Contributions of common genetic variants to risk of schizophrenia among individuals of African and Latino ancestry
Authors: 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, Calkins Monica E. , Freedman Robert R. , Green Michael F. , Greenwood Tiffany A. , Lazzeroni Laura C. , Light Gregory A. , Nuechterlein Keith H. , Radant Allen D. , Seidman Larry J. , Siever Larry J. , Silverman Jeremy M. , Stone William S. , Sugar Catherine A. , Swerdlow Neal R. , Tsuang Debby W. , Tsuang Ming T. , Turetsky Bruce I. , 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. 
Published: October 2019

AbstractSchizophrenia 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.