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Fine mapping genetic associations between the HLA region and extremely high intelligence
General cognitive ability (intelligence) is one of the most heritable behavioural traits and most predictive of socially important outcomes and health. We hypothesized that some of the missing heritability of IQ might lie hidden in the human leukocyte antigen (HLA) region, which plays a critical rol...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group
2017
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5259706/ https://www.ncbi.nlm.nih.gov/pubmed/28117369 http://dx.doi.org/10.1038/srep41182 |
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author | Zabaneh, Delilah Krapohl, Eva Simpson, Michael A. Miller, Mike B. Iacono, William G. McGue, Matt Putallaz, Martha Lubinski, David Plomin, Robert Breen, Gerome |
author_facet | Zabaneh, Delilah Krapohl, Eva Simpson, Michael A. Miller, Mike B. Iacono, William G. McGue, Matt Putallaz, Martha Lubinski, David Plomin, Robert Breen, Gerome |
author_sort | Zabaneh, Delilah |
collection | PubMed |
description | General cognitive ability (intelligence) is one of the most heritable behavioural traits and most predictive of socially important outcomes and health. We hypothesized that some of the missing heritability of IQ might lie hidden in the human leukocyte antigen (HLA) region, which plays a critical role in many diseases and traits but is not well tagged in conventional GWAS. Using a uniquely powered design, we investigated whether fine-mapping of the HLA region could narrow the missing heritability gap. Our case-control design included 1,393 cases with extremely high intelligence scores (top 0.0003 of the population equivalent to IQ > 147) and 3,253 unselected population controls. We imputed variants in 200 genes across the HLA region, one SNP (rs444921) reached our criterion for study-wide significance. SNP-based heritability of the HLA variants was small and not significant (h(2) = 0.3%, SE = 0.2%). A polygenic score from the case-control genetic association analysis of SNPs in the HLA region did not significantly predict individual differences in intelligence in an independent unselected sample. We conclude that although genetic variation in the HLA region is important to the aetiology of many disorders, it does not appear to be hiding much of the missing heritability of intelligence. |
format | Online Article Text |
id | pubmed-5259706 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | Nature Publishing Group |
record_format | MEDLINE/PubMed |
spelling | pubmed-52597062017-01-24 Fine mapping genetic associations between the HLA region and extremely high intelligence Zabaneh, Delilah Krapohl, Eva Simpson, Michael A. Miller, Mike B. Iacono, William G. McGue, Matt Putallaz, Martha Lubinski, David Plomin, Robert Breen, Gerome Sci Rep Article General cognitive ability (intelligence) is one of the most heritable behavioural traits and most predictive of socially important outcomes and health. We hypothesized that some of the missing heritability of IQ might lie hidden in the human leukocyte antigen (HLA) region, which plays a critical role in many diseases and traits but is not well tagged in conventional GWAS. Using a uniquely powered design, we investigated whether fine-mapping of the HLA region could narrow the missing heritability gap. Our case-control design included 1,393 cases with extremely high intelligence scores (top 0.0003 of the population equivalent to IQ > 147) and 3,253 unselected population controls. We imputed variants in 200 genes across the HLA region, one SNP (rs444921) reached our criterion for study-wide significance. SNP-based heritability of the HLA variants was small and not significant (h(2) = 0.3%, SE = 0.2%). A polygenic score from the case-control genetic association analysis of SNPs in the HLA region did not significantly predict individual differences in intelligence in an independent unselected sample. We conclude that although genetic variation in the HLA region is important to the aetiology of many disorders, it does not appear to be hiding much of the missing heritability of intelligence. Nature Publishing Group 2017-01-24 /pmc/articles/PMC5259706/ /pubmed/28117369 http://dx.doi.org/10.1038/srep41182 Text en Copyright © 2017, The Author(s) http://creativecommons.org/licenses/by/4.0/ This work is licensed under a Creative Commons Attribution 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/4.0/ |
spellingShingle | Article Zabaneh, Delilah Krapohl, Eva Simpson, Michael A. Miller, Mike B. Iacono, William G. McGue, Matt Putallaz, Martha Lubinski, David Plomin, Robert Breen, Gerome Fine mapping genetic associations between the HLA region and extremely high intelligence |
title | Fine mapping genetic associations between the HLA region and extremely high intelligence |
title_full | Fine mapping genetic associations between the HLA region and extremely high intelligence |
title_fullStr | Fine mapping genetic associations between the HLA region and extremely high intelligence |
title_full_unstemmed | Fine mapping genetic associations between the HLA region and extremely high intelligence |
title_short | Fine mapping genetic associations between the HLA region and extremely high intelligence |
title_sort | fine mapping genetic associations between the hla region and extremely high intelligence |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5259706/ https://www.ncbi.nlm.nih.gov/pubmed/28117369 http://dx.doi.org/10.1038/srep41182 |
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