Within-family studies for Mendelian randomization: avoiding dynastic, assortative mating, and population stratification biases
Fernando Pires Hartwig,
Gunnhild Åberge Vie,
Laura D Howe,
Dorret I. Boomsma,
Alexandra S. Havdahl,
Michael C. Neale,
Michel G. Nivard,
Nancy L Pedersen,
Chandra A. Reynolds,
Elliot M Tucker-Drob,
Tim T Morris,
MR within-family Consortium,
Johan Håkon Bjørngaard,
Cristen J. Willer,
David M. Evans,
Bjørn Olav Åsvol,
George Davey Smith,
Bjørn Olav Åsvold,
Neil M Davies
Posted 09 Apr 2019
bioRxiv DOI: 10.1101/602516
Posted 09 Apr 2019
Mendelian randomization (MR) is a widely-used method for causal inference using genetic data. Mendelian randomization studies of unrelated individuals may be susceptible to bias from family structure, for example, through dynastic effects which occur when parental genotypes directly affect offspring phenotypes. Here we describe methods for within-family Mendelian randomization and through simulations show that family-based methods can overcome bias due to dynastic effects. We illustrate these issues empirically using data from 61,008 siblings from the UK Biobank and Nord-Trøndelag Health Study. Both within-family and population-based Mendelian randomization analyses reproduced established effects of lower BMI reducing risk of diabetes and high blood pressure. However, while MR estimates from population-based samples of unrelated individuals suggested that taller height and lower BMI increase educational attainment, these effects largely disappeared in within-family MR analyses. We found differences between population-based and within-family based estimates, indicating the importance of controlling for family effects and population structure in Mendelian randomization studies.
- Downloaded 1,773 times
- Download rankings, all-time:
- Site-wide: 4,488 out of 89,581
- In genetics: 327 out of 4,628
- Year to date:
- Site-wide: 3,022 out of 89,581
- Since beginning of last month:
- Site-wide: 7,158 out of 89,581
Downloads over time
Distribution of downloads per paper, site-wide
- 18 Dec 2019: We're pleased to announce PanLingua, a new tool that enables you to search for machine-translated bioRxiv preprints using more than 100 different languages.
- 21 May 2019: PLOS Biology has published a community page about Rxivist.org and its design.
- 10 May 2019: The paper analyzing the Rxivist dataset has been published at eLife.
- 1 Mar 2019: We now have summary statistics about bioRxiv downloads and submissions.
- 8 Feb 2019: Data from Altmetric is now available on the Rxivist details page for every preprint. Look for the "donut" under the download metrics.
- 30 Jan 2019: preLights has featured the Rxivist preprint and written about our findings.
- 22 Jan 2019: Nature just published an article about Rxivist and our data.
- 13 Jan 2019: The Rxivist preprint is live!