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Cited by 135Genetic Associations and EpidemiologyCognitive Abilities and TestingIntergenerational and Educational Inequality Studies

The DOI matches its Crossref record; 66 of the 66 references it cites were found in a registry or an index.

Multivariable two-sample Mendelian randomization estimates of the effects of intelligence and education on health

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Davies, Neil Martin, Hill, W David, Anderson, Emma L, Sanderson, Eleanor, Deary, Ian J, Davey Smith, George·2019·eLife
DOI 10.7554/elife.43990PMC PMC6748790
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Abstract

Intelligence and education are predictive of better physical and mental health, socioeconomic position (SEP), and longevity. However, these associations are insufficient to prove that intelligence and/or education cause these outcomes. Intelligence and education are phenotypically and genetically correlated, which makes it difficult to elucidate causal relationships. We used univariate and multivariable Mendelian randomization to estimate the total and direct effects of intelligence and educational attainment on mental and physical health, measures of socioeconomic position, and longevity. Both intelligence and education had beneficial total effects. Higher intelligence had positive direct effects on income and alcohol consumption, and negative direct effects on moderate and vigorous physical activity. Higher educational attainment had positive direct effects on income, alcohol consumption, and vigorous physical activity, and negative direct effects on smoking, BMI and sedentary behaviour. If the Mendelian randomization assumptions hold, these findings suggest that both intelligence and education affect health.

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Figure 1. Possible explanations for associations of SNPs and intelligence, education and outcomes later in life. (A) Vertical pleiotropy: SNPs associated with intelligence and educational attainment could be vertically pleiotropic. This could occur if all of the effect of the SNPs on the outcomes is mediated via their effects on intelligence, the effect of intelligence on educational attainment, and the effect of educational attainment on the outcome. Confounders omitted from this figure for clarity. (B) Horizontal pleiotropy: The SNPs could be associated with the outcome via intelligence and educational attainment because of horizontal pleiotropy. This would occur if the SNPs had effects on the outcome via intelligence or education that were not mediated via the other trait. (C) Confounding pleiotropy: The SNPs could be associated with the outcomes, intelligence and educational attainment because of the effect of the SNPs on intelligence, and hence education, but that education had no direct effect on the outcome (i.e. the effects of the SNPs were entirely mediated via intelligence. This would occur if the SNPs had effects on the outcome via intelligence or education that were not mediated via the other trait (or vice versa). Multivariable Mendelian randomization does not overcome bias due to other pleiotropic effects by pathways other than intelligence or education.
Figure 1. Possible explanations for associations of SNPs and intelligence, education and outcomes later in life. (A) Vertical pleiotropy: SNPs associated with intelligence and educational attainment could be vertically pleiotropic. This could occur if all of the effect of the SNPs on the outcomes is mediated via their effects on intelligence, the effect of intelligence on educational attainment, and the effect of educational attainment on the outcome. Confounders omitted from this figure for clarity. (B) Horizontal pleiotropy: The SNPs could be associated with the outcome via intelligence and educational attainment because of horizontal pleiotropy. This would occur if the SNPs had effects on the outcome via intelligence or education that were not mediated via the other trait. (C) Confounding pleiotropy: The SNPs could be associated with the outcomes, intelligence and educational attainment because of the effect of the SNPs on intelligence, and hence education, but that education had no direct effect on the outcome (i.e. the effects of the SNPs were entirely mediated via intelligence. This would occur if the SNPs had effects on the outcome via intelligence or education that were not mediated via the other trait (or vice versa). Multivariable Mendelian randomization does not overcome bias due to other pleiotropic effects by pathways other than intelligence or education.CC BY · PubMed Central
Figure 2. Multivariable Mendelian randomization estimates the direct effect of intelligence and education on the outcomes. The direct effect (red arrow) excludes any effect of either intelligence (or education) that is mediated via education (intelligence) on the outcome. It requires genetic variation that explains a sufficient proportion of the variation in intelligence and education conditional on the other trait (Davey Smith and Hemani, 2014). It uses a set of SNPs that associate with intelligence and/or education at p<5×10−08.
Figure 2. Multivariable Mendelian randomization estimates the direct effect of intelligence and education on the outcomes. The direct effect (red arrow) excludes any effect of either intelligence (or education) that is mediated via education (intelligence) on the outcome. It requires genetic variation that explains a sufficient proportion of the variation in intelligence and education conditional on the other trait (Davey Smith and Hemani, 2014). It uses a set of SNPs that associate with intelligence and/or education at p<5×10−08.CC BY · PubMed Central
Figure 3. The bidirectional effects of SD differences in years of education and intelligence in UK Biobank. The error bars indicate 95% confidence intervals around the estimated phenotype-SNP associations. Two sample multivariable Mendelian randomization using results from Hill et al. (2019), Okbay et al. (2016) and UK Biobank data. These results suggest that intelligence increases length of schooling and that higher education leads to higher intelligence. Pleiotropy robust methods, such as MR-Egger suggested little bias in the IVW estimates of the effect of intelligence on education, but that the IVW results may substantially overestimate the effect of education on intelligence. Estimates adjusted for month of birth, year of birth, sex, interaction of sex and year of birth and the first 40 principal components. For panel A, Q-stat = 368.7 (p<0.0001), I2gx=34.7%. For panel B, Q = 183.3 (p<0.0001), I2gx=12.5%.
Figure 3. The bidirectional effects of SD differences in years of education and intelligence in UK Biobank. The error bars indicate 95% confidence intervals around the estimated phenotype-SNP associations. Two sample multivariable Mendelian randomization using results from Hill et al. (2019), Okbay et al. (2016) and UK Biobank data. These results suggest that intelligence increases length of schooling and that higher education leads to higher intelligence. Pleiotropy robust methods, such as MR-Egger suggested little bias in the IVW estimates of the effect of intelligence on education, but that the IVW results may substantially overestimate the effect of education on intelligence. Estimates adjusted for month of birth, year of birth, sex, interaction of sex and year of birth and the first 40 principal components. For panel A, Q-stat = 368.7 (p<0.0001), I2gx=34.7%. For panel B, Q = 183.3 (p<0.0001), I2gx=12.5%.CC BY · PubMed Central
Figure 4. The direct effects of SD changes in years of education and intelligence on later outcomes in UK Biobank. The error bars indicate 95% confidence intervals around the estimated effects. Estimated using two sample multivariable Mendelian randomization. Higher intelligence had direct effects on higher household income and alcohol consumption and less moderate and vigorous physical activity. Higher education had direct effects on decreased smoking, BMI, and sedentary behaviour and increased household income and rates of vigorous physical activity. These are estimates of the direct effects of intelligence (education) that are not mediated via education (intelligence).
Figure 4. The direct effects of SD changes in years of education and intelligence on later outcomes in UK Biobank. The error bars indicate 95% confidence intervals around the estimated effects. Estimated using two sample multivariable Mendelian randomization. Higher intelligence had direct effects on higher household income and alcohol consumption and less moderate and vigorous physical activity. Higher education had direct effects on decreased smoking, BMI, and sedentary behaviour and increased household income and rates of vigorous physical activity. These are estimates of the direct effects of intelligence (education) that are not mediated via education (intelligence).CC BY · PubMed Central

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Metadata

Authors
Davies, N. M., Hill, W. D., Anderson, E. L., Sanderson, E., Deary, I. J., & Davey Smith, G.
Affiliations
  • University of Bristol (GB)
  • University of Edinburgh (GB)
  • Medical Research Council Integrative Epidemiology Unit, University of Bristol, Bristol, United Kingdom
Corresponding author
Davies, Neil Martin
ORCID
Venue
eLife
Publisher
eLife Sciences Publications, Ltd
Published
2019-09-17
Volume
8
ISSN
2050-084X (ISSN-L)
DOI
10.7554/elife.43990
PMC
PMC6748790
OpenAlex
W2974720922
Cited by
135
References
66
Citations by year
2026: 6 · 2025: 19 · 2024: 26 · 2023: 33 · 2022: 18 · 2021: 17 · 2020: 12 · 2019: 4
FWCI
7.68
Type
journal article
Language
en
Open access
Licence
Locations
  • eLife (publishedVersion, cc-by)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
  • Edinburgh Research Explorer (University of Edinburgh) (submittedVersion, cc-by)
  • Bristol Research (University of Bristol) (submittedVersion, cc-by)
Funders
  • Economic and Social Research Council (ES/N000757/1)
  • Medical Research Council (MC_UU_12013/1, MC_UU_12013/9, MC_UU_00011/1, MR/K026992/1)
  • Age UK (Disconnected Mind Grant)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
  • Social Sciences › Psychology › Experimental and Cognitive Psychology › Cognitive Abilities and Testing
  • Social Sciences › Sociology and Political Science › Intergenerational and Educational Inequality Studies
Keywords
intelligence, educational attainment, mental health, physical health, socioeconomic position, longevity, income, alcohol consumption, physical activity, smoking, body mass index, sedentary behavior, genetic correlation
MeSH terms
Adult, Aged, Education, Female, United Kingdom, Health, Humans, Intelligence, Health Knowledge, Attitudes, Practice, Male, Middle Aged, Biostatistics

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