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

35 Pages Posted: 1 Mar 2022

See all articles by Holger Jelling Sørensen

Holger Jelling Sørensen

Mental Health Centre Copenhagen - CORE – Copenhagen Research Centre for Mental Health

Ditte Ellersgaard

affiliation not provided to SSRN

Jessica Ohland

affiliation not provided to SSRN

Carsten Hjorthøj

University of Copenhagen, Faculty of Health and Medical Sciences, Department of Public Health

Yunpeng Wang

affiliation not provided to SSRN

Jens R. Jepsen

affiliation not provided to SSRN

Camilla Christiani

affiliation not provided to SSRN

Nicoline Hemager

Mental Health Centre Copenhagen - CORE – Copenhagen Research Centre for Mental Health

Maja Gregersen

Mental Health Centre Copenhagen - CORE – Copenhagen Research Centre for Mental Health

Aja Greve

Lundbeck Foundation Initiative for Integrative Psychiatric Research (iPSYCH)

Anne Søndergaard

affiliation not provided to SSRN

Kathrine Spang

affiliation not provided to SSRN

Birgitte Burton

affiliation not provided to SSRN

Jamal Uddin

affiliation not provided to SSRN

Ron Nudel

affiliation not provided to SSRN

Jonas Bygbjerg-Grauholm

Lundbeck Foundation Initiative for Integrative Psychiatric Research (iPSYCH)

Thomas Werge

University of Copenhagen - Institute for Biological Psychiatry

Ole Mors

affiliation not provided to SSRN

Kerstin J. Plessen

Copenhagen University - Child and Adolescent Mental Health Centre

Anne Thorup

affiliation not provided to SSRN

Merete Nordentoft

Mental Health Centre Copenhagen - CORE – Copenhagen Research Centre for Mental Health

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 PRSSZ or a high PRSBP 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

Suggested Citation

Sørensen, Holger Jelling and Ellersgaard, Ditte and Ohland, Jessica and Hjorthøj, Carsten and Wang, Yunpeng and Jepsen, Jens R. and Christiani, Camilla and Hemager, Nicoline and Gregersen, Maja and Greve, Aja and Søndergaard, Anne and Spang, Kathrine and Burton, Birgitte and Uddin, Jamal and Nudel, Ron and Bygbjerg-Grauholm, Jonas and Werge, Thomas and Mors, Ole and Plessen, Kerstin J. and Thorup, Anne and Nordentoft, Merete, Exploring Parental and Genetic Liability Factors in Relation to Minor Physical Anomalies in the Danish High Risk and Resilience Study -VIA 7. Available at SSRN: https://ssrn.com/abstract=4046693

Holger Jelling Sørensen (Contact Author)

Mental Health Centre Copenhagen - CORE – Copenhagen Research Centre for Mental Health ( email )

Copenhagen
Denmark

Ditte Ellersgaard

affiliation not provided to SSRN ( email )

No Address Available

Jessica Ohland

affiliation not provided to SSRN ( email )

No Address Available

Carsten Hjorthøj

University of Copenhagen, Faculty of Health and Medical Sciences, Department of Public Health ( email )

Yunpeng Wang

affiliation not provided to SSRN ( email )

No Address Available

Jens R. Jepsen

affiliation not provided to SSRN ( email )

No Address Available

Camilla Christiani

affiliation not provided to SSRN ( email )

No Address Available

Nicoline Hemager

Mental Health Centre Copenhagen - CORE – Copenhagen Research Centre for Mental Health ( email )

Copenhagen
Denmark

Maja Gregersen

Mental Health Centre Copenhagen - CORE – Copenhagen Research Centre for Mental Health ( email )

Copenhagen
Denmark

Aja Greve

Lundbeck Foundation Initiative for Integrative Psychiatric Research (iPSYCH) ( email )

Aarhus
Denmark

Anne Søndergaard

affiliation not provided to SSRN ( email )

No Address Available

Kathrine Spang

affiliation not provided to SSRN ( email )

No Address Available

Birgitte Burton

affiliation not provided to SSRN ( email )

No Address Available

Jamal Uddin

affiliation not provided to SSRN ( email )

No Address Available

Ron Nudel

affiliation not provided to SSRN ( email )

No Address Available

Jonas Bygbjerg-Grauholm

Lundbeck Foundation Initiative for Integrative Psychiatric Research (iPSYCH) ( email )

Thomas Werge

University of Copenhagen - Institute for Biological Psychiatry ( email )

Ole Mors

affiliation not provided to SSRN ( email )

No Address Available

Kerstin J. Plessen

Copenhagen University - Child and Adolescent Mental Health Centre ( email )

Anne Thorup

affiliation not provided to SSRN ( email )

No Address Available

Merete Nordentoft

Mental Health Centre Copenhagen - CORE – Copenhagen Research Centre for Mental Health ( email )

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