Avoiding dynastic, assortative mating, and population stratification biases in Mendelian randomization through within-family analyses. Journal Article uri icon



  • Estimates from Mendelian randomization studies of unrelated individuals can be biased due to uncontrolled confounding from familial effects. Here we describe methods for within-family Mendelian randomization analyses and use simulation studies to show that family-based analyses can reduce such biases. We illustrate empirically how familial effects can affect estimates using data from 61,008 siblings from the Nord-Trøndelag Health Study and UK Biobank and replicated our findings using 222,368 siblings from 23andMe. Both Mendelian randomization estimates using unrelated individuals and within family methods reproduced established effects of lower BMI reducing risk of diabetes and high blood pressure. However, while Mendelian randomization estimates from samples of unrelated individuals suggested that taller height and lower BMI increase educational attainment, these effects were strongly attenuated in within-family Mendelian randomization analyses. Our findings indicate the necessity of controlling for population structure and familial effects in Mendelian randomization studies.

publication date

  • July 14, 2020

has subject area

has restriction

  • gold

Date in CU Experts

  • January 23, 2022 6:21 AM

Full Author List

  • Brumpton B; Sanderson E; Heilbron K; Hartwig FP; Harrison S; Vie GÅ; Cho Y; Howe LD; Hughes A; Boomsma DI

author count

  • 35

Other Profiles

Electronic International Standard Serial Number (EISSN)

  • 2041-1723

Additional Document Info

start page

  • 3519


  • 11


  • 1