Examining selection bias in a population-based cohort study of 522 children with familial high risk of schizophrenia or bipolar disorder, and controls: The Danish High Risk and Resilience Study VIA 7

Soc Psychiatry Psychiatr Epidemiol. 2023 Jan;58(1):113-140. doi: 10.1007/s00127-022-02338-3. Epub 2022 Sep 10.


Purpose: Knowledge about representativity of familial high-risk studies of schizophrenia and bipolar disorder is essential to generalize study conclusions. The Danish High Risk and Resilience Study (VIA 7), a population-based case-control familial high-risk study, creates a unique opportunity for combining assessment and register data to examine cohort representativity.

Methods: Through national registers, we identified the population of 11,959 children of parents with schizophrenia (FHR-SZ) or bipolar disorder (FHR-BP) and controls from which the 522 children participating in The VIA 7 Study (202 FHR-SZ, 120 FHR-BP and 200 controls) were selected. Socio-economic and health data were obtained to compare high-risk groups and controls, and participants versus non-participants. Selection bias impact on results was analyzed through inverse probability weights.

Results: In the total sample of 11,959 children, FHR-SZ and FHR-BP children had more socio-economic and health disadvantages than controls (p < 0.001 for most). VIA 7 non-participants had a poorer function, e.g. more paternal somatic and mental illness (p = 0.02 and p = 0.04 for FHR-SZ), notifications of concern (FHR-BP and PBC p < 0.001), placements out of home (p = 0.03 for FHR-SZ), and lower level of education (p ≤ 0.01 for maternal FHR-SZ and FHR-BP, p = 0.001 for paternal FHR-BP). Inverse probability weighted analyses of results generated from the VIA Study showed minor changes in study findings after adjustment for the found selection bias.

Conclusions: Familial high-risk families have multiple socio-economic and health disadvantages. In The VIA 7 Study, although comparable regarding mental illness severity after their child's birth, socioeconomic and health disadvantages are more profound amongst non-participants than amongst participants.

Keywords: Familial high-risk; Generalizability; Representativity; Severe parental mental illness; Socio-economy.

MeSH terms

  • Bipolar Disorder* / epidemiology
  • Bipolar Disorder* / genetics
  • Child
  • Cohort Studies
  • Denmark / epidemiology
  • Humans
  • Male
  • Schizophrenia* / epidemiology
  • Selection Bias