Familial liability to asthma and ADHD: A Swedish national register-based study

Shihua Sun; Ralf Kuja-Halkola; Zheng Chang; Samuele Cortese; Catarina Almqvist; Henrik Larsson

doi:10.1002/jcv2.12044

Familial liability to asthma and ADHD: A Swedish national register-based study

JCPP Adv. 2021 Oct 23;1(4):e12044. doi: 10.1002/jcv2.12044. eCollection 2021 Dec.

Authors

Shihua Sun¹, Ralf Kuja-Halkola¹, Zheng Chang¹, Samuele Cortese², Catarina Almqvist^{1

3}, Henrik Larsson^{1

4}

Affiliations

¹ Department of Medical Epidemiology and Biostatistics Karolinska Institutet Stockholm Sweden.
² Center for Innovation in Mental Health Academic Unit of Psychology University of Southampton Southampton UK.
³ Pediatric Allergy and Pulmonology Unit at Astrid Lindgren Children's Hospital Karolinska University Hospital Solna Sweden.
⁴ School of Medical Sciences Örebro University Örebro Sweden.

Abstract

Background: Studies have reported significant associations between asthma and attention-deficit/hyperactivity disorder (ADHD), but whether the association is due to shared etiology such as shared genetic risk factors remains unclear. We aimed to investigate patterns of familial co-aggregation of asthma and ADHD and also to quantify the relative contribution of genetic and environmental influences.

Methods: Through Swedish register linkages, we obtained a cohort of 927,956 individuals born 1992-2001 and identified monozygotic twins (MZ), dizygotic twins (DZ), full- and half-siblings, and full- and half-cousins. Clinical diagnosis of asthma and ADHD were identified from the Swedish national registers. We used logistic regressions to investigate the within-individual association and familial co-aggregation between asthma and ADHD. We then used bivariate twin modeling to quantify the genetic and environmental correlations and their contributions to the familial liability.

Results: Individuals with asthma had significantly higher risk of ADHD (odds ratio [OR], 1.50; 95% confidence interval [CI], 1.47-1.54). Relatives of individuals with asthma had an increased risk of ADHD compared to relatives of individuals without asthma; in familial co-aggregation analysis, the association was strongest in MZ twins (OR, 1.67; 95% CI, 0.99-2.84) and attenuated with degree of genetic relatedness. In the twin modeling, the phenotypic and genetic correlations between asthma and ADHD estimated from the ACE model were 0.09 (95% CI, 0.05-0.14) and 0.12 (95% CI, 0.02-0.21), respectively. The bivariate heritability was 0.88 (95% CI, 0.30-1.46). Estimates for contributions from shared and non-shared environment factors were not statistically significant.

Conclusions: Asthma and ADHD co-aggregate in families primarily due to shared genetic risk factors. Within-individual and family history of either disorder should prompt clinical assessment of the other condition. Future studies should further investigate genetic variants underlying the co-occurrence of ADHD and asthma.

Keywords: ADHD; asthma; family co‐aggregation; twin modeling.