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

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 (ra) 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 (ra = 0.31), functional diarrhea (ra = 0.27) as well as mixed gastrointestinal disorders (ra = 0.30). Genetic effects contributed 0.86 for mixed gastrointestinal disorders in clinical ADHD (ra = 0.21). Finally, subclinical ADHD shared genetic risk factors with epilepsy, constipation, and mixed gastrointestinal disorders (ra = 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. Supplementary Information The online version contains supplementary material available at 10.1186/s13229-023-00548-3.

A. Motor control The essential aspect of each question is whether the problem/peculiarity has been pronounced compared to peers during any period of life Yes Yes, to some extent No 1 Does he/she have problems coordinating movements smoothly?
If "Yes" or "Yes, to some extent" to this question: A1 Is he/she clumsy? A2 Is he/she fumbling? A3 Does he/she have balance problems? A4 Does he/she easily stumble and fall? A5 Have the peculiarities or problems relating to motor control caused significant impairment in school, among peers or at home? A6 Do the peculiarities or problems relating to motor control cause him/her significant suffering? A7 At what age did the peculiarities or problems relating to motor control commence? Age:

A8
Are they still present? Yes No

B. Perception
The essential aspect of each question is whether the problem/peculiarity has been pronounced compared to peers during any period of life Yes Yes, to some extent No 2 Does he/she seem disturbed by height differences such as in connection with climbing stairs etc.? 3 Does he/she have difficulty judging distance or size? 4 Is he/she oversensitive to touch or tight clothing? 5 Is he/she particularly sensitive to certain sounds/noise? 6 Is he/she particularly sensitive to certain flavours, smells, or consistencies?
If "Yes" or "Yes, to some extent" to any of these questions: B1 Does he/she have difficulty comprehending orientation and spatial directions, e. If "Yes" or "Yes, to some extent" to any of these questions: D1 Is he/she unusually intrepid in physically dangerous situations? D2 Have the peculiarities or problems relating to impulsiveness and activity caused significant impairment in school, among peers or at home? D3 Do the peculiarities or problems impulsiveness and activity cause him/her significant suffering? D4 At what age did the peculiarities or problems relating to impulsiveness and activity commence? Age:

D5
Are they still present?
Yes No

E. Learning
The essential aspect of each question is whether the problem/peculiarity has been pronounced compared to peers during any period of life If "Yes" or "Yes, to some extent" to any of these questions: E1 Is he/she a slow reader? E2 Does he/she dislike reading (e.g. does he/she avoid reading books)? E3 Does he/she have difficulties solving maths problems, which require him/her to read written material? E4 Does he/she have difficulties understanding or using abstract terms? E5 Does he/she have difficulties spelling? E6 Does he/she get special education in school? E7 Have peculiarities or problems relating to learning caused significant impairment in school, among peers or at home? E8 Do the peculiarities or problems relating to learning cause him/her significant suffering? E9 At what age did the peculiarities or problems relating to learning commence? Age: E10 Are they still present? Yes No

F. Planning and organizing tasks
The essential aspect of each question is whether the problem/peculiarity has been pronounced compared to peers during any period of life Have peculiarities or problems relating to planning and organizing tasks caused significant impairment in school, among peers or at home? F7 Do the peculiarities or problems relating to planning and organizing tasks cause him/her significant suffering? F8 At what age did the peculiarities or problems relating to planning and organizing tasks commence? Age:

F9
Are they still present? Yes No

G. Memory
The essential aspect of each question is whether the problem/peculiarity has been pronounced compared to peers during any period of life Have peculiarities or problems relating to social interaction caused significant impairment in school, among peers or at home? I17 Do the peculiarities or problems relating to social interaction cause him/her significant suffering? I18 At what age did the peculiarities or problems relating to social interaction commence? Age:

I19
Are they still present? Yes No

J. Flexibility
The essential aspect of each question is whether the problem/peculiarity has been pronounced compared to peers during any period of life Yes Yes, to some extent No 46 Does he/she get absorbed by his/her interests in such a way as being repetitive or too intense? 47 Does he/she get absorbed by routines in such a way as to produce problems for him/herself or others? 48 Has he/she ever engaged in strange hand movements or toe-walking when he/she was happy or upset? 49 Does he/she get obsessed with details? 50 Does he/she dislike changes in daily routines?
If "Yes" or "Yes, to some extent" to any of these questions: J1 Have peculiarities or problems relating to flexibility caused significant impairment in school, among peers or at home? J2 Do the peculiarities or problems relating to flexibility cause him/her significant suffering? J3 At what age did the peculiarities or problems relating to flexibility commence? Age:

J4
Are they still present? Yes No

K. Tics
The essential aspect of each question is whether the problem/peculiarity has been pronounced compared to peers during any period of life Does he/she make a lot of noise, e.g. whistle, hum, mumble?
If "Yes" or "Yes, to some extent" to any of these questions: K1 Does he/she curse or use dirty words in an exaggerated way? K2 Have peculiarities or problems relating to tics caused significant impairment in school, among peers or at home? K3 Do the peculiarities or problems relating to tics cause him/her significant suffering? K4 At what age did the peculiarities or problems relating to tics commence? Age:

K5
Are they still present? Yes No

L. Compulsions
The essential aspect of each question is whether the problem/peculiarity has been pronounced compared to peers during any period of life Has he/she ever failed to gain enough weight for more than a year or been underweight? 57 Has he/she appeared to be fearful of gaining weight or becoming fat?
If "Yes" or "Yes, to some extent" to any of these questions:

M1
Has he/she dieted hard enough to cause underweight or no weight gain for any length of time? M2 Has he/she exercised excessively or has he/she been overly interested in his/her physical appearance? M3 Females only: Has she failed to menstruate for at least 3 months due to weight loss? M4 Has he/she had periods of overeating followed by vomiting? M5 Has he/she ever tried to lose weight in spite of already being thin? M6 Has he/she ever had anorexia nervosa? M7 Have peculiarities or problems relating to eating caused significant impairment in school, among peers or at home? M8 Do the peculiarities or problems relating to eating cause him/her significant suffering? M9 At what age did the peculiarities or problems relating to eating commence? Age: M10 Are they still present? Yes No

N. Separations
The essential aspect of each question is whether the problem/peculiarity has been pronounced compared to peers during any period of life Does he/she complain about recurring headaches, bellyaches, nausea or vomiting after being separated from loved ones?
If "Yes" or "Yes, to some extent" to any of these questions: N1 Does he/she have difficulty leaving home to go to school for fear of being separated from his/her family? N2 Does he/she have recurring nightmares about being separated from the family? N3 Does he/she react unusually strongly when friendships or other close relationships come, or are about to come, to an end? N4 Have peculiarities or problems relating to separation caused significant impairment in school, among peers or at home? N5 Do the peculiarities or problems relating to separation cause him/her significant suffering? N6 At what age did the peculiarities or problems relating to separation commence? Age:

N7
Are they still present? Yes No

O+P. Defiance/Conduct
The essential aspect of each question is whether the problem/peculiarity has been pronounced compared to peers during any period of life Yes Yes, to some extent