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Journal article
Method for Testing Etiologic Heterogeneity Among Non-Competing Diagnoses, Applied to Impact of Perinatal Exposures on Autism and Attention Deficit Hyperactivity Disorder
Epidemiology (Cambridge, Mass.), v 35(5), pp 689-700
Sep 2024
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
Background: Testing etiologic heterogeneity – whether a disorder subtype is more or less impacted by a risk factor, is important for understanding causal pathways and optimizing statistical power. The study of mental health disorders especially benefits from strategic sub-categorization because these disorders are heterogenous and frequently co-occur. Existing methods to quantify etiologic heterogeneity are not appropriate for non-competing events in an open cohort of variable-length follow-up. Thus, we developed a new method. Methods: We estimated risks from urban residence, maternal smoking during pregnancy, and parental psychiatric history, with subtypes defined by the presence or absence of a co-diagnosis: autism alone, attention deficit hyperactivity disorder (ADHD) alone, and joint diagnoses of autism+ADHD. To calculate the risk of a single diagnosis (e.g. autism alone), we subtracted the risk for autism+ADHD from the risk for autism overall. We tested the equivalency of average risk ratios over time, using a Wald-type test and bootstrapped standard errors. Results: Urban residence was most strongly linked with autism+ADHD and least with ADHD only; maternal smoking was associated with ADHD only but not autism only; and parental psychiatric history exhibited similar associations with all subgroups. Conclusions: Our method allowed the calculation of appropriate p values to test strength of association, informing etiologic heterogeneity wherein two of these three risk factors exhibited different impacts across diagnostic subtypes. The method used all available data, avoided neurodevelopmental outcome misclassification, exhibited robust statistical precision, and is applicable to similar heterogeneous complex conditions using common diagnostic data with variable follow-up.
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Details
- Title
- Method for Testing Etiologic Heterogeneity Among Non-Competing Diagnoses, Applied to Impact of Perinatal Exposures on Autism and Attention Deficit Hyperactivity Disorder
- Creators
- Amy E. Kalkbrenner (Corresponding Author) - University of Wisconsin–MilwaukeeCheng Zheng - University of Nebraska Medical CenterJustin Yu - Drexel University, A.J. Drexel Autism InstituteTara E. Jenson - University of Wisconsin–MilwaukeeThomas Kuhlwein - Lundbeck FoundationChristine Ladd-Acosta - Johns Hopkins UniversityJakob Grove - Lundbeck FoundationDiana Schendel - Drexel University, A.J. Drexel Autism Institute
- Publication Details
- Epidemiology (Cambridge, Mass.), v 35(5), pp 689-700
- Publisher
- Lippincott Williams & Wilkins
- Number of pages
- 12
- Grant note
- National Institute of Environmental Health Sciences of the National Institutes of Health: R01ES026993
Supported by the National Institute of Environmental Health Sciences of the National Institutes of Health under Award Number R01ES026993. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. Additional support came from an unrestricted grant from the Lundbeck Foundation (iPSYCH).
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- A.J. Drexel Autism Institute
- Web of Science ID
- WOS:001285400300007
- Scopus ID
- 2-s2.0-85199258405
- Other Identifier
- 991021894315504721
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- Collaboration types
- Domestic collaboration
- International collaboration
- Web of Science research areas
- Public, Environmental & Occupational Health