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A genome-wide association study for extremely high intelligence

We used a case–control genome-wide association (GWA) design with cases consisting of 1238 individuals from the top 0.0003 (~170 mean IQ) of the population distribution of intelligence and 8172 unselected population-based controls. The single-nucleotide polymorphism heritability for the extreme IQ tr...

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Autores principales: Zabaneh, D, Krapohl, E, Gaspar, H A, Curtis, C, Lee, S H, Patel, H, Newhouse, S, Wu, H M, Simpson, M A, Putallaz, M, Lubinski, D, Plomin, R, Breen, G
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5987166/
https://www.ncbi.nlm.nih.gov/pubmed/29731509
http://dx.doi.org/10.1038/mp.2017.121
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author Zabaneh, D
Krapohl, E
Gaspar, H A
Curtis, C
Lee, S H
Patel, H
Newhouse, S
Wu, H M
Simpson, M A
Putallaz, M
Lubinski, D
Plomin, R
Breen, G
author_facet Zabaneh, D
Krapohl, E
Gaspar, H A
Curtis, C
Lee, S H
Patel, H
Newhouse, S
Wu, H M
Simpson, M A
Putallaz, M
Lubinski, D
Plomin, R
Breen, G
author_sort Zabaneh, D
collection PubMed
description We used a case–control genome-wide association (GWA) design with cases consisting of 1238 individuals from the top 0.0003 (~170 mean IQ) of the population distribution of intelligence and 8172 unselected population-based controls. The single-nucleotide polymorphism heritability for the extreme IQ trait was 0.33 (0.02), which is the highest so far for a cognitive phenotype, and significant genome-wide genetic correlations of 0.78 were observed with educational attainment and 0.86 with population IQ. Three variants in locus ADAM12 achieved genome-wide significance, although they did not replicate with published GWA analyses of normal-range IQ or educational attainment. A genome-wide polygenic score constructed from the GWA results accounted for 1.6% of the variance of intelligence in the normal range in an unselected sample of 3414 individuals, which is comparable to the variance explained by GWA studies of intelligence with substantially larger sample sizes. The gene family plexins, members of which are mutated in several monogenic neurodevelopmental disorders, was significantly enriched for associations with high IQ. This study shows the utility of extreme trait selection for genetic study of intelligence and suggests that extremely high intelligence is continuous genetically with normal-range intelligence in the population.
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spelling pubmed-59871662018-06-06 A genome-wide association study for extremely high intelligence Zabaneh, D Krapohl, E Gaspar, H A Curtis, C Lee, S H Patel, H Newhouse, S Wu, H M Simpson, M A Putallaz, M Lubinski, D Plomin, R Breen, G Mol Psychiatry Original Article We used a case–control genome-wide association (GWA) design with cases consisting of 1238 individuals from the top 0.0003 (~170 mean IQ) of the population distribution of intelligence and 8172 unselected population-based controls. The single-nucleotide polymorphism heritability for the extreme IQ trait was 0.33 (0.02), which is the highest so far for a cognitive phenotype, and significant genome-wide genetic correlations of 0.78 were observed with educational attainment and 0.86 with population IQ. Three variants in locus ADAM12 achieved genome-wide significance, although they did not replicate with published GWA analyses of normal-range IQ or educational attainment. A genome-wide polygenic score constructed from the GWA results accounted for 1.6% of the variance of intelligence in the normal range in an unselected sample of 3414 individuals, which is comparable to the variance explained by GWA studies of intelligence with substantially larger sample sizes. The gene family plexins, members of which are mutated in several monogenic neurodevelopmental disorders, was significantly enriched for associations with high IQ. This study shows the utility of extreme trait selection for genetic study of intelligence and suggests that extremely high intelligence is continuous genetically with normal-range intelligence in the population. Nature Publishing Group 2018-05 2017-07-04 /pmc/articles/PMC5987166/ /pubmed/29731509 http://dx.doi.org/10.1038/mp.2017.121 Text en Copyright © 2018 The Author(s) http://creativecommons.org/licenses/by-nc-sa/4.0/ This work is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by-nc-sa/4.0/
spellingShingle Original Article
Zabaneh, D
Krapohl, E
Gaspar, H A
Curtis, C
Lee, S H
Patel, H
Newhouse, S
Wu, H M
Simpson, M A
Putallaz, M
Lubinski, D
Plomin, R
Breen, G
A genome-wide association study for extremely high intelligence
title A genome-wide association study for extremely high intelligence
title_full A genome-wide association study for extremely high intelligence
title_fullStr A genome-wide association study for extremely high intelligence
title_full_unstemmed A genome-wide association study for extremely high intelligence
title_short A genome-wide association study for extremely high intelligence
title_sort genome-wide association study for extremely high intelligence
topic Original Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5987166/
https://www.ncbi.nlm.nih.gov/pubmed/29731509
http://dx.doi.org/10.1038/mp.2017.121
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