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Contributions of common genetic variants to risk of schizophrenia among individuals of African and Latino ancestry.
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Bigdeli, Tim B; Genovese, Giulio; Georgakopoulos, Penelope; Meyers, Jacquelyn L; Peterson, Roseann E; Iyegbe, Conrad O; Medeiros, Helena; Valderrama, Jorge; Achtyes, Eric D; Kotov, Roman; Stahl, Eli A; Abbott, Colony; Azevedo, Maria Helena; Belliveau, Richard A; Bevilacqua, Elizabeth; Bromet, Evelyn J; Byerley, William; Carvalho, Celia Barreto; Chapman, Sinéad B; DeLisi, Lynn E; Dumont, Ashley L; O'Dushlaine, Colm; Evgrafov, Oleg V; Fochtmann, Laura J; Gage, Diane; Kennedy, James L; Kinkead, Becky; Macedo, Antonio; Moran, Jennifer L; Morley, Christopher P; Dewan, Mantosh J; Nemesh, James; Perkins, Diana O; Purcell, Shaun M; Rakofsky, Jeffrey J; Scolnick, Edward M; Sklar, Brooke M; Sklar, Pamela; Smoller, Jordan W; Sullivan, Patrick F; Macciardi, Fabio; Marder, Stephen R; Gur, Ruben C; Gur, Raquel E; Braff, David L; Consortium on the Genetics of Schizophrenia (COGS) Investigators; Nicolini, Humberto; Escamilla, Michael A; Vawter, Marquis P; Sobell, Janet L; Malaspina, Dolores; Lehrer, Douglas S; Buckley, Peter F; Rapaport, Mark H; Knowles, James A; Genomic Psychiatry Cohort (GPC) Consortium; Fanous, Ayman H; Pato, Michele T; McCarroll, Steven A; Pato, Carlos N
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In: Molecular psychiatry, vol 25, iss 10 (2020)
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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.
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Keyword:
2.1 Biological and endogenous factors; African Continental Ancestry Group; Biological Sciences; Brain Disorders; Clinical Research; Consortium on the Genetics of Schizophrenia (COGS) Investigators; Female; Genetic Loci; Genetic Predisposition to Disease; Genetics; Genome-Wide Association Study; Genomic Psychiatry Cohort (GPC) Consortium; Hispanic Americans; Human Genome; Humans; Male; Medical and Health Sciences; Mental Health; Polymorphism; Psychiatry; Psychology and Cognitive Sciences; Schizophrenia; Serious Mental Illness; Single Nucleotide
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URL: https://escholarship.org/uc/item/5gk7n9bq
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| 2 |
Contributions of common genetic variants to risk of schizophrenia among individuals of African and Latino ancestry.
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In: Molecular psychiatry, vol 25, iss 10 (2020)
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