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Familial co-aggregation of attention-deficit/hyperactivity disorder and autoimmune diseases: a cohort study based on Swedish population-wide registers
Department of Biomedicine, University of Bergen, Bergen, Norway; Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
Department of Global Public Health and Primary Care, University of Bergen, Bergen, Norway; Division of Mental and Physical Health, Norwegian Institute of Public Health, Bergen, Norway.
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2022 (English)In: International Journal of Epidemiology, ISSN 0300-5771, E-ISSN 1464-3685, Vol. 51, no 3, p. 898-909Article in journal (Refereed) Published
Abstract [en]

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.

Place, publisher, year, edition, pages
Oxford University Press, 2022. Vol. 51, no 3, p. 898-909
Keywords [en]
Attention-deficit/hyperactivity disorder, autoimmunity, cohort study, familial aggregation, familial co-aggregation, genetics, maternal immune activation, national register, neurodevelopmental disorder
National Category
Psychiatry
Identifiers
URN: urn:nbn:se:oru:diva-93627DOI: 10.1093/ije/dyab151ISI: 000756670100001PubMedID: 34379767Scopus ID: 2-s2.0-85132846730OAI: oai:DiVA.org:oru-93627DiVA, id: diva2:1585020
Funder
Swedish Research Council, 2017-00788 2014-3831Fredrik och Ingrid Thurings Stiftelse, 2016-00254The Swedish Brain Foundation, FO2018-0273EU, Horizon 2020, 667302
Note

Funding agency:

Stiftelsen Kristian Gerhard Jebsen

University of Bergen

Western Norway Regional Health Authorities

Swedish Initiative for Research onMicrodata in the Social And Medical Sciences (SIMSAM) framework 340-2013-5867

Strategic Research Programme in Neuroscience (StratNeuro) of Karolinska Institutet

Available from: 2021-08-16 Created: 2021-08-16 Last updated: 2023-12-08Bibliographically approved

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