TY - JOUR
T1 - Method for Testing Etiologic Heterogeneity Among Non-Competing Diagnoses, Applied to Impact of Perinatal Exposures on Autism and Attention Deficit Hyperactivity Disorder
AU - Kalkbrenner, Amy E.
AU - Zheng, Cheng
AU - Yu, Justin
AU - Jenson, Tara E.
AU - Kuhlwein, Thomas
AU - Ladd-Acosta, Christine
AU - Grove, Jakob
AU - Schendel, Diana
N1 - Publisher Copyright:
© 2024 The Author(s). Published by Wolters Kluwer Health, Inc.
PY - 2024/9/1
Y1 - 2024/9/1
N2 - 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 subcategorization because these disorders are heterogeneous and frequently co-occur. Existing methods to quantify etiologic heterogeneity are not appropriate for noncompeting 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 codiagnosis: 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. Conclusion: Our method allowed the calculation of appropriate P values to test the 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.
AB - 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 subcategorization because these disorders are heterogeneous and frequently co-occur. Existing methods to quantify etiologic heterogeneity are not appropriate for noncompeting 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 codiagnosis: 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. Conclusion: Our method allowed the calculation of appropriate P values to test the 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.
KW - attention deficit hyperactivity disorder
KW - autism
KW - co-diagnosis
KW - etiologic heterogeneity
KW - neurodevelopment
KW - smoking in pregnancy
KW - urban residence
UR - http://www.scopus.com/inward/record.url?scp=85199258405&partnerID=8YFLogxK
U2 - 10.1097/EDE.0000000000001760
DO - 10.1097/EDE.0000000000001760
M3 - Journal article
C2 - 39024025
AN - SCOPUS:85199258405
SN - 1044-3983
VL - 35
SP - 689
EP - 700
JO - Epidemiology
JF - Epidemiology
IS - 5
M1 - 1760
ER -