1. Contributions of common genetic variants to risk of schizophrenia among individuals of African and Latino ancestry.
- Author
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Bigdeli TB, Genovese G, Georgakopoulos P, Meyers JL, Peterson RE, Iyegbe CO, Medeiros H, Valderrama J, Achtyes ED, Kotov R, Stahl EA, Abbott C, Azevedo MH, Belliveau RA, Bevilacqua E, Bromet EJ, Byerley W, Carvalho CB, Chapman SB, DeLisi LE, Dumont AL, O'Dushlaine C, Evgrafov OV, Fochtmann LJ, Gage D, Kennedy JL, Kinkead B, Macedo A, Moran JL, Morley CP, Dewan MJ, Nemesh J, Perkins DO, Purcell SM, Rakofsky JJ, Scolnick EM, Sklar BM, Sklar P, Smoller JW, Sullivan PF, Macciardi F, Marder SR, Gur RC, Gur RE, Braff DL, Nicolini H, Escamilla MA, Vawter MP, Sobell JL, Malaspina D, Lehrer DS, Buckley PF, Rapaport MH, Knowles JA, Fanous AH, Pato MT, McCarroll SA, and Pato CN
- Subjects
- Female, Genetic Loci, Humans, Male, Polymorphism, Single Nucleotide genetics, Black People genetics, Genetic Predisposition to Disease genetics, Genome-Wide Association Study, Hispanic or Latino genetics, Schizophrenia genetics
- 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 R
2 = 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.- Published
- 2020
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