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Contributions of common genetic variants to risk of schizophrenia among individuals of African and Latino ancestry.
In: Molecular psychiatry, vol 25, iss 10 (2020)
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.
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
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.
In: Molecular psychiatry, vol 25, iss 10 (2020)
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3
Towards controlled terminology for reporting germline cancer susceptibility variants: an ENIGMA report.
Spurdle, Amanda B; Greville-Heygate, Stephanie; Antoniou, Antonis. - : BMJ, 2019. : J Med Genet, 2019
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4
Genetic regulation in pubertal delay.
Howard, SR. - 2019
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5
Functionally distinct ERAP1 and ERAP2 are a hallmark of HLA-A29-(Birdshot) Uveitis.
In: Human molecular genetics, vol 27, iss 24 (2018)
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6
Genome-wide association meta-analysis in 269,867 individuals identifies new genetic and functional links to intelligence.
In: Nature genetics, vol 50, iss 7 (2018)
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7
Multi-Trait Analysis of GWAS and Biological Insights Into Cognition: A Response to Hill (2018).
In: Twin research and human genetics : the official journal of the International Society for Twin Studies, vol 21, iss 5 (2018)
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8
Cortical responses before 6 months of life associate with later autism. ...
Lloyd-Fox, Sarah; Blasi, A; Pasco, G. - : Apollo - University of Cambridge Repository, 2018
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9
Cortical responses before 6 months of life associate with later autism.
Lloyd-Fox, Sarah; Blasi, A; Pasco, G. - : Wiley, 2018. : Eur J Neurosci, 2018
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10
GWAS meta-analysis reveals novel loci and genetic correlates for general cognitive function: a report from the COGENT consortium.
In: Molecular psychiatry, vol 22, iss 3 (2017)
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11
Language Development and Impairment in Children With Mild to Moderate Sensorineural Hearing Loss. ...
Halliday, Lorna; Tuomainen, Outi; Rosen, Stuart. - : Apollo - University of Cambridge Repository, 2017
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12
Language Development and Impairment in Children With Mild to Moderate Sensorineural Hearing Loss.
Halliday, Lorna; Tuomainen, Outi; Rosen, Stuart. - : American Speech Language Hearing Association, 2017. : J Speech Lang Hear Res, 2017
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13
Dyslexia and language impairment associated genetic markers influence cortical thickness and white matter in typically developing children.
In: Brain imaging and behavior, vol 10, iss 1 (2016)
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14
Rare Inherited and De Novo CNVs Reveal Complex Contributions to ASD Risk in Multiplex Families.
In: American journal of human genetics, vol 99, iss 3 (2016)
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15
Dyslexia and language impairment associated genetic markers influence cortical thickness and white matter in typically developing children.
In: Brain imaging and behavior, vol 10, iss 1 (2016)
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16
Audibility, speech perception and processing of temporal cues in ribbon synaptic disorders due to OTOF mutations.
In: Hearing research, vol 330, iss Pt B (2015)
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17
Differential susceptibility to effects of maternal sensitivity? A study of candidate plasticity genes.
In: Development and psychopathology, vol 27, iss 3 (2015)
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18
Acculturation, Behavioral Factors, and Family History of Breast Cancer among Mexican and Mexican-American Women.
In: Women's health issues : official publication of the Jacobs Institute of Women's Health, vol 25, iss 5 (2015)
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19
Comorbidities in preschool children at family risk of dyslexia.
In: J Child Psychol Psychiatry , 55 (3) 237 - 246. (2014) (2014)
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20
The roles of FMRP-regulated genes in autism spectrum disorder: single- and multiple-hit genetic etiologies.
In: Symplectic Elements at Oxford ; Europe PubMed Central ; PubMed (http://www.ncbi.nlm.nih.gov/pubmed/) ; Web of Science (Lite) (http://apps.webofknowledge.com/summary.do) ; Scopus (http://www.scopus.com/home.url) ; CrossRef (2013)
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