| Title: |
Avoiding dynastic, assortative mating, and population stratification biases in Mendelian randomization through within-family analyses |
| Authors: |
Brumpton, Ben Michael; Sanderson, Eleanor; Heilbron, Karl; Hartwig, FP; Harrison, S; Vie, Gunnhild Åberge; Cho, Y; Howe, LD; Hughes, A; Boomsma, D; Havdahl, Alexandra; Hopper, J; Neale, M; Nivard, Michel G.; Pedersen, N; Reynolds, CA; Tucker-D, EM; Grotzinger, A; Howe, Laurence; Morris, Tim; Li, Shuai; Within-Family Consortium, The; 23andMe Research Team, The; Auton, A; Windmeijer, F; Chen, W-M; Bjørngaard, Johan Håkon; Hveem, Kristian; Willer, C; Evans, DM; Kaprio, J; Davey Smith, G; Åsvold, BO; Åsvold, Bjørn Olav; Hemani, G; Davies, Neil Martin |
| Source: |
11 ; Nature Communications ; 3519 |
| Publisher Information: |
Nature |
| Publication Year: |
2020 |
| Collection: |
Open archive Nord universitet |
| Subject Terms: |
VDP::Matematikk og Naturvitenskap: 400; VDP::Matematikk og Naturvitenskap: 400::Basale biofag: 470; VDP::Matematikk og Naturvitenskap: 400::Basale biofag: 470::Genetikk og genomikk: 474 |
| Description: |
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. ; publishedVersion |
| Document Type: |
article in journal/newspaper |
| File Description: |
application/pdf |
| Language: |
English |
| Relation: |
https://www.nature.com/articles/s41467-020-17117-4; Norges forskningsråd: 274611; Helse Sør-Øst RHF: 2018059; Stiftelsen Kristian Gerhard Jebsen: SKGJ-MED-015; Norges forskningsråd: 250335; Norges forskningsråd: 295989; Helse Sør-Øst RHF: 2020022.; https://hdl.handle.net/11250/2733878; cristin:1831060 |
| DOI: |
10.1038/s41467-020-17117-4 |
| Availability: |
https://hdl.handle.net/11250/2733878; https://doi.org/10.1038/s41467-020-17117-4 |
| Rights: |
Navngivelse 4.0 Internasjonal ; http://creativecommons.org/licenses/by/4.0/deed.no ; © 2020 The Author(s) |
| Accession Number: |
edsbas.30DEB4C3 |
| Database: |
BASE |