Contributions of common genetic variants to risk of schizophrenia among individuals of African and Latino ancestry.
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Author
Bigdeli, Tim BGenovese, 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
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
Fanous, Ayman H
Pato, Michele T
McCarroll, Steven A
Pato, Carlos N
Journal title
Molecular psychiatryDate Published
2019-10-07Publication Volume
25Publication Issue
10Publication Begin page
2455Publication End page
2467
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Show full item recordAbstract
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 = 0.032; liability R = 0.017; P < 10), Latino (Nagelkerke's R = 0.089; liability R = 0.021; P < 10), and European individuals (Nagelkerke's R = 0.089; liability R = 0.037; P < 10), further highlighting the advantages of incorporating data from diverse human populations.Citation
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; Consortium on the Genetics of Schizophrenia (COGS) Investigators; Nicolini H, Escamilla MA, Vawter MP, Sobell JL, Malaspina D, Lehrer DS, Buckley PF, Rapaport MH, Knowles JA; Genomic Psychiatry Cohort (GPC) Consortium; Fanous AH, Pato MT, McCarroll SA, Pato CN. Contributions of common genetic variants to risk of schizophrenia among individuals of African and Latino ancestry. Mol Psychiatry. 2020 Oct;25(10):2455-2467. doi: 10.1038/s41380-019-0517-y. Epub 2019 Oct 7. PMID: 31591465; PMCID: PMC7515843.DOI
10.1038/s41380-019-0517-yae974a485f413a2113503eed53cd6c53
10.1038/s41380-019-0517-y
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