TY - JOUR
T1 - 3-generation family histories of mental, neurologic, cardiometabolic, birth defect, asthma, allergy, and autoimmune conditions associated with autism
T2 - An open-source catalog of findings
AU - Schendel, Diana
AU - Ejlskov, Linda
AU - Overgaard, Morten
AU - Jinwala, Zeal
AU - Kim, Viktor
AU - Parner, Erik
AU - Kalkbrenner, Amy E
AU - Ladd Acosta, Christine
AU - Fallin, M Danielle
AU - Xie, Sherlly
AU - Mortensen, Preben Bo
AU - Lee, Brian K
N1 - © 2024 The Author(s). Autism Research published by International Society for Autism Research and Wiley Periodicals LLC.
PY - 2024/10
Y1 - 2024/10
N2 - The relatively few conditions and family member types (e.g., sibling, parent) considered in investigations of family health history in autism spectrum disorder (ASD, or autism) limits understanding of the role of family history in autism etiology. For more comprehensive understanding and hypothesis-generation, we produced an open-source catalog 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 6462 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 cataloged in interactive heat maps and down-loadable data files: https://ncrr-au.shinyapps.io/asd-riskatlas/ and interactive graphic summaries: https://public.tableau.com/app/profile/diana.schendel/viz/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 nongenetic 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.
AB - The relatively few conditions and family member types (e.g., sibling, parent) considered in investigations of family health history in autism spectrum disorder (ASD, or autism) limits understanding of the role of family history in autism etiology. For more comprehensive understanding and hypothesis-generation, we produced an open-source catalog 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 6462 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 cataloged in interactive heat maps and down-loadable data files: https://ncrr-au.shinyapps.io/asd-riskatlas/ and interactive graphic summaries: https://public.tableau.com/app/profile/diana.schendel/viz/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 nongenetic 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.
KW - allergy
KW - asthma
KW - autism
KW - autoimmune
KW - birth defect
KW - cardiometabolic
KW - family history
KW - mental disorder
KW - neurologic
UR - http://www.scopus.com/inward/record.url?scp=85204209232&partnerID=8YFLogxK
U2 - 10.1002/aur.3232
DO - 10.1002/aur.3232
M3 - Journal article
C2 - 39283002
SN - 1939-3792
VL - 17
SP - 2144
EP - 2155
JO - Autism Research
JF - Autism Research
IS - 10
ER -