Educational attainment, health outcomes and mortality: a within-sibship Mendelian randomization study

Howe, L. J., Rasheed, H., Jones, P. R., Boomsma, D. I., Evans, D. M., Giannelis, A., Hayward, C., Hopper, J. L., Hughes, A., Lahtinen, H., Li, S., Lind, P. A., Martin, N. G., Martikainen, P., Medland, S. E., Morris, T. T., Nivard, M. G., Pingault, J., Silventoinen, K., Smith, J. A., Willoughby, E. A., Wilson, J. F., Social Science Genetic Association Consortium within Family Consortium, Åsvold, B. O., Næss, Ø. E., Smith, G. D., Kaprio, J., Brumpton, B., Davies, N. M.
medRxiv preprints
35 pages.
originally posted on: 13 January 2022 (2022), unpublished
Open Access


Previous Mendelian randomization (MR) studies using population samples (population-MR) have provided evidence for beneficial effects of educational attainment on health outcomes in adulthood. However, estimates from these studies may have been susceptible to bias from population stratification, assortative mating and indirect genetic effects due to unadjusted parental genotypes. Mendelian randomization using genetic association estimates derived from within-sibship models (within-sibship MR) can avoid these potential biases because genetic differences between siblings are due to random segregation at meiosis. Applying both population and within-sibship MR, we estimated the effects of genetic liability to educational attainment on body mass index (BMI), cigarette smoking, systolic blood pressure (SBP) and all-cause mortality. MR analyses used individual-level data on 72,932 siblings from UK Biobank and the Norwegian HUNT study and summary-level data from a within-sibship Genome-wide Association Study including over 140,000 individuals. Both population and within-sibship MR estimates provided evidence that educational attainment influences BMI, cigarette smoking and SBP. Genetic variantoutcome associations attenuated in the within-sibship model, but genetic varianteducational attainment associations also attenuated to a similar extent. Thus, withinsibship and population MR estimates were largely consistent. The within-sibship MR estimate of education on mortality was imprecise but consistent with a putative effect. These results provide evidence of beneficial individual-level effects of education (or liability to education) on adulthood health, independent of potential demographic and family-level confounders.

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