Diana Paksarian1, Betina B Trabjerg2, Kathleen R Merikangas1, Ole Mors3, Anders D Børglum4, David M Hougaard5, Merete Nordentoft6, Thomas Werge7, Carsten B Pedersen8, Preben B Mortensen2, Esben Agerbo2, Henriette Thisted Horsdal9. 1. National Institute of Mental Health, Maryland, USA. 2. National Center for Register-Based Research, Business and Social Sciences, Aarhus University; The Lundbeck Foundation Initiative for Integrative Psychiatric Research; and Centre for Integrated Register-Based Research, Aarhus University, Denmark. 3. The Lundbeck Foundation Initiative for Integrative Psychiatric Research; and Psychosis Research Unit, Aarhus University Hospital - Psychiatry, Denmark. 4. The Lundbeck Foundation Initiative for Integrative Psychiatric Research; Department of Biomedicine and Centre for Integrative Sequencing, iSEQ, Aarhus University; and Center for Genomics and Personalized Medicine, Denmark. 5. Danish Center for Neonatal Screening, Statens Serum Institut, Denmark. 6. Copenhagen Research Centre for Mental Health, Mental Health Centre Copenhagen, Capital Region of Denmark, Copenhagen University Hospital; and The Lundbeck Foundation Initiative for Integrative Psychiatric Research, Denmark. 7. Institute of Biological Psychiatry, Mental Health Services Copenhagen; Department of Clinical Medicine, University of Copenhagen; and The Lundbeck Foundation Initiative for Integrative Psychiatric Research, Denmark. 8. National Center for Register-Based Research, Business and Social Sciences, Aarhus University; The Lundbeck Foundation Initiative for Integrative Psychiatric Research; Centre for Integrated Register-Based Research, Aarhus University, Denmark. 9. National Center for Register-Based Research, Business and Social Sciences, Aarhus University; and The Lundbeck Foundation Initiative for Integrative Psychiatric Research, Denmark.
Abstract
BACKGROUND: Residential mobility during upbringing, and especially adolescence, is associated with multiple negative mental health outcomes. However, whether associations are confounded by unmeasured familial factors, including genetic liability, is unclear. AIMS: We used a population-based case-cohort study to assess whether polygenic risk scores (PRSs) for schizophrenia, bipolar disorder and major depression were associated with mobility from ages 10-14 years, and whether PRS and parental history of mental disorder together explained associations between mobility and each disorder. METHOD: Information on cases (n = 4207 schizophrenia, n = 1402 bipolar disorder, n = 18 215 major depression) and a random population sample (n = 17 582), born 1981-1997, was linked between Danish civil and psychiatric registries. Genome-wide data were obtained from the Danish Neonatal Screening Biobank and PRSs were calculated based on results of separate, large meta-analyses. RESULTS: PRSs for schizophrenia and major depression were weakly associated with moving once (odds ratio 1.07, 95% CI 1.00-1.16; and odds ratio 1.10, 95% CI 1.04-1.17, respectively), but not twice or three or more times. Mobility was positively associated with each disorder, with more moves associated with greater risk. Adjustment for PRS produced slight reductions in the magnitude of associations. Adjustment for PRS and parental history of mental disorder together reduced estimates by 5-11%. In fully adjusted models mobility was associated with all three disorders; hazard ratios ranged from 1.33 (95% CI 1.08-1.62; one move and bipolar disorder) to 3.05 (95% CI 1.92-4.86; three or more moves and bipolar disorder). CONCLUSIONS: Associations of mobility with schizophrenia, bipolar disorder and depression do not appear to be attributable to genetic liability as measured here. Potential familial confounding of mobility associations may be predominantly environmental in nature.
BACKGROUND: Residential mobility during upbringing, and especially adolescence, is associated with multiple negative mental health outcomes. However, whether associations are confounded by unmeasured familial factors, including genetic liability, is unclear. AIMS: We used a population-based case-cohort study to assess whether polygenic risk scores (PRSs) for schizophrenia, bipolar disorder and major depression were associated with mobility from ages 10-14 years, and whether PRS and parental history of mental disorder together explained associations between mobility and each disorder. METHOD: Information on cases (n = 4207 schizophrenia, n = 1402 bipolar disorder, n = 18 215 major depression) and a random population sample (n = 17 582), born 1981-1997, was linked between Danish civil and psychiatric registries. Genome-wide data were obtained from the Danish Neonatal Screening Biobank and PRSs were calculated based on results of separate, large meta-analyses. RESULTS: PRSs for schizophrenia and major depression were weakly associated with moving once (odds ratio 1.07, 95% CI 1.00-1.16; and odds ratio 1.10, 95% CI 1.04-1.17, respectively), but not twice or three or more times. Mobility was positively associated with each disorder, with more moves associated with greater risk. Adjustment for PRS produced slight reductions in the magnitude of associations. Adjustment for PRS and parental history of mental disorder together reduced estimates by 5-11%. In fully adjusted models mobility was associated with all three disorders; hazard ratios ranged from 1.33 (95% CI 1.08-1.62; one move and bipolar disorder) to 3.05 (95% CI 1.92-4.86; three or more moves and bipolar disorder). CONCLUSIONS: Associations of mobility with schizophrenia, bipolar disorder and depression do not appear to be attributable to genetic liability as measured here. Potential familial confounding of mobility associations may be predominantly environmental in nature.
Entities:
Keywords:
Epidemiology; family history; genetic confounding; geographic mobility; risk factor
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