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

Laurence J Howe; Humaira Rasheed; Paul R Jones; Dorret I Boomsma; David M Evans; Alexandros Giannelis; Caroline Hayward; John L Hopper; Amanda Hughes; Hannu Lahtinen; Shuai Li; Penelope A Lind; Nicholas G Martin; Pekka Martikainen; Sarah E Medland; Tim T Morris; Michel G Nivard; Jean-Baptiste Pingault; Karri Silventoinen; Jennifer A Smith; Emily A Willoughby; James F Wilson; Within Family Consortium (Christina C. Dahm, member); Bjørn Olav Åsvold; Øyvind E Næss; George Davey Smith; Jaakko Kaprio; Ben Brumpton; Neil M Davies; Christina C. Dahm

doi:10.1093/ije/dyad079

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

Laurence J Howe^*, Humaira Rasheed, Paul R Jones, Dorret I Boomsma, David M Evans, Alexandros Giannelis, Caroline Hayward, John L Hopper, Amanda Hughes, Hannu Lahtinen, Shuai Li, Penelope A Lind, Nicholas G Martin, Pekka Martikainen, Sarah E Medland, Tim T Morris, Michel G Nivard, Jean-Baptiste Pingault, Karri Silventoinen, Jennifer A SmithEmily A Willoughby, James F Wilson, Within Family Consortium (Christina C. Dahm, member), Bjørn Olav Åsvold, Øyvind E Næss, George Davey Smith, Jaakko Kaprio, Ben Brumpton, Neil M Davies, Christina C. Dahm (Member of author collaboration)

^*Corresponding author for this work

Department of Public Health - Department of Epidemiology

Research output: Contribution to journal/Conference contribution in journal/Contribution to newspaper › Journal article › Research › peer-review

10 Citations (Scopus)

Abstract

BACKGROUND: 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. MR 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.

METHODS: 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 >140 000 individuals.

RESULTS: Both population and within-sibship MR estimates provided evidence that educational attainment decreased BMI, cigarette smoking and SBP. Genetic variant-outcome associations attenuated in the within-sibship model, but genetic variant-educational attainment associations also attenuated to a similar extent. Thus, within-sibship and population MR estimates were largely consistent. The within-sibship MR estimate of education on mortality was imprecise but consistent with a putative effect.

CONCLUSIONS: These results provide evidence of beneficial individual-level effects of education (or liability to education) on adulthood health, independently of potential demographic and family-level confounders.

Original language	English
Journal	International Journal of Epidemiology
Volume	52
Issue	5
Pages (from-to)	1579–1591
Number of pages	13
ISSN	0300-5771
DOIs	https://doi.org/10.1093/ije/dyad079
Publication status	Published - Oct 2023

Keywords

Mendelian randomization
Within-sibship
educational attainment
mortality

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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.-B., Silventoinen, K., ... Dahm, C. C. (2023). Educational attainment, health outcomes and mortality: a within-sibship Mendelian randomization study. International Journal of Epidemiology, 52(5), 1579–1591. https://doi.org/10.1093/ije/dyad079

@article{c09ff04a5ebb458c81a3d155e9927512,

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

abstract = "BACKGROUND: 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. MR 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.METHODS: 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 >140 000 individuals.RESULTS: Both population and within-sibship MR estimates provided evidence that educational attainment decreased BMI, cigarette smoking and SBP. Genetic variant-outcome associations attenuated in the within-sibship model, but genetic variant-educational attainment associations also attenuated to a similar extent. Thus, within-sibship and population MR estimates were largely consistent. The within-sibship MR estimate of education on mortality was imprecise but consistent with a putative effect.CONCLUSIONS: These results provide evidence of beneficial individual-level effects of education (or liability to education) on adulthood health, independently of potential demographic and family-level confounders.",

keywords = "Mendelian randomization, Within-sibship, educational attainment, mortality",

author = "Howe, {Laurence J} and Humaira Rasheed and Jones, {Paul R} and Boomsma, {Dorret I} and Evans, {David M} and Alexandros Giannelis and Caroline Hayward and Hopper, {John L} and Amanda Hughes and Hannu Lahtinen and Shuai Li and Lind, {Penelope A} and Martin, {Nicholas G} and Pekka Martikainen and Medland, {Sarah E} and Morris, {Tim T} and Nivard, {Michel G} and Jean-Baptiste Pingault and Karri Silventoinen and Smith, {Jennifer A} and Willoughby, {Emily A} and Wilson, {James F} and {Within Family Consortium (Christina C. Dahm, member)} and {\AA}svold, {Bj{\o}rn Olav} and N{\ae}ss, {{\O}yvind E} and {Davey Smith}, George and Jaakko Kaprio and Ben Brumpton and Davies, {Neil M} and Dahm, {Christina C.}",

note = "{\textcopyright} The Author(s) 2023. Published by Oxford University Press on behalf of the International Epidemiological Association.",

year = "2023",

month = oct,

doi = "10.1093/ije/dyad079",

language = "English",

volume = "52",

pages = "1579–1591",

journal = "International Journal of Epidemiology",

issn = "0300-5771",

publisher = "Oxford University Press",

number = "5",

}

Howe, LJ, Rasheed, H, Jones, PR, Boomsma, DI, Evans, DM, Giannelis, A, Hayward, C, Hopper, JL, Hughes, A, Lahtinen, H, Li, S, Lind, PA, Martin, NG, Martikainen, P, Medland, SE, Morris, TT, Nivard, MG, Pingault, J-B, Silventoinen, K, Smith, JA, Willoughby, EA, Wilson, JF, Within Family Consortium (Christina C. Dahm, member), Åsvold, BO, Næss, ØE, Davey Smith, G, Kaprio, J, Brumpton, B, Davies, NM & Dahm, CC 2023, 'Educational attainment, health outcomes and mortality: a within-sibship Mendelian randomization study', International Journal of Epidemiology, vol. 52, no. 5, pp. 1579–1591. https://doi.org/10.1093/ije/dyad079

Educational attainment, health outcomes and mortality: a within-sibship Mendelian randomization study. / Howe, Laurence J; Rasheed, Humaira; Jones, Paul R et al.
In: International Journal of Epidemiology, Vol. 52, No. 5, 10.2023, p. 1579–1591.

Research output: Contribution to journal/Conference contribution in journal/Contribution to newspaper › Journal article › Research › peer-review

TY - JOUR

T1 - Educational attainment, health outcomes and mortality

T2 - a within-sibship Mendelian randomization study

AU - Howe, Laurence J

AU - Rasheed, Humaira

AU - Jones, Paul R

AU - Boomsma, Dorret I

AU - Evans, David M

AU - Giannelis, Alexandros

AU - Hayward, Caroline

AU - Hopper, John L

AU - Hughes, Amanda

AU - Lahtinen, Hannu

AU - Li, Shuai

AU - Lind, Penelope A

AU - Martin, Nicholas G

AU - Martikainen, Pekka

AU - Medland, Sarah E

AU - Morris, Tim T

AU - Nivard, Michel G

AU - Pingault, Jean-Baptiste

AU - Silventoinen, Karri

AU - Smith, Jennifer A

AU - Willoughby, Emily A

AU - Wilson, James F

AU - Within Family Consortium (Christina C. Dahm, member)

AU - Åsvold, Bjørn Olav

AU - Næss, Øyvind E

AU - Davey Smith, George

AU - Kaprio, Jaakko

AU - Brumpton, Ben

AU - Davies, Neil M

AU - Dahm, Christina C.

N1 - © The Author(s) 2023. Published by Oxford University Press on behalf of the International Epidemiological Association.

PY - 2023/10

Y1 - 2023/10

N2 - BACKGROUND: 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. MR 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.METHODS: 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 >140 000 individuals.RESULTS: Both population and within-sibship MR estimates provided evidence that educational attainment decreased BMI, cigarette smoking and SBP. Genetic variant-outcome associations attenuated in the within-sibship model, but genetic variant-educational attainment associations also attenuated to a similar extent. Thus, within-sibship and population MR estimates were largely consistent. The within-sibship MR estimate of education on mortality was imprecise but consistent with a putative effect.CONCLUSIONS: These results provide evidence of beneficial individual-level effects of education (or liability to education) on adulthood health, independently of potential demographic and family-level confounders.

AB - BACKGROUND: 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. MR 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.METHODS: 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 >140 000 individuals.RESULTS: Both population and within-sibship MR estimates provided evidence that educational attainment decreased BMI, cigarette smoking and SBP. Genetic variant-outcome associations attenuated in the within-sibship model, but genetic variant-educational attainment associations also attenuated to a similar extent. Thus, within-sibship and population MR estimates were largely consistent. The within-sibship MR estimate of education on mortality was imprecise but consistent with a putative effect.CONCLUSIONS: These results provide evidence of beneficial individual-level effects of education (or liability to education) on adulthood health, independently of potential demographic and family-level confounders.

KW - Mendelian randomization

KW - Within-sibship

KW - educational attainment

KW - mortality

UR - http://www.scopus.com/inward/record.url?scp=85173847739&partnerID=8YFLogxK

U2 - 10.1093/ije/dyad079

DO - 10.1093/ije/dyad079

M3 - Journal article

C2 - 37295953

SN - 0300-5771

VL - 52

SP - 1579

EP - 1591

JO - International Journal of Epidemiology

JF - International Journal of Epidemiology

IS - 5

ER -

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

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