3-generation family medical histories of mental, neurologic, cardiometabolic, birth defect, asthma, allergy, and autoimmune conditions associated with autism

• Type of Material: Article
• Authors: Diana Schendel, Drexel University; Linda Ejlskov, Aarhus University; Morten Overgaard, Aarhus University; Zeal Jinwala, Drexel University; Viktor Kim, Drexel University; Erik Parner, Aarhus University; Amy E. Kalkbrenner, University of Wisconsin, Milwaukee; Chirstine Ladd Acosta, Johns Hopkins University; Dani Fallin, Emory University; Sherlly Xie, Drexel University; Preben Bo Mortensen, Aarhus University; Brian k. Lee, Drexel University
• Language: English
• Date: 2024-06-14
• Publisher: NIH
• Publication Version: Preprint (Prior to Peer Review)
• Copyright Statement: The copyright holder for this preprint is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.
• License: Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International
• Final Published Version (URL): https://doi.org/10.1101/2023.11.03.23298042
• Title of Journal or Parent Work: medRxiv
• Start Page: 23298042
• Grant/Funding Information: The study was supported by the Lundbeck Foundation (iPSYCH, Grant numbers R102-A9118 and R155–2014-1724), the National Institute of Environmental Health Sciences of the National Institutes of Health under Award No. R01ES026993, and the National Institute of Neurologic Disorders and Stroke of the National Institutes of Health under Award No. R01 NS131433.
• Keywords: allergy; asthma; neurologic; birth defect; mental disorder; cardiometabolic; autism; autoimmune; family history
• Research Categories: Health Sciences, Epidemiology; Biology, Genetics

Abstract

The relatively few conditions and family members investigated in autism family health history limits etiologic understanding. For more comprehensive understanding and hypothesis-generation we produced an open-source catalogue of autism associations with family histories of mental, neurologic, cardiometabolic, birth defect, asthma, allergy, and autoimmune conditions. All live births in Denmark, 1980–2012, of Denmark-born parents (1,697,231 births), and their 3-generation family members were followed through April 10, 2017 for each of 90 diagnoses (including autism), emigration or death. Adjusted hazard ratios (aHR) were estimated via Cox regression for each diagnosis-family member type combination, adjusting for birth year, sex, birth weight, gestational age, parental ages at birth, and number of family member types of index person; aHRs also calculated for sex-specific co-occurrence of each disorder. We obtained 6,462 individual family history aHRS across autism overall (26,840 autistic persons; 1.6% of births), by sex, and considering intellectual disability (ID); and 350 individual co-occurrence aHRS. Results are catalogued in interactive heat maps and down-loadable data files: https://ncrr-au.shinyapps.io/asd-riskatlas/ and interactive graphic summaries: https://public.tableau.com/views/ASDPlots_16918786403110/e-Figure5. While primarily for reference material or use in other studies (e.g., meta-analyses), results revealed considerable breadth and variation in magnitude of familial health history associations with autism by type of condition, family member type, sex of the family member, side of the family, sex of the index person, and ID status, indicative of diverse genetic, familial, and non-genetic autism etiologic pathways. Careful attention to sources of autism likelihood in family health history, aided by our open data resource, may accelerate understanding of factors underlying neurodiversity.