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

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=7,486) and children (N=7,508) from the Avon Longitudinal Study of Parents and Children, we 1) examined the association of polygenic risk scores for a range of socio-demographic, lifestyle characteristics and health conditions related to continued participation, 2) 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 sub-sample who participated in a recent follow-up and 3) 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, 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 (OR for ever smoking per SD increase in polygenic score:0.85, 95% CI:0.81,0.89) and sub-sample (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.