Psychiat, Stony Brook, NY 11794 USA

[11] Georgia Regents Univ, Med Ctr, Dept Psychiat, Augusta, GA USA

[12] Texas Tech Univ, Hlth Sci Ctr, Dept Psychiat, Ctr Excellence Neurosci, El Paso, TX USA

[13] Vet Adm Med Ctr, Dept Psychiat, Washington, DC 20422 USA

[14] Georgetown Univ, Dept Psychiat, Washington, DC USA

[15] Wright State Univ, Dept Psychiat, Dayton, OH 45435 USA

[16] NYU, Dept Psychiat, 550 1St Ave, New York, NY 10016 USA

[17] Univ Calif Los Angeles, Dept Psychiat, Los Angeles, CA USA

[18] SUNY Upstate Med Univ, Dept Psychiat & Behav Neurosci, Syracuse, NY 13210 USA

[19] SUNY Upstate Med Univ, Dept Family Med, Syracuse, NY 13210 USA

[20] SUNY Upstate Med Univ, Dept Publ Hlth & Prevent Med, Syracuse, NY 13210 USA

[21] Univ Autonoma Ciudad Mexico, Ctr Genom Sci, Mexico City, DF, Mexico

[22] Carracci Med Grp, Dept Psychiat, Mexico City, DF, Mexico

[23] Emory Univ, Dept Psychiat & Behav Sci, Atlanta, GA 30322 USA

[24] Univ Southern Calif, Keck Sch Med, Dept Psychiat & Behav Sci, Los Angeles, CA 90033 USA

[25] Univ Plymouth, Peninsula Schools Med & Dent, Sch Biomed & Hlth Sci, Plymouth, Devon, England

[26] Karolinska Inst, Dept Clin Neurosci, Stockholm, Sweden

[27] Karolinska Inst, Dept Mol Med & Surg, Stockholm, Sweden

[28] Karolinska Inst, Dept Med Epidemiol & Biostat, Stockholm, Sweden

[29] Univ Southern Calif, Keck Sch Med, Zilkha Neurogenet Inst, Los Angeles, CA 90033 USA

[30] Massachusetts Gen Hosp, Ctr Expt Therapeut, Boston, MA 02114 USA

[31] Harvard Med Sch, Dept Genet, Boston, MA USA

[32] Gothenburg Univ, Sahlgenska Acad, Inst Neurosci Physiol, Gothenburg, Sweden

[33] Massachusetts Gen Hosp, Ctr Human Genet Res, Psychiat & Neurodevelopmental Genet Unit, Boston, MA 02114 USA

来源：

TRANSLATIONAL PSYCHIATRY | 2017年 / 7卷

基金：

美国国家卫生研究院; 英国医学研究理事会; 英国惠康基金; 瑞典研究理事会;

关键词：

GENOME-WIDE ASSOCIATION; SPECTRUM DISORDER; RISK LOCI; SCHIZOPHRENIA; FAMILY; DEPRESSION; UNIPOLAR; SUSCEPTIBILITY; PREVALENCE; SEVERITY;

D O I：

10.1038/tp.2016.242

中图分类号：

R749 [精神病学];

学科分类号：

100205 ;

摘要：

We performed a genome-wide association study of 6447 bipolar disorder (BD) cases and 12 639 controls from the International Cohort Collection for Bipolar Disorder (ICCBD). Meta-analysis was performed with prior results from the Psychiatric Genomics Consortium Bipolar Disorder Working Group for a combined sample of 13 902 cases and 19 279 controls. We identified eight genome-wide significant, associated regions, including a novel associated region on chromosome 10 (rs10884920; P = 3.28 x 10(-8)) that includes the brain-enriched cytoskeleton protein adducin 3 (ADD3), a non-coding RNA, and a neuropeptide-specific aminopeptidase P (XPNPEP1). Our large sample size allowed us to test the heritability and genetic correlation of BD subtypes and investigate their genetic overlap with schizophrenia and major depressive disorder. We found a significant difference in heritability of the two most common forms of BD (BD I SNP-h(2) = 0.35; BD II SNP-h(2) = 0.25; P = 0.02). The genetic correlation between BD I and BD II was 0.78, whereas the genetic correlation was 0.97 when BD cohorts containing both types were compared. In addition, we demonstrated a significantly greater load of polygenic risk alleles for schizophrenia and BD in patients with BD I compared with patients with BD II, and a greater load of schizophrenia risk alleles in patients with the bipolar type of schizoaffective disorder compared with patients with either BD I or BD II. These results point to a partial difference in the genetic architecture of BD subtypes as currently defined.

引用

页码：e993 / e993

页数：9

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