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Mol Psychiatry. 2019 Oct 7. doi: 10.1038/s41380-019-0517-y. [Epub ahead of print]

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

Author information

1
Department of Psychiatry and Behavioral Sciences, SUNY Downstate Medical Center, Brooklyn, NY, USA. tim.bigdeli@downstate.edu.
2
Institute for Genomic Health, SUNY Downstate Medical Center, Brooklyn, NY, USA. tim.bigdeli@downstate.edu.
3
Department of Psychiatry, Veterans Affairs New York Harbor Healthcare System, Brooklyn, NY, USA. tim.bigdeli@downstate.edu.
4
Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, MA, USA.
5
Department of Genetics, Harvard Medical School, Boston, MA, USA.
6
Institute for Genomic Health, SUNY Downstate Medical Center, Brooklyn, NY, USA.
7
Department of Psychiatry and Behavioral Sciences, SUNY Downstate Medical Center, Brooklyn, NY, USA.
8
Department of Psychiatry, Virginia Commonwealth University, Richmond, VA, USA.
9
Department of Psychosis Studies, King's College London, London, UK.
10
Cherry Health and Michigan State University College of Human Medicine, Grand Rapids, MI, USA.
11
Department of Psychiatry, Stony Brook University, Stony Brook, NY, USA.
12
Department of Psychiatry, Icahn School of Medicine at Mount Sinai, Mount Sinai, NY, USA.
13
Department of Genetics & Genomics, Icahn School of Medicine at Mount Sinai, Mount Sinai, NY, USA.
14
Department of Psychiatry & Behavioral Sciences, University of Southern California, Los Angeles, CA, USA.
15
Institute of Medical Psychology, Faculty of Medicine, University of Coimbra, Coimbra, PT, Portugal.
16
Beacon Health Options, Boston, MA, USA.
17
Department of Psychiatry, University of California, San Francisco, CA, USA.
18
Faculty of Social and Human Sciences, University of Azores, Ponta Delgada, Portugal.
19
VA Boston Healthcare System, Brockton, MA, USA.
20
Department of Psychiatry, Harvard Medical School, Boston, MA, USA.
21
Department of Cell Biology, SUNY Downstate Medical Center, Brooklyn, NY, USA.
22
Neurogenetics Laboratory, Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health; Department of Psychiatry, University of Toronto, Toronto, ON, Canada.
23
Department of Psychiatry and Behavioral Sciences, Emory University, Atlanta, GA, USA.
24
Department of Public Health and Preventive Medicine, State University of New York, Upstate Medical University, Syracuse, NY, USA.
25
Department of Family Medicine, State University of New York, Upstate Medical University, Syracuse, NY, USA.
26
Department of Psychiatry and Behavioral Sciences, State University of New York, Upstate Medical University, Syracuse, NY, USA.
27
Department of Psychiatry, University of North Carolina, Chapel Hill, NC, USA.
28
Department of Psychiatry, Brigham and Women's Hospital, Boston, MA, USA.
29
Department of Psychiatry, Massachusetts General Hospital, Boston, MA, USA.
30
Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, USA.
31
Medical Epidemiology and Biostatistics, Karolinska Institutet, Solna, SE, Sweden.
32
Department of Psychiatry and Human Behavior, University of California, Irvine, CA, USA.
33
Department of Psychiatry and Biobehavioral Sciences, Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA, USA.
34
Semel Institute for Neuroscience and Human Behavior, Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA, USA.
35
Department of Psychiatry, University of Pennsylvania Perelman School of Medicine and Children's Hospital of Philadelphia, Philadelphia, PA, USA.
36
Child & Adolescent Psychiatry, University of Pennsylvania Perelman School of Medicine and Children's Hospital of Philadelphia, Philadelphia, PA, USA.
37
Lifespan Brain Institute, University of Pennsylvania Perelman School of Medicine and Children's Hospital of Philadelphia, Philadelphia, PA, USA.
38
Department of Psychiatry, University of California, La Jolla, San Diego, CA, USA.
39
VISN-22 Mental Illness, Research, Education and Clinical Center (MIRECC), VA San Diego Healthcare System, San Diego, CA, USA.
40
Carracci Medical Group, Mexico City, MX, Mexico.
41
Department of Psychiatry, Texas Tech University Health Sciences Center, El Paso, TX, USA.
42
Department of Psychiatry, Wright State University, Dayton, OH, USA.
43
School of Medicine, Virginia Commonwealth University, Richmond, VA, USA.
44
Department of Psychiatry, Veterans Affairs New York Harbor Healthcare System, Brooklyn, NY, USA.

Abstract

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's R2 = 0.032; liability R2 = 0.017; P < 10-52), Latino (Nagelkerke's R2 = 0.089; liability R2 = 0.021; P < 10-58), and European individuals (Nagelkerke's R2 = 0.089; liability R2 = 0.037; P < 10-113), further highlighting the advantages of incorporating data from diverse human populations.

PMID:
31591465
DOI:
10.1038/s41380-019-0517-y

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