Avoiding dynastic, assortative mating, and population stratification biases in Mendelian randomization through within-family analyses

Author:

Brumpton BenORCID,Sanderson EleanorORCID,Heilbron Karl,Hartwig Fernando PiresORCID,Harrison SeanORCID,Vie Gunnhild ÅbergeORCID,Cho YoonsuORCID,Howe Laura D.,Hughes Amanda,Boomsma Dorret I.,Havdahl AlexandraORCID,Hopper John,Neale MichaelORCID,Nivard Michel G.ORCID,Pedersen Nancy L.,Reynolds Chandra A.,Tucker-Drob Elliot M.,Grotzinger AndrewORCID,Howe Laurence,Morris TimORCID,Li Shuai,Brumpton Ben,Sanderson Eleanor,Heilbron Karl,Hartwig Fernando Pires,Harrison Sean,Vie Gunnhild Åberge,Cho Yoonsu,Howe Laura D.,Hughes Amanda,Boomsma Dorret I.,Havdahl Alexandra,Hopper John,Neale Michael,Nivard Michel G.,Pedersen Nancy L.,Reynolds Chandra A.,Tucker-Drob Elliot M.,Grotzinger Andrew,Howe Laurence,Morris Tim,Li Shuai,Auton Adam,Windmeijer Frank,Chen Wei-Min,Bjørngaard Johan Håkon,Hveem Kristian,Willer Cristen,Evans David M.,Kaprio Jaakko,Smith George Davey,Åsvold Bjørn Olav,Hemani Gibran,Davies Neil M.,Heilbron Karl,Auton Adam,Auton Adam,Windmeijer Frank,Chen Wei-Min,Bjørngaard Johan Håkon,Hveem Kristian,Willer CristenORCID,Evans David M.ORCID,Kaprio JaakkoORCID,Davey Smith GeorgeORCID,Åsvold Bjørn Olav,Hemani GibranORCID,Davies Neil M.ORCID, ,

Abstract

AbstractEstimates 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.

Publisher

Springer Science and Business Media LLC

Subject

General Physics and Astronomy,General Biochemistry, Genetics and Molecular Biology,General Chemistry

Cited by 235 articles. 订阅此论文施引文献 订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献

同舟云学术

1.学者识别学者识别

2.学术分析学术分析

3.人才评估人才评估

"同舟云学术"是以全球学者为主线,采集、加工和组织学术论文而形成的新型学术文献查询和分析系统,可以对全球学者进行文献检索和人才价值评估。用户可以通过关注某些学科领域的顶尖人物而持续追踪该领域的学科进展和研究前沿。经过近期的数据扩容,当前同舟云学术共收录了国内外主流学术期刊6万余种,收集的期刊论文及会议论文总量共计约1.5亿篇,并以每天添加12000余篇中外论文的速度递增。我们也可以为用户提供个性化、定制化的学者数据。欢迎来电咨询!咨询电话:010-8811{复制后删除}0370

www.globalauthorid.com

TOP

Copyright © 2019-2024 北京同舟云网络信息技术有限公司
京公网安备11010802033243号  京ICP备18003416号-3