Mendelian randomisation analysis of the effect of educational attainment and cognitive ability on smoking behaviour

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Abstract

Recent analyses have shown educational attainment to be associated with a number of health outcomes. This association may, in part, be due to an effect of educational attainment on smoking behaviour. In this study, we apply a multivariable Mendelian randomisation design to determine whether the effect of educational attainment on smoking behaviour is due to educational attainment or general cognitive ability. We use individual data from the UK Biobank study ( N = 120,050) and summary data from large GWA studies of educational attainment, cognitive ability and smoking behaviour. Our results show that more years of education are associated with a reduced likelihood of smoking that is not due to an effect of general cognitive ability on smoking behaviour. Given the considerable physical harms associated with smoking, the effect of educational attainment on smoking is likely to contribute to the health inequalities associated with differences in educational attainment.

Abstract

Higher educational attainment is positively associated with a number of health outcomes. Here, Sanderson et al. use multivariable Mendelian randomisation analysis to test whether the association of educational attainment with smoking behaviour is direct or indirectly mediated via general cognitive ability.

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Evaluating the potential role of pleiotropy in Mendelian randomization studies

Gibran Hemani, Jack Bowden, George Davey Smith (2018)

Abstract Pleiotropy, the phenomenon of a single genetic variant influencing multiple traits, is likely widespread in the human genome. If pleiotropy arises because the single nucleotide polymorphism (SNP) influences one trait, which in turn influences another (‘vertical pleiotropy’), then Mendelian randomization (MR) can be used to estimate the causal influence between the traits. Of prime focus among the many limitations to MR is the unprovable assumption that apparent pleiotropic associations are mediated by the exposure (i.e. reflect vertical pleiotropy), and do not arise due to SNPs influencing the two traits through independent pathways (‘horizontal pleiotropy’). The burgeoning treasure trove of genetic associations yielded through genome wide association studies makes for a tantalizing prospect of phenome-wide causal inference. Recent years have seen substantial attention devoted to the problem of horizontal pleiotropy, and in this review we outline how newly developed methods can be used together to improve the reliability of MR.

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The nature of nurture: Effects of parental genotypes

Augustine Kong, Gudmar Thorleifsson, Michael L. Frigge … (2018)

Sequence variants in the parental genomes that are not transmitted to a child (the proband) are often ignored in genetic studies. Here we show that nontransmitted alleles can affect a child through their impacts on the parents and other relatives, a phenomenon we call "genetic nurture." Using results from a meta-analysis of educational attainment, we find that the polygenic score computed for the nontransmitted alleles of 21,637 probands with at least one parent genotyped has an estimated effect on the educational attainment of the proband that is 29.9% (P = 1.6 × 10-14) of that of the transmitted polygenic score. Genetic nurturing effects of this polygenic score extend to other traits. Paternal and maternal polygenic scores have similar effects on educational attainment, but mothers contribute more than fathers to nutrition- and heath-related traits.

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The neuroscience of human intelligence differences.

Ian Deary, Lars Penke, Wendy Johnson (2010)

Neuroscience is contributing to an understanding of the biological bases of human intelligence differences. This work is principally being conducted along two empirical fronts: genetics--quantitative and molecular--and brain imaging. Quantitative genetic studies have established that there are additive genetic contributions to different aspects of cognitive ability--especially general intelligence--and how they change through the lifespan. Molecular genetic studies have yet to identify reliably reproducible contributions from individual genes. Structural and functional brain-imaging studies have identified differences in brain pathways, especially parieto-frontal pathways, that contribute to intelligence differences. There is also evidence that brain efficiency correlates positively with intelligence.

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Author and article information

Contributors

Eleanor Sanderson:

ORCID: http://orcid.org/0000-0001-5188-5775

eleanor.sanderson@bristol.ac.uk

Journal

Journal ID (nlm-ta): Nat Commun

Journal ID (iso-abbrev): Nat Commun

Title: Nature Communications

Publisher: Nature Publishing Group UK (London )

ISSN (Electronic): 2041-1723

Publication date (Electronic): 3 July 2019

Publication date PMC-release: 3 July 2019

Publication date Collection: 2019

Volume: 10

Electronic Location Identifier: 2949

Affiliations

[1 ]ISNI 0000 0004 1936 7603, GRID grid.5337.2, MRC Integrative Epidemiology Unit at the University of Bristol, ; Bristol, BS8 2BN UK

[2 ]ISNI 0000 0004 1936 7603, GRID grid.5337.2, Population Health Sciences, Bristol Medical School, , University of Bristol, ; Bristol, BS8 2BN UK

[3 ]ISNI 0000 0004 1936 7603, GRID grid.5337.2, UK Centre for Tobacco and Alcohol Studies, School of Experimental Psychology, , University of Bristol, ; Bristol, BS8 1TU UK

Author information

Eleanor Sanderson http://orcid.org/0000-0001-5188-5775

George Davey Smith http://orcid.org/0000-0002-1407-8314

Marcus R. Munafò http://orcid.org/0000-0002-4049-993X

Article

Publisher ID: 10679

DOI: 10.1038/s41467-019-10679-y

PMC ID: 6610141

PubMed ID: 31270314

SO-VID: ab229b35-a3ff-48dc-9705-c54ab4149541

License:

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/.

History

Date received : 6 July 2018

Date accepted : 7 May 2019

Funding

Funded by: FundRef https://doi.org/10.13039/501100000265, RCUK | Medical Research Council (MRC);

Award ID: MM_UU_00011/1

Award ID: MM_UU_00011/2

Award ID: MM_UU_00011/1

Award ID: MM_UU_00011/2

Award Recipient : Eleanor Sanderson George Davey Smith Jack Bowden

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ScienceOpen disciplines: Uncategorized

Keywords: genome-wide association studies,epidemiology,education,human behaviour

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ScienceOpen disciplines: Uncategorized

Keywords: genome-wide association studies, epidemiology, education, human behaviour

Mendelian randomisation analysis of the effect of educational attainment and cognitive ability on smoking behaviour

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Asian Journal of Environment-Behaviour Studies (ajE-Bs)

Most cited references 22

Evaluating the potential role of pleiotropy in Mendelian randomization studies

The nature of nurture: Effects of parental genotypes

The neuroscience of human intelligence differences.

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