Exploring Parental and Genetic Liability Factors in Relation to Minor Physical Anomalies in the Danish High Risk and Resilience Study -VIA 7

Abstract

Background: Minor physical anomalies (MPAs) are markers of neurodevelopmental deviance that are associated with increased risk for subsequent development of schizophrenia, but their relationships to parental and genetic liability factors are largely unknown.

Objective: To examine if MPAs are associated with polygenic risk scores (PRS) for schizophrenia (PRS SZ ) or bipolar disorder (PRS BP ) or with parental history of these disorders.MethodThe sample comprised 381 seven-year-old children of whom 139 had familial high risk for schizophrenia (FHR-SZ), 92 high risk for bipolar disorder (FHR-BP) and 139 were population-based controls (PBC) matched with the FHR-SZ group for age, sex, and municipality. MPA assessment was guided as described by Waldrop and Halvorsen in 1971. DNA was obtained from saliva. Pregnancy-related data on maternal age, smoking, alcohol intake and medication were obtained from the biological mother.

Results: FHR-SZ status was associated with higher risk of MPAs of the mouth (OR=2.10, 95% CI 1.09-4.04) when compared to PBC and after adjustment for confounders. Overall, parental, or genetic liability for schizophrenia or bipolar disorder was not associated with a higher number of MPAs among offspring with the exception that a high PRS_SZ or a high PRS_BP was found to predict a curved fifth finger.

Conclusion: We found limited support that MPAs are mediated by genetic or familial liability to schizophrenia or bipolar disorder.

Note:
Funding Information: The Danish National Biobank resource is supported by the Novo Nordisk Foundation.

Declaration of Interests: The authors declare no financial interests or potential conflicts of interest.

Ethics Approval Statement: The study was approved by the Danish Data Protection Agency. Written informed consent was obtained from all adult participants and from the legal guardians of participating children. The genetic part of the study obtained ethical approval from the outset of the study.

Keywords: minor physical anomalies, Cohort studies, high-risk design, polygenic risk score, Schizophrenia