Genetic and environmental contributions to co-occurring physical health conditions in autism spectrum condition and attention-deficit/hyperactivity disorder

Pei-Yin Pan; Mark J Taylor; Henrik Larsson; Catarina Almqvist; Paul Lichtenstein; Sebastian Lundström; Sven Bölte

doi:10.1186/s13229-023-00548-3

Genetic and environmental contributions to co-occurring physical health conditions in autism spectrum condition and attention-deficit/hyperactivity disorder

Mol Autism. 2023 Apr 21;14(1):17. doi: 10.1186/s13229-023-00548-3.

Authors

Pei-Yin Pan¹, Mark J Taylor², Henrik Larsson², Catarina Almqvist^{2

3}, Paul Lichtenstein², Sebastian Lundström^{4

5}, Sven Bölte^{6

7

8}

Affiliations

¹ Center of Neurodevelopmental Disorders (KIND), Centre for Psychiatry Research; Department of Women's and Children's Health, Karolinska Institutet & Stockholm Health Care Services, Region Stockholm, Gävlegatan 22, 11330, Stockholm, Sweden. pei-yin.pan@ki.se.
² Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Berzelius Väg 8, Solna, 17165, Stockholm, Sweden.
³ Lung and Allergy Unit, Astrid Lindgren Children's Hospital, Karolinska University Hospital, Eugeniavägen 23, Solna, 17164, Stockholm, Sweden.
⁴ Gillberg Neuropsychiatry Centre, University of Gothenburg, Kungsgatan 12, 41119, GothenburgGöteborg, Sweden.
⁵ Centre for Ethics, Law, and Mental Health, University of Gothenburg, Universitetsplatsen 1, 41124, Gothenburg, Sweden.
⁶ Center of Neurodevelopmental Disorders (KIND), Centre for Psychiatry Research; Department of Women's and Children's Health, Karolinska Institutet & Stockholm Health Care Services, Region Stockholm, Gävlegatan 22, 11330, Stockholm, Sweden.
⁷ Child and Adolescent Psychiatry, Stockholm Health Care Services, Region Stockholm, Solnavägen 1E, 113 65, Stockholm, Sweden.
⁸ Curtin Autism Research Group, Curtin School of Allied Health, Curtin University, Kent Street, Bentley, Perth, WA, 6102, Australia.

Abstract

Background: Autism spectrum condition and attention-deficit/hyperactivity disorder (ADHD) are associated with a range of physical health conditions. The aim of this study was to examine the etiological components contributing to co-occurring physical health conditions in autism and ADHD.

Methods: In this nationwide Child and Adolescent Twin Study in Sweden, we analyzed data from 10,347 twin pairs aged 9 and 12. Clinical diagnoses of autism, ADHD, and physical health conditions were identified through the Swedish National Patient Register. Subclinical phenotypes of autism and ADHD were defined by symptom thresholds on a standardized parent-interview, the Autism-Tics, ADHD, and Other Comorbidities inventory. Associations between physical health conditions and autism/ADHD phenotypes were examined using generalized estimating equations. Bivariate twin models were applied to estimate the extent to which genetic and environmental risk factors accounted for physical health comorbidities.

Results: Similar patterns of association with physical health conditions were found in clinical and subclinical autism/ADHD, with odds ratios ranging from 1.31 for asthma in subclinical ADHD to 8.03 for epilepsy in clinical autism. The estimated genetic correlation (r_a) with epilepsy was 0.50 for clinical autism and 0.35 for subclinical autism. In addition, a modest genetic correlation was estimated between clinical autism and constipation (r_a = 0.31), functional diarrhea (r_a = 0.27) as well as mixed gastrointestinal disorders (r_a = 0.30). Genetic effects contributed 0.86 for mixed gastrointestinal disorders in clinical ADHD (r_a = 0.21). Finally, subclinical ADHD shared genetic risk factors with epilepsy, constipation, and mixed gastrointestinal disorders (r_a = 0.30, 0.17, and 0.17, respectively).

Limitations: Importantly, since medical records from primary care were not included in the registry data used, we probably identified only more severe rather than the full range of physical health conditions. Furthermore, it needs to be considered that the higher prevalence of physical health conditions among autistic children and children with ADHD could be associated with the increased number of medical visits.

Conclusions: Shared genetic effects contribute significantly to autism and ADHD phenotypes with the co-occurring physical health conditions across different organ systems, including epilepsy and gastrointestinal disorders. The shared genetic liability with co-occurring physical health conditions was present across different levels of autism and ADHD symptom severity.

Keywords: ADHD; Autism; Comorbidity; Etiology; Genetics; Twin study.

Publication types

Twin Study
Research Support, Non-U.S. Gov't

MeSH terms

Attention Deficit Disorder with Hyperactivity* / complications
Attention Deficit Disorder with Hyperactivity* / epidemiology
Attention Deficit Disorder with Hyperactivity* / genetics
Autism Spectrum Disorder* / complications
Autism Spectrum Disorder* / epidemiology
Autism Spectrum Disorder* / genetics
Autistic Disorder* / epidemiology
Comorbidity
Constipation / complications
Constipation / epidemiology
Epilepsy* / complications
Humans