Contributions of common genetic variants to risk of schizophrenia among individuals of African and Latino ancestry

被引：76

作者：

Bigdeli, Tim B. ^{[1
,2
,3
]}

Genovese, Giulio ^{[4
,5
]}

Georgakopoulos, Penelope ^{[2
]}

Meyers, Jacquelyn L. ^{[1
]}

Peterson, Roseann E. ^{[6
]}

Iyegbe, Conrad O. ^{[7
]}

Medeiros, Helena ^{[2
]}

Valderrama, Jorge ^{[1
,2
]}

Achtyes, Eric D. ^{[8
,9
]}

Kotov, Roman ^{[10
]}

Stahl, Eli A. ^{[11
,12
]}

Abbott, Colony ^{[13
]}

Azevedo, Maria Helena ^{[14
]}

Belliveau, Richard A. ^{[4
]}

Bevilacqua, Elizabeth ^{[15
]}

Bromet, Evelyn J. ^{[10
]}

Byerley, William ^{[16
]}

Carvalho, Celia Barreto ^{[17
]}

Chapman, Sinead B. ^{[4
]}

DeLisi, Lynn E. ^{[18
,19
]}

Dumont, Ashley L. ^{[4
]}

O'Dushlaine, Colm ^{[4
]}

Evgrafov, Oleg V. ^{[2
,20
]}

Fochtmann, Laura J. ^{[10
]}

Gage, Diane ^{[4
]}

Kennedy, James L. ^{[21
,22
]}

Kinkead, Becky ^{[23
]}

Macedo, Antonio ^{[14
]}

Moran, Jennifer L. ^{[4
]}

Morley, Christopher P. ^{[24
,25
,26
]}

Dewan, Mantosh J. ^{[26
]}

Nemesh, James ^{[4
]}

Perkins, Diana O. ^{[27
]}

Purcell, Shaun M. ^{[4
,28
]}

Rakofsky, Jeffrey J. ^{[23
]}

Scolnick, Edward M. ^{[4
]}

Sklar, Brooke M. ^{[13
]}

Sklar, Pamela ^{[11
,12
]}

Smoller, Jordan W. ^{[4
,19
,29
,30
]}

Sullivan, Patrick F. ^{[27
,31
]}

Macciardi, Fabio ^{[32
]}

Marder, Stephen R. ^{[33
,34
]}

Gur, Ruben C. ^{[35
,36
,37
,38
]}

Gur, Raquel E. ^{[35
,36
,37
,38
]}

Braff, David L. ^{[39
,40
]}

Calkins, Monica E. ^{[35
,36
]}

Freedman, Robert R. ^{[45
]}

Green, Michael F. ^{[33
,34
,46
]}

Greenwood, Tiffany A. ^{[39
]}

Lazzeroni, Laura C. ^{[47
,48
]}

机构：

[1] Suny Downstate Med Ctr, Dept Psychiat & Behav Sci, Brooklyn, NY 11203 USA

[2] Suny Downstate Med Ctr, Inst Genom Hlth, Brooklyn, NY 11203 USA

[3] Vet Affairs New York Harbor Healthcare Syst, Dept Psychiat, Brooklyn, NY 11209 USA

[4] Broad Inst MIT & Harvard, Stanley Ctr Psychiat Res, Cambridge, MA 02142 USA

[5] Harvard Med Sch, Dept Genet, Boston, MA 02115 USA

[6] Virginia Commonwealth Univ, Dept Psychiat, Richmond, VA USA

[7] Kings Coll London, Dept Psychosis Studies, London, England

[8] Cherry Hlth, Grand Rapids, MI USA

[9] Michigan State Univ, Coll Human Med, Grand Rapids, MI USA

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

[11] Icahn Sch Med Mt Sinai, Dept Psychiat, Mt Sinai, NY USA

[12] Icahn Sch Med Mt Sinai, Dept Genet & Genom, Mt Sinai, NY USA

[13] Univ Southern Calif, Dept Psychiat & Behav Sci, Los Angeles, CA 90007 USA

[14] Univ Coimbra, Fac Med, Inst Med Psychol, Coimbra, PT, Portugal

[15] Beacon Hlth Opt, Boston, MA USA

[16] Univ Calif San Francisco, Dept Psychiat, San Francisco, CA 94143 USA

[17] Univ Azores, Fac Social & Human Sci, Ponta Delgada, Portugal

[18] VA Boston Healthcare Syst, Brockton, MA USA

[19] Harvard Med Sch, Dept Psychiat, Boston, MA 02115 USA

[20] Suny Downstate Med Ctr, Dept Cell Biol, Brooklyn, NY 11203 USA

[21] Univ Toronto, Neurogenet Lab, Campbell Family Mental Hlth Res Inst, Ctr Addict & Mental Hlth, Toronto, ON, Canada

[22] Univ Toronto, Dept Psychiat, Toronto, ON, Canada

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

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

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

[26] SUNY Upstate Med Univ, Dept Psychiat & Behav Sci, Syracuse, NY 13210 USA

[27] Univ N Carolina, Dept Psychiat, Chapel Hill, NC 27515 USA

[28] Brigham & Womens Hosp, Dept Psychiat, 75 Francis St, Boston, MA 02115 USA

[29] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA

[30] Harvard TH Chan Sch Publ Hlth, Dept Epidemiol, Boston, MA USA

[31] Karolinska Inst, Med Epidemiol & Biostat, Solna, Sweden

[32] Univ Calif Irvine, Dept Psychiat & Human Behav, Irvine, CA 92717 USA

[33] Univ Calif Los Angeles, Dept Psychiat & Biobehav Sci, Geffen Sch Med, Los Angeles, CA 90024 USA

[34] Univ Calif Los Angeles, Semel Inst Neurosci & Human Behav, Geffen Sch Med, Los Angeles, CA USA

[35] Univ Penn, Dept Psychiat, Perelman Sch Med, Philadelphia, PA 19104 USA

[36] Childrens Hosp Philadelphia, Philadelphia, PA 19104 USA

[37] Univ Penn, Child & Adolescent Psychiat, Perelman Sch Med, Philadelphia, PA 19104 USA

[38] Univ Penn, Lifespan Brain Inst, Perelman Sch Med, Philadelphia, PA 19104 USA

[39] Univ Calif San Diego, Dept Psychiat, La Jolla, CA 92093 USA

[40] VA San Diego Healthcare Syst, Res Educ & Clin Ctr MIRECC, VISN 22 Mental Illness, San Diego, CA USA

[41] Carracci Med Grp, Mexico City, DF, Mexico

[42] Texas Tech Univ, Hlth Sci Ctr, Dept Psychiat, El Paso, TX USA

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

[44] Virginia Commonwealth Univ, Sch Med, Richmond, VA USA

[45] Univ Colorado Denver, Dept Psychiat, Aurora, CO USA

[46] VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA

[47] Stanford Univ, Dept Psychiat & Behav Sci, Stanford, CA 94305 USA

[48] Stanford Univ, Dept Pediat, Stanford, CA 94305 USA

[49] Univ Washington, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA

[50] VA Puget Sound Hlth Care Syst, Seattle, WA USA

来源：

MOLECULAR PSYCHIATRY | 2020年 / 25卷 / 10期

基金：

美国国家卫生研究院;

关键词：

GENOME-WIDE ASSOCIATION; LOCI; SUSCEPTIBILITY; METAANALYSIS; MUTATIONS; BURDEN; TRAIT; SET;

D O I：

10.1038/s41380-019-0517-y

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Schizophrenia is a common, chronic and debilitating neuropsychiatric syndrome affecting tens of millions of individuals worldwide. While rare genetic variants play a role in the etiology of schizophrenia, most of the currently explained liability is within common variation, suggesting that variation predating the human diaspora out of Africa harbors a large fraction of the common variant attributable heritability. However, common variant association studies in schizophrenia have concentrated mainly on cohorts of European descent. We describe genome-wide association studies of 6152 cases and 3918 controls of admixed African ancestry, and of 1234 cases and 3090 controls of Latino ancestry, representing the largest such study in these populations to date. Combining results from the samples with African ancestry with summary statistics from the Psychiatric Genomics Consortium (PGC) study of schizophrenia yielded seven newly genome-wide significant loci, and we identified an additional eight loci by incorporating the results from samples with Latino ancestry. Leveraging population differences in patterns of linkage disequilibrium, we achieve improved fine-mapping resolution at 22 previously reported and 4 newly significant loci. Polygenic risk score profiling revealed improved prediction based on trans-ancestry meta-analysis results for admixed African (Nagelkerke'sR(2) = 0.032; liabilityR(2) = 0.017;P < 10(-52)), Latino (Nagelkerke'sR(2) = 0.089; liabilityR(2) = 0.021;P < 10(-58)), and European individuals (Nagelkerke'sR(2) = 0.089; liabilityR(2) = 0.037;P < 10(-113)), further highlighting the advantages of incorporating data from diverse human populations.

引用

页码：2455 / 2467

页数：13

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