title: Association of Genetic Risk for Schizophrenia With Nonparticipation Over Time in a Population-Based Cohort Study.
abstract: Progress has recently been made in understanding the genetic basis of schizophrenia and other psychiatric disorders. Longitudinal studies are complicated by participant dropout, which could be related to the presence of psychiatric problems and associated genetic risk. We tested whether common genetic variants implicated in schizophrenia were associated with study nonparticipation among 7,867 children and 7,850 mothers from the Avon Longitudinal Study of Parents and Children (ALSPAC; 1991-2007), a longitudinal population cohort study. Higher polygenic risk scores for schizophrenia were consistently associated with noncompletion of questionnaires by study mothers and children and nonattendance at data collection throughout childhood and adolescence (ages 1-15 years). These associations persisted after adjustment for other potential correlates of nonparticipation. Results suggest that persons at higher genetic risk for schizophrenia are likely to be underrepresented in cohort studies, which will underestimate risk of this and related psychiatric, cognitive, and behavioral phenotypes in the population. Statistical power to detect associations with these phenotypes will be reduced, while analyses of schizophrenia-related phenotypes as outcomes may be biased by the nonrandom missingness of these phenotypes, even if multiple imputation is used. Similarly, in complete-case analyses, collider bias may affect associations between genetic risk and other factors associated with missingness.
authors.forename: Joanna
authors.initials: J
authors.lastname: Martin
authors.forename: Kate
authors.initials: K
authors.lastname: Tilling
authors.forename: Leon
authors.initials: L
authors.lastname: Hubbard
authors.forename: Evie
authors.initials: E
authors.lastname: Stergiakouli
authors.forename: Anita
authors.initials: A
authors.lastname: Thapar
authors.forename: George
authors.initials: G
authors.lastname: Davey Smith
authors.forename: Michael C
authors.initials: MC
authors.lastname: O'Donovan
authors.forename: Stanley
authors.initials: S
authors.lastname: Zammit
mesh_terms: D000293:Adolescent; D000342:Affective Symptoms / Q000453:epidemiology; D002648:Child; D002653:Child Behavior Disorders / Q000453:epidemiology; D002675:Child, Preschool; D003625:Data Collection / Q000592:standards / Q000706:statistics & numerical data; D005260:Female; D020022:Genetic Predisposition to Disease / Q000453:epidemiology*; D006801:Humans; D007223:Infant; D008137:Longitudinal Studies; D008297:Male; D009035:Mothers / Q000706:statistics & numerical data*; D015203:Reproducibility of Results; D012307:Risk Factors; D012559:Schizophrenia / Q000453:epidemiology* / Q000235:genetics*; D012737:Sex Factors; D012959:Socioeconomic Factors; D011795:Surveys and Questionnaires; D006113:United Kingdom
keywords: Avon Longitudinal Study of Parents and Children; attrition bias; cohort studies; genetic risk; longitudinal studies; schizophrenia; study nonparticipation