Exploring the association of genetic factors with participation in the Avon Longitudinal Study of Parents and Children
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Abstract
Background: It is often assumed that selection (including participation and dropout) does not represent an important source of bias in genetic studies. However, there is little evidence to date on the effect of genetic factors on participation. Methods: Using data on mothers (N = 7486) and children (N = 7508) from the Avon Longitudinal Study of Parents and Children, we: (i) examined the association of polygenic risk scores for a range of sociodemographic and lifestyle characteristics and health conditions related to continued participation; (ii) investigated whether associations of polygenic scores with body mass index (BMI; derived from self-reported weight and height) and self-reported smoking differed in the largest sample with genetic data and a subsample who participated in a recent follow-up; and (iii) determined the proportion of variation in participation explained by common genetic variants, using genome-wide data. Results: We found evidence that polygenic scores for higher education, agreeableness and openness were associated with higher participation; and polygenic scores for smoking initiation, higher BMI, neuroticism, schizophrenia, attention-deficit hyperactivity disorder (ADHD) and depression were associated with lower participation. Associations between the polygenic score for education and self-reported smoking differed between the largest sample with genetic data [odds ratio (OR) for ever smoking per standard deviation (SD) increase in polygenic score: 0.85, 95% confidence interval (CI): 0.81, 0.89} and subsample (OR: 0.96, 95% CI: 0.89, 1.03). In genome-wide analysis, single nucleotide polymorphism based heritability explained 18-32% of variability in participation. Conclusions: Genetic association studies, including Mendelian randomization, can be biased by selection, including loss to follow-up. Genetic risk for dropout should be considered in all analyses of studies with selective participation.
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Use of family data to conduct MR analyses can account for confounding owing to dynastic effects and assortative mating.
“One solution that can account for confounding owing to dynastic effects and assortative mating is the use of family data to conduct the MR analyses.167,168”
From Mendelian randomization (2022) · cites this paper as [167]
Within-family MR requires data from either pairs of siblings or mother-father-child trios and allows for estimation of causal effects using MR after family-level structure has been taken into account.
“Within-family MR requires data from either pairs of siblings or mother–father–child trios and allows for estimation of causal effects using MR after family-level structure has been taken into account.164,167”
From Mendelian randomization (2022) · cites this paper as [167]
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- Authors
- Taylor, A. E., Jones, H. J., Sallis, H., Euesden, J., Stergiakouli, E., Davies, N. M., Zammit, S., Lawlor, D. A., Munafò, M. R., Davey Smith, G., & Tilling, K.
- Affiliations
- University Hospitals Bristol NHS Foundation Trust (GB)
- University of Bristol (GB)
- MRC Integrative Epidemiology Unit at the University of Bristol, Bristol, United Kingdom
- Corresponding author
- Tilling, Kate
- ORCID
- Venue
- International Journal of Epidemiology
- Publisher
- Oxford University Press (OUP)
- Published
- 2018-05-23
- Volume
- 47
- Issue
- 4
- Pages
- 1207-1216
- ISSN
- 0300-5771 (ISSN-L)
- 1464-3685
- PMC
- PMC6124613
- OpenAlex
- W2800807051
- Cited by
- 192
- References
- 45
- Citations by year
- 2026: 6 · 2025: 17 · 2024: 15 · 2023: 33 · 2022: 40 · 2021: 31 · 2020: 23 · 2019: 20 · 2018: 6
- FWCI
- 12.24
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- International Journal of Epidemiology (publishedVersion, cc-by)
- bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- ORCA Online Research @Cardiff (Cardiff University) (acceptedVersion)
- Explore Bristol Research (submittedVersion, cc-by)
- Bristol Research (University of Bristol) (submittedVersion, cc-by)
- Funders
- Medical Research Council and Wellcome (102215/2/13/2)
- University of Bristol
- British Heart Foundation, Cancer Research UK, Economic and Social Research Council
- UK Medical Research Council (MC_UU_12013/1, MC_UU_12013/5, MC_UU_12013/6, MC_UU_12013/9, MR/M006727/1)
- National Institute for Health Research
- Clinical Research Collaboration
- NIHR
- Biomedical Research Centre at University Hospitals Bristol NHS Foundation Trust
- MRC
- NHS
- Department of Health
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
- Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Ethics in Clinical Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetics and Physical Performance
- Keywords
- research participation, loss to follow-up, selection bias, polygenic risk score, body mass index, smoking, educational attainment, personality traits, schizophrenia, attention deficit hyperactivity disorder, depression, Avon Longitudinal Study of Parents and Children
- MeSH terms
- Adolescent, Child, Child, Preschool, Female, United Kingdom, Humans, Infant, Infant, Newborn, Longitudinal Studies, Male, Risk Factors, Genetic Variation, Selection Bias, Body Mass Index, Genetic Predisposition to Disease, Multifactorial Inheritance, Polymorphism, Single Nucleotide, Genome-Wide Association Study, Young Adult
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