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Genome-wide analyses of behavioural traits are subject to bias by misreports and longitudinal changes

Genome-wide association studies (GWAS) have discovered numerous genetic variants associated with human behavioural traits. However, behavioural traits are subject to misreports and longitudinal changes (MLC) which can cause biases in GWAS and follow-up analyses. Here, we demonstrate that individuals...

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Autores principales: Xue, Angli, Jiang, Longda, Zhu, Zhihong, Wray, Naomi R., Visscher, Peter M., Zeng, Jian, Yang, Jian
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7804181/
https://www.ncbi.nlm.nih.gov/pubmed/33436567
http://dx.doi.org/10.1038/s41467-020-20237-6
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author Xue, Angli
Jiang, Longda
Zhu, Zhihong
Wray, Naomi R.
Visscher, Peter M.
Zeng, Jian
Yang, Jian
author_facet Xue, Angli
Jiang, Longda
Zhu, Zhihong
Wray, Naomi R.
Visscher, Peter M.
Zeng, Jian
Yang, Jian
author_sort Xue, Angli
collection PubMed
description Genome-wide association studies (GWAS) have discovered numerous genetic variants associated with human behavioural traits. However, behavioural traits are subject to misreports and longitudinal changes (MLC) which can cause biases in GWAS and follow-up analyses. Here, we demonstrate that individuals with higher disease burden in the UK Biobank (n = 455,607) are more likely to misreport or reduce their alcohol consumption levels, and propose a correction procedure to mitigate the MLC-induced biases. The alcohol consumption GWAS signals removed by the MLC corrections are enriched in metabolic/cardiovascular traits. Almost all the previously reported negative estimates of genetic correlations between alcohol consumption and common diseases become positive/non-significant after the MLC corrections. We also observe MLC biases for smoking and physical activities in the UK Biobank. Our findings provide a plausible explanation of the controversy about the effects of alcohol consumption on health outcomes and a caution for future analyses of self-reported behavioural traits in biobank data.
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spelling pubmed-78041812021-01-21 Genome-wide analyses of behavioural traits are subject to bias by misreports and longitudinal changes Xue, Angli Jiang, Longda Zhu, Zhihong Wray, Naomi R. Visscher, Peter M. Zeng, Jian Yang, Jian Nat Commun Article Genome-wide association studies (GWAS) have discovered numerous genetic variants associated with human behavioural traits. However, behavioural traits are subject to misreports and longitudinal changes (MLC) which can cause biases in GWAS and follow-up analyses. Here, we demonstrate that individuals with higher disease burden in the UK Biobank (n = 455,607) are more likely to misreport or reduce their alcohol consumption levels, and propose a correction procedure to mitigate the MLC-induced biases. The alcohol consumption GWAS signals removed by the MLC corrections are enriched in metabolic/cardiovascular traits. Almost all the previously reported negative estimates of genetic correlations between alcohol consumption and common diseases become positive/non-significant after the MLC corrections. We also observe MLC biases for smoking and physical activities in the UK Biobank. Our findings provide a plausible explanation of the controversy about the effects of alcohol consumption on health outcomes and a caution for future analyses of self-reported behavioural traits in biobank data. Nature Publishing Group UK 2021-01-07 /pmc/articles/PMC7804181/ /pubmed/33436567 http://dx.doi.org/10.1038/s41467-020-20237-6 Text en © The Author(s) 2021 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
Xue, Angli
Jiang, Longda
Zhu, Zhihong
Wray, Naomi R.
Visscher, Peter M.
Zeng, Jian
Yang, Jian
Genome-wide analyses of behavioural traits are subject to bias by misreports and longitudinal changes
title Genome-wide analyses of behavioural traits are subject to bias by misreports and longitudinal changes
title_full Genome-wide analyses of behavioural traits are subject to bias by misreports and longitudinal changes
title_fullStr Genome-wide analyses of behavioural traits are subject to bias by misreports and longitudinal changes
title_full_unstemmed Genome-wide analyses of behavioural traits are subject to bias by misreports and longitudinal changes
title_short Genome-wide analyses of behavioural traits are subject to bias by misreports and longitudinal changes
title_sort genome-wide analyses of behavioural traits are subject to bias by misreports and longitudinal changes
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7804181/
https://www.ncbi.nlm.nih.gov/pubmed/33436567
http://dx.doi.org/10.1038/s41467-020-20237-6
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