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.

ASD and schizophrenia show distinct developmental profiles in common genetic overlap with population-based social communication difficulties

“…Using for simplicity a PGS threshold of P T <0.05, there was little evidence for a relationship between sample-dropout and ASD-PGS, especially after adjustment for maternal educational level (age 8: OR(SE)=0.99(0.03), P =0.82), although there was support for an association with schizophrenia-PGS (age 17: OR(SE)=1.10(0.03), P =0.000050), consistent with previous studies52.…”

“…For instance, it is possible that the genetic overlap between schizophrenia and social-communication difficulties has been underestimated, as SCDC-missingness, and more generally study non-participation52, has been related to common genetic risk for schizophrenia. In contrast, there was little evidence for a link between SCDC-missingness and common ASD risk.…”

Genetic predictors of participation in optional components of UK Biobank

“…These include: lower intelligence and educational attainment; higher adiposity, and increased liability to ADHD, neuroticism and schizophrenia. Many of these were previously identified in the ALSPAC study 1,5 , previous UK Biobank study analyses 18 and Generation Scotland 18 . This implies that missingness of all the variables collected in the optional components of UK Biobank will be influenced by these underlying traits.…”

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

“…Here, we extend previous work relating participation and polygenic risk for schizophrenia and autism in ALSPAC 13 , 14 by: (i) investigating polygenic scores for other factors which could influence participation in the ALSPAC mothers and children; (ii) investigating the potential impact of selection bias by comparing associations between genetic factors and measured phenotypes in the largest sample with genetic data and a more selected subsample; and (iii) conducting genome-wide association studies of participation measures.…”