Familial co-aggregation of attention-deficit/hyperactivity disorder and autoimmune diseases: a cohort study based on Swedish population-wide registers. (11th August 2021)

• Record Type: Journal Article
• Authors: Hegvik, Tor-Arne; Chen, Qi; Kuja-Halkola, Ralf; Klungsøyr, Kari; Butwicka, Agnieszka; Lichtenstein, Paul; Almqvist, Catarina; Faraone, Stephen V; Haavik, Jan; Larsson, Henrik
• Is Part Of: International journal of epidemiology. Volume 51:Number 3(2022)
• Page Start: 898
• Page End: 909
• Publication Date: 2021-08-11
• Subjects: Attention-deficit/hyperactivity disorder -- neurodevelopmental disorder -- autoimmunity -- familial aggregation -- familial co-aggregation -- genetics -- cohort study -- national register -- maternal immune activation; Epidemiology -- Periodicals; 614.4
• DOI: 10.1093/ije/dyab151
• Languages: English
• ISSNs: 0300-5771

Abstract

Abstract: Background: Attention-deficit/hyperactivity disorder (ADHD) has been associated with several autoimmune diseases (AD), both within individuals and across relatives, implying common underlying genetic or environmental factors in line with studies indicating that immunological mechanisms are key to brain development. To further elucidate the relationship between ADHD and autoimmunity we performed a population-wide familial co-aggregation study. Methods: We linked Swedish national registries, defined a birth cohort with their biological relatives and identified individuals diagnosed with ADHD and/or 13 ADs. The cohort included 5 178 225 individuals born between 1960 and 2010, of whom 118 927 (2.30%) had been diagnosed with ADHD. We then investigated the associations between ADHD and ADs within individuals and across relatives, with logistic regression and structural equation modelling. Results: Within individuals, ADHD was associated with a diagnosis of any of the 13 investigated ADs (adjusted odds ratio (OR) =1.34, 95% confidence interval (CI) = 1.30-1.38) as well as several specific ADs. Familial co-aggregation was observed. For example, ADHD was associated with any of the 13 ADs in mothers (OR = 1.29, 95% CI = 1.26–1.32), fathers (OR = 1.14, 95% CI = 1.11–1.18), full siblings (OR = 1.19, 95% CI = 1.15–1.22), aunts (OR = 1.12, 95% CI = 1.10–1.15), uncles (OR = 1.07, 95% CI = 1.05–1.10) and cousins (OR = 1.04, 95% CI = 1.03–1.06). Still, the absolute risks of AD among those with ADHD were low. The genetic correlation between ADHD and a diagnosis of any of the investigated ADs was 0.13 (95% CI = 0.09–0.17) and the environmental correlation was 0.02 (95% CI = -0.03–0.06). Conclusions: We found that ADHD and ADs co-aggregate among biological relatives, indicating that the relationship between ADHD and autoimmune diseases may in part be explained by shared genetic risk factors. The patterns of familial co-aggregation of ADHD and ADs do not readily support a role of maternal immune activation in the aetiology of ADHD. The findings have implications for aetiological models of ADHD. However, screening for autoimmunity among individuals with ADHD is not warranted.