Mental Illness in Partially-Genotyped Siblings: An Application of the Phenotype Differences Model in Finnish Register Data
The model builds upon the sibling fixed-effects approach to study within-family genetic variation. Fixed-effects sibling analysis controls for shared family-level factors such as parental genes, parental psychopathology, and socioeconomic status. It also accounts for how parental genes shape the family environment, assortative mating, and population stratification. However, sibling-specific genetic variation remains.
Main hypotheses: 1) There are social disparities in the genetic predisposition for developing a mental illness, and 2) A higher genetic risk for mental illness is more likely to be realized among children with poorer parental resources.
We utilize comprehensive data from social and health registers of the Finnish population linked to genetic information of 21,599 sibling pairs (50.2% female). The main predictors are polygenic scores and parental education (37.8% highly educated). Study outcomes are the onset of a mental illness based on psychiatric diagnoses recorded in public specialized health care and psychotropic medication costs.
Individuals from lower social strata were found to carry more alleles associated with mental illness. The study findings suggest that genetic effects are generally smaller within families and likely moderated by the family environment, such as the level of parental education. However, estimating gene-environment interactions proves to be notoriously difficult, with many results not robust enough to hold up under stringent statistical tests.
Applying the PDiffM merged with full population register data allows for conducting dyadic genetic and gene by environment interaction analyses. Overall, the research highlights the importance of within-family approaches in dissecting the genetic and environmental contributions to mental illness.