Exploring the association of genetic factors with participation in the Avon Longitudinal Study of Parents and Children

• Published in: International journal of epidemiology 2018-08, Vol.47 (4), p.1207-1216
• Main Authors: Taylor, Amy E, Jones, Hannah J, Sallis, Hannah, Euesden, Jack, Stergiakouli, Evie, Davies, Neil M, Zammit, Stanley, Lawlor, Debbie A, Munafò, Marcus R, Davey Smith, George, Tilling, Kate
• Format: Article
• Language: English
• Subjects: Adolescent; Body Mass Index; Child; Child, Preschool; Female; Genetic Epidemiology; Genetic Predisposition to Disease; Genetic Variation; Genome-Wide Association Study; Humans; Infant; Infant, Newborn; Longitudinal Studies; Male; Multifactorial Inheritance; Polymorphism, Single Nucleotide; Risk Factors; Selection Bias; United Kingdom; Young Adult
• ISSN: 0300-5771; 1464-3685
• DOI: 10.1093/ije/dyy060

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.