RT Journal Article
SR Electronic
T1 The molecular genetics of participation in the Avon Longitudinal Study of Parents and Children
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 206698
DO 10.1101/206698
A1 Amy E. Taylor
A1 Hannah J. Jones
A1 Hannah Sallis
A1 Jack Euesden
A1 Evie Stergiakouli
A1 Neil M. Davies
A1 Stanley Zammit
A1 Debbie A. Lawlor
A1 Marcus R. Munafò
A1 George Davey Smith
A1 Kate Tilling
YR 2017
UL http://biorxiv.org/content/early/2017/10/20/206698.abstract
AB 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:0.95, 95% CI:0.88,1.02). In genome-wide analysis, single nucleotide polymorphism based heritability explained 17-31% 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.