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

Abstract

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 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. 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.

Genetic and Environmental Factors Underlying Parallel Changes in Body Mass Index and Alcohol Consumption: A 36-Year Longitudinal Study of Adult Twins

“…2. The use of covariates for additional exploratory purposes was considered [38][39][40] (online suppl. Table S1, S2; for all online suppl.…”

Associations of education attainment with gestational diabetes mellitus and the mediating effects of obesity: A Mendelian randomization study

“…Moreover, among individuals with college degrees, those with a higher education polygenic score exhibited a lower likelihood of obesity than those with a relatively lower education polygenic score. Howe et al [ 28 ] conducted a within-sibship MR study that revealed a strong association between higher EA and lower BMI. Furthermore, in an observational study, Panchal et al [ 29 ] found that individuals with lower EA (less than college graduates) had higher BMI than those with higher EA (college graduates and post-college degrees) [31.8 ± 6.4 vs. 29.6 ± 4.8 vs. 29.7 ± 5.2, p = 0.04].…”

Genetic evidence for T-wave area from 12-lead electrocardiograms to monitor cardiovascular diseases in patients taking diabetes medications

“…MRlap(23) was employed to correct the sample overlap and is a method to approximate the sample overlap using cross-trait LD-score regression (LDSC). It has been used in many studies for MR analysis(24, 25, 26, 27, 28). The detailed descriptions of all the MR approaches are given in the Supplementary Material.…”