Clinical and genetic contributions to medical comorbidity in bipolar disorder: a study using electronic health records-linked biobank data.

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  • Additional Information
    • Source:
      Publisher: Nature Publishing Group Specialist Journals Country of Publication: England NLM ID: 9607835 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1476-5578 (Electronic) Linking ISSN: 13594184 NLM ISO Abbreviation: Mol Psychiatry Subsets: MEDLINE
    • Publication Information:
      Publication: 2000- : Houndmills, Basingstoke, UK : Nature Publishing Group Specialist Journals
      Original Publication: Houndmills, Hampshire, UK ; New York, NY : Stockton Press, c1996-
    • Subject Terms:
      Bipolar Disorder*/genetics ; Bipolar Disorder*/epidemiology ; Electronic Health Records* ; Comorbidity* ; Biological Specimen Banks* ; Multifactorial Inheritance*/genetics ; Phenotype*; Humans ; Female ; Male ; Middle Aged ; Aged ; Genome-Wide Association Study/methods ; Genetic Predisposition to Disease/genetics ; Adult ; Aged, 80 and over ; Risk Factors ; Phenomics/methods
    • Abstract:
      Bipolar disorder is a chronic and complex polygenic disease with high rates of comorbidity. However, the independent contribution of either diagnosis or genetic risk of bipolar disorder to the medical comorbidity profile of individuals with the disease remains unresolved. Here, we conducted a multi-step phenome-wide association study (PheWAS) of bipolar disorder using phenomes derived from the electronic health records of participants enrolled in the Mayo Clinic Biobank and the Mayo Clinic Bipolar Disorder Biobank. First, we explored the conditions associated with a diagnosis of bipolar disorder by conducting a phenotype-based PheWAS followed by LASSO-penalized regression to account for correlations within the phenome. Then, we explored the conditions associated with bipolar disorder polygenic risk score (BD-PRS) using a PRS-based PheWAS with a sequential exclusion approach to account for the possibility that diagnosis, instead of genetic risk, may drive such associations. 53,386 participants (58.7% women) with a mean age at analysis of 67.8 years (SD = 15.6) were included. A bipolar disorder diagnosis (n = 1479) was associated with higher rates of psychiatric conditions, injuries and poisonings, endocrine/metabolic and neurological conditions, viral hepatitis C, and asthma. BD-PRS was associated with psychiatric comorbidities but, in contrast, had no positive associations with general medical conditions. While our findings warrant confirmation with longitudinal-prospective studies, the limited associations between bipolar disorder genetics and medical conditions suggest that shared environmental effects or environmental consequences of diagnosis may have a greater impact on the general medical comorbidity profile of individuals with bipolar disorder than its genetic risk.
      (© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)
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    • Grant Information:
      R01 MH121924 United States MH NIMH NIH HHS; R01MH121924 U.S. Department of Health & Human Services | NIH | National Institute of Mental Health (NIMH)
    • Publication Date:
      Date Created: 20240329 Date Completed: 20240924 Latest Revision: 20241109
    • Publication Date:
      20241109
    • Accession Number:
      PMC11544602
    • Accession Number:
      10.1038/s41380-024-02530-8
    • Accession Number:
      38548982