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Genomic analysis of family data reveals additional genetic effects on intelligence and personality

W. David Hill, Ruben C. Arslan, Charley Xia, Michelle Luciano, Carmen Amador, Pau Navarro, Caroline Hayward, Reka Nagy, David J. Porteous, Andrew M. McIntosh, Ian J. Deary, Chris S. Haley, Lars Penke
doi: https://doi.org/10.1101/106203
W. David Hill
1Centre for Cognitive Ageing and Cognitive Epidemiology, University of Edinburgh, 7 George Square, Edinburgh EH8 9JZ, UK
2Department of Psychology, University of Edinburgh, 7 George Square, Edinburgh EH8 9JZ, UK
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Ruben C. Arslan
3Georg Elias Müller Institute of Psychology, Georg August University Göttingen, Germany
4Leibniz ScienceCampus Primate Cognition, Göttingen Germany
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Charley Xia
5MRC Human Genetics Unit, Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, UK
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Michelle Luciano
1Centre for Cognitive Ageing and Cognitive Epidemiology, University of Edinburgh, 7 George Square, Edinburgh EH8 9JZ, UK
2Department of Psychology, University of Edinburgh, 7 George Square, Edinburgh EH8 9JZ, UK
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Carmen Amador
5MRC Human Genetics Unit, Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, UK
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Pau Navarro
5MRC Human Genetics Unit, Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, UK
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Caroline Hayward
5MRC Human Genetics Unit, Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, UK
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Reka Nagy
5MRC Human Genetics Unit, Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, UK
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David J. Porteous
1Centre for Cognitive Ageing and Cognitive Epidemiology, University of Edinburgh, 7 George Square, Edinburgh EH8 9JZ, UK
6Generation Scotland, Centre for Genomic and Experimental Medicine, Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh EH4 2XU, UK
8Medical Genetics Section, Centre for Genomic and Experimental Medicine, Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh
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Andrew M. McIntosh
1Centre for Cognitive Ageing and Cognitive Epidemiology, University of Edinburgh, 7 George Square, Edinburgh EH8 9JZ, UK
9Division of Psychiatry, University of Edinburgh, Royal Edinburgh Hospital, Edinburgh EH10 5HF
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Ian J. Deary
1Centre for Cognitive Ageing and Cognitive Epidemiology, University of Edinburgh, 7 George Square, Edinburgh EH8 9JZ, UK
2Department of Psychology, University of Edinburgh, 7 George Square, Edinburgh EH8 9JZ, UK
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Chris S. Haley
5MRC Human Genetics Unit, Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, UK
10The Roslin Institute and Royal (Dick) School of Veterinary Sciences, University of Edinburgh, UK
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Lars Penke
1Centre for Cognitive Ageing and Cognitive Epidemiology, University of Edinburgh, 7 George Square, Edinburgh EH8 9JZ, UK
3Georg Elias Müller Institute of Psychology, Georg August University Göttingen, Germany
4Leibniz ScienceCampus Primate Cognition, Göttingen Germany
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Abstract

Pedigree-based analyses of intelligence have reported that genetic differences account for 50-80% of the phenotypic variation. For personality traits, these effects are smaller with 34-48% of the variance being explained by genetic differences. However, molecular genetic studies using unrelated individuals typically report a heritability estimate of around 30% for intelligence and between 0% and 15% for personality variables. Pedigree-based estimates and molecular genetic estimates may differ because current genotyping platforms are poor at tagging causal variants, variants with low minor allele frequency, copy number variants, and structural variants. Using ~20 000 individuals in the Generation Scotland family cohort genotyped for ~520 000 single nucleotide polymorphisms (SNPs), we exploit the high levels of linkage disequilibrium (LD) found in members of the same family to quantify the total effect of genetic variants that are not tagged in GWASs of unrelated individuals. In our models, genetic variants in low LD with genotyped SNPs explain over half of the genetic variance in intelligence, education, and neuroticism. By capturing these additional genetic effects our models closely approximate the heritability estimates from twin studies for intelligence and education, but not for neuroticism and extraversion. From an evolutionary genetic perspective, a substantial contribution of genetic variants that are not common within the population to individual differences in intelligence, education, and neuroticism is consistent with mutation-selection balance.

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Posted February 06, 2017.
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Genomic analysis of family data reveals additional genetic effects on intelligence and personality
W. David Hill, Ruben C. Arslan, Charley Xia, Michelle Luciano, Carmen Amador, Pau Navarro, Caroline Hayward, Reka Nagy, David J. Porteous, Andrew M. McIntosh, Ian J. Deary, Chris S. Haley, Lars Penke
bioRxiv 106203; doi: https://doi.org/10.1101/106203
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Genomic analysis of family data reveals additional genetic effects on intelligence and personality
W. David Hill, Ruben C. Arslan, Charley Xia, Michelle Luciano, Carmen Amador, Pau Navarro, Caroline Hayward, Reka Nagy, David J. Porteous, Andrew M. McIntosh, Ian J. Deary, Chris S. Haley, Lars Penke
bioRxiv 106203; doi: https://doi.org/10.1101/106203

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