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Abstract
Spousal comparisons have been proposed as a design that can both reduce
confounding and estimate effects of the shared adulthood environment. However, assortative mating, the process by which individuals select phenotypically (dis)similar mates, could distort associations when comparing spouses. We evaluated the use of spousal comparisons, as in the within-spouse pair (WSP) model, for aetiological research such as genetic association studies.
We demonstrated that the WSP model can reduce confounding but may be
susceptible to collider bias arising from conditioning on assorted spouse pairs.
Analyses using UK Biobank spouse pairs found that WSP genetic association
estimates were smaller than estimates from random pairs for height, educational
attainment, and BMI variants. Within-sibling pair estimates, robust to demographic and parental effects, were also smaller than random pair estimates for height and educational attainment, but not for BMI.
WSP models, like other within-family models, may reduce confounding from
demographic factors in genetic association estimates, and so could be useful for
triangulating evidence across study designs to assess the robustness of findings.
However, WSP estimates should be interpreted with caution due to potential collider bias.
confounding and estimate effects of the shared adulthood environment. However, assortative mating, the process by which individuals select phenotypically (dis)similar mates, could distort associations when comparing spouses. We evaluated the use of spousal comparisons, as in the within-spouse pair (WSP) model, for aetiological research such as genetic association studies.
We demonstrated that the WSP model can reduce confounding but may be
susceptible to collider bias arising from conditioning on assorted spouse pairs.
Analyses using UK Biobank spouse pairs found that WSP genetic association
estimates were smaller than estimates from random pairs for height, educational
attainment, and BMI variants. Within-sibling pair estimates, robust to demographic and parental effects, were also smaller than random pair estimates for height and educational attainment, but not for BMI.
WSP models, like other within-family models, may reduce confounding from
demographic factors in genetic association estimates, and so could be useful for
triangulating evidence across study designs to assess the robustness of findings.
However, WSP estimates should be interpreted with caution due to potential collider bias.
| Original language | English |
|---|---|
| Article number | e1009883 |
| Number of pages | 18 |
| Journal | PLoS Genetics |
| Volume | 17 |
| Issue number | 11 |
| DOIs | |
| Publication status | Published - 4 Nov 2021 |
Bibliographical note
Funding Information:LJH, TB, TTM, GH, NMD and GDS are members of MRC Integrative Epidemiology Unit which is supported by the Medical Research Council (MRC) [MC_UU_00011/1] and the University of Bristol (principal investigator: GDS). NMD is supported by The Economics and Social Research Council (ESRC) via a Future Research Leaders grant [ES/N000757/1], a Norwegian Research Council Grant number 295989 and by the Health Foundation?s Efficiency Research Programme (Award 807293). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
Publisher Copyright:
© 2021 Howe et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Fingerprint
Dive into the research topics of 'Assortative mating and within-spouse pair comparisons'. Together they form a unique fingerprint.Projects
- 1 Finished
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IEU: MRC Integrative Epidemiology Unit Quinquennial renewal
Gaunt, L. F. (Principal Investigator) & Davey Smith, G. (Principal Investigator)
1/04/18 → 31/03/23
Project: Research