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Avoiding dynastic, assortative mating, and population stratification biases in Mendelian randomization through within-family analyses
- Source :
- Nature Communications, Vol 11, Iss 1, Pp 1-13 (2020), Brumpton, B, Boomsma, D I, Neale, M, Nivard, M G, Davies, N M & The 23andMe Research Team 2020, ' Avoiding dynastic, assortative mating, and population stratification biases in Mendelian randomization through within-family analyses ', Nature Communications, vol. 11, no. 1, 3519, pp. 1-13 . https://doi.org/10.1038/s41467-020-17117-4, Nature Communications, Nature Communications, 11(1):3519, 1-13. Nature Publishing Group, Brumpton, B, Sanderson, E, Heilbron, K, Hartwig, F P, Harrison, S, Vie, G Å, Cho, Y, Howe, L D, Hughes, A, Boomsma, D I, Havdahl, A, Hopper, J L, Neale, M, Nivard, M G, Pedersen, N L, Reynolds, C, Tucker-Drob, E M, Howe, L, Morris, T, Lin, S, the 23 and Me Research Team, Auton, A, Windmeijer, F, Chen, W-M, Bjørngaard, J H, Hveem, K, Willer, C J, Evans, D M, Kaprio, J A, Davey Smith, G, Åsvold, B O & Hemani, G & Davies, N M 2020, ' Avoiding dynastic, assortative mating, and population stratification biases in Mendelian randomization through within-family analyses ', Nature Communications, vol. 11, 3519 (2020) . https://doi.org/10.1038/s41467-020-17117-4
- Publication Year :
- 2020
- Publisher :
- Nature Portfolio, 2020.
-
Abstract
- 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.<br />Family-based study designs have been applied to resolve confounding by population stratification, dynastic effects and assortative mating in genetic association analyses. Here, Brumpton et al. describe theory and simulations for overcoming such biases in Mendelian randomization through within-family studies.
- Subjects :
- 0301 basic medicine
Male
Netherlands Twin Register (NTR)
gene-environment correlation
Epidemiology
General Physics and Astronomy
Matematikk og Naturvitenskap: 400::Basale biofag: 470 [VDP]
Body Mass Index
0302 clinical medicine
HEIGHT
Risk Factors
Genetics research
genetics
030212 general & internal medicine
lcsh:Science
Multidisciplinary
Confounding
Mendelian Randomization Analysis
ASSOCIATION
3142 Public health care science, environmental and occupational health
educational attainment
Female
TRAITS
TRANSMISSION
Science
Biology
Population stratification
Polymorphism, Single Nucleotide
Article
General Biochemistry, Genetics and Molecular Biology
BMI
03 medical and health sciences
Medical research
SDG 3 - Good Health and Well-being
Mendelian randomization
Genetics
LINKAGE
Humans
Matematikk og Naturvitenskap: 400 [VDP]
COMMON
Linkage (software)
EDUCATIONAL-ATTAINMENT
Assortative mating
Gene-environment correlation
General Chemistry
confounding
BODY-MASS INDEX
3141 Health care science
030104 developmental biology
Matematikk og Naturvitenskap: 400::Basale biofag: 470::Genetikk og genomikk: 474 [VDP]
INFERENCE
lcsh:Q
DISEQUILIBRIUM
Body mass index
height
Demography
Subjects
Details
- Language :
- English
- ISSN :
- 20411723
- Volume :
- 11
- Issue :
- 1
- Database :
- OpenAIRE
- Journal :
- Nature Communications
- Accession number :
- edsair.doi.dedup.....71b4147acf9875c018191bb0292484fe