Complications during pregnancy and birth and offspring risk for schizophrenia and other psychoses: Untangling Causality and Genetic Influences.

Schizophrenia and related psychoses are associated with obstetric complications but whether these associations are causal is yet to be explored.

This study investigates the relationship between specific complications (e.g. preterm birth, growth restriction, hypoxia), genetic predisposition, and schizophrenia risk using a comprehensive approach integrating large-scale register-based cohort studies, genetically-informed designs, individual genotypes, and detailed familial health data.This is finally possible since we are updating our register linkage, Psychiatry Sweden, to include follow-up data until 2022, thereby enhancing our power (N=25 000 individuals with schizophrenia spectrum disorders).

This presents an opportunity to combine a total-population cohort study with genetically-informed designs, such as sibling- and cousin-comparison studies, and pedigree-based family psychiatric history risk scores using familial health records in up to third degree relatives, to enhance the robustness of our causal inference.

Finally, we have now genotyped a sub-set of 3000 individuals with schizophrenia and 2500 controls.

Integrating  individual genotype data with health registers, we will examine the joint influence of genetics and obstetric complications on schizophrenia risk using polygenic risk scores and tentatively pathway analyses.Together these studies will add to the etiological knowledge about schizophrenia but also whether maternity care could constitute a way of prevention.