title: GWAS meta-analysis reveals novel loci and genetic correlates for general cognitive function: a report from the COGENT consortium.
abstract: The complex nature of human cognition has resulted in cognitive genomics lagging behind many other fields in terms of gene discovery using genome-wide association study (GWAS) methods. In an attempt to overcome these barriers, the current study utilized GWAS meta-analysis to examine the association of common genetic variation (~8M single-nucleotide polymorphisms (SNP) with minor allele frequency ⩾1%) to general cognitive function in a sample of 35 298 healthy individuals of European ancestry across 24 cohorts in the Cognitive Genomics Consortium (COGENT). In addition, we utilized individual SNP lookups and polygenic score analyses to identify genetic overlap with other relevant neurobehavioral phenotypes. Our primary GWAS meta-analysis identified two novel SNP loci (top SNPs: rs76114856 in the CENPO gene on chromosome 2 and rs6669072 near LOC105378853 on chromosome 1) associated with cognitive performance at the genome-wide significance level (P<5 × 10-8). Gene-based analysis identified an additional three Bonferroni-corrected significant loci at chromosomes 17q21.31, 17p13.1 and 1p13.3. Altogether, common variation across the genome resulted in a conservatively estimated SNP heritability of 21.5% (s.e.=0.01%) for general cognitive function. Integration with prior GWAS of cognitive performance and educational attainment yielded several additional significant loci. Finally, we found robust polygenic correlations between cognitive performance and educational attainment, several psychiatric disorders, birth length/weight and smoking behavior, as well as a novel genetic association to the personality trait of openness. These data provide new insight into the genetics of neurocognitive function with relevance to understanding the pathophysiology of neuropsychiatric illness.
authors.affiliation: Division of Psychiatry Research, Zucker Hillside Hospital, Glen Oaks, NY, USA.
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authors.affiliation: Division of Psychiatry Research, Zucker Hillside Hospital, Glen Oaks, NY, USA.|Center for Psychiatric Neuroscience, Feinstein Institute for Medical Research, Manhasset, NY, USA.
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authors.affiliation: Department of Psychology, University of Edinburgh, Edinburgh, UK.
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authors.affiliation: NORMENT, K.G. Jebsen Centre for Psychosis Research, University of Bergen, Bergen, Norway.|Division of Mental Health and Addiction, Oslo University Hospital, Oslo, Norway.
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authors.affiliation: Division of Mental Health and Addiction, Oslo University Hospital, Oslo, Norway.|Department of Psychology, University of Oslo, Oslo, Norway.
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authors.affiliation: NORMENT, K.G. Jebsen Centre for Psychosis Research, University of Bergen, Bergen, Norway.|Dr Einar Martens Research Group for Biological Psychiatry, Center for Medical Genetics and Molecular Medicine, Haukeland University Hospital, Bergen, Norway.
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authors.affiliation: Department of Psychology, University of Oslo, Oslo, Norway.
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authors.affiliation: Division of Psychiatry Research, Zucker Hillside Hospital, Glen Oaks, NY, USA.|Center for Psychiatric Neuroscience, Feinstein Institute for Medical Research, Manhasset, NY, USA.
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authors.affiliation: NORMENT, K.G. Jebsen Centre for Psychosis Research, University of Bergen, Bergen, Norway.|Dr Einar Martens Research Group for Biological Psychiatry, Center for Medical Genetics and Molecular Medicine, Haukeland University Hospital, Bergen, Norway.
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authors.affiliation: Division of Mental Health and Addiction, Oslo University Hospital, Oslo, Norway.|Department of Psychology, University of Oslo, Oslo, Norway.
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authors.affiliation: NORMENT, K.G. Jebsen Centre for Psychosis Research, University of Bergen, Bergen, Norway.|Dr Einar Martens Research Group for Biological Psychiatry, Center for Medical Genetics and Molecular Medicine, Haukeland University Hospital, Bergen, Norway.
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authors.affiliation: Division of Psychiatry Research, Zucker Hillside Hospital, Glen Oaks, NY, USA.|Center for Psychiatric Neuroscience, Feinstein Institute for Medical Research, Manhasset, NY, USA.|Department of Psychiatry, Hofstra Northwell School of Medicine, Hempstead, NY, USA.
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authors.affiliation: Division of Psychiatry Research, Zucker Hillside Hospital, Glen Oaks, NY, USA.|Center for Psychiatric Neuroscience, Feinstein Institute for Medical Research, Manhasset, NY, USA.|Department of Psychiatry, Hofstra Northwell School of Medicine, Hempstead, NY, USA.
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mesh_terms: D000328:Adult; D000483:Alleles; D003071:Cognition / Q000502:physiology*; D005260:Female; D005787:Gene Frequency / Q000235:genetics; D056726:Genetic Association Studies / Q000379:methods; D056426:Genetic Loci / Q000235:genetics; D020022:Genetic Predisposition to Disease / Q000235:genetics; D014644:Genetic Variation / Q000235:genetics; D055106:Genome-Wide Association Study / Q000379:methods; D006801:Humans; D008297:Male; D008875:Middle Aged; D020412:Multifactorial Inheritance / Q000235:genetics; D019965:Neurocognitive Disorders / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D044465:White People / Q000235:genetics