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Proneness to infections and familial risk of tic disorders

Pol-Fuster, Josep ; Vasiljevic, Sara ; Fernández De La Cruz, Lorena ; Beucke, Jan C. ; Hesselmark, Eva ; Crowley, James J. ; Brikell, Isabell ; De Schipper, Elles ; D’Onofrio, Brian M. and Chang, Zheng , et al. (2026) In Psychological Medicine 56.
Abstract

Background Postinfectious autoimmune processes are hypothesized to be causally implicated in tic disorders, including Tourette syndrome and chronic tic disorder. However, this hypothesis remains controversial. In this nationwide cohort study, we aimed to clarify the mechanisms underlying the association between proneness to infections and tic disorders. Methods Using Swedish national registers, we identified 3,886,533 individuals (probands) born between 1970 and 2008 with available data on both biological parents. Probands were linked to six clusters of relatives: parents, full siblings, maternal half-siblings, paternal half-siblings, aunts/uncles, and cousins. Cox proportional hazards regression models were used to estimate the risk of... (More)

Background Postinfectious autoimmune processes are hypothesized to be causally implicated in tic disorders, including Tourette syndrome and chronic tic disorder. However, this hypothesis remains controversial. In this nationwide cohort study, we aimed to clarify the mechanisms underlying the association between proneness to infections and tic disorders. Methods Using Swedish national registers, we identified 3,886,533 individuals (probands) born between 1970 and 2008 with available data on both biological parents. Probands were linked to six clusters of relatives: parents, full siblings, maternal half-siblings, paternal half-siblings, aunts/uncles, and cousins. Cox proportional hazards regression models were used to estimate the risk of tic disorders in probands exposed to infections and their relatives, compared with unexposed probands and their relatives. We also examined dose–response associations using logistic regression models. Results Probands exposed to infections had an increased risk of tic disorders (hazard ratio [HR], 1.46; 95% confidence interval [CI], 1.40–1.52), as did their relatives. The observed risks increased with the degree of genetic relatedness, from HR (95% CI) of 1.15 (1.12–1.19) in cousins to 1.31 (1.25–1.37) in first-degree relatives. There was a dose–response association between the number of infections in the probands and the odds for tic disorders in the probands and their relatives. Results remained consistent after adjustment for infections in relatives, tic disorders in probands, and autoimmune diseases in probands and relatives. Conclusions Our results suggest an important role of shared genetic factors in the association between infections and tic disorders, potentially pointing to pleiotropic mechanisms.

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type
Contribution to journal
publication status
published
subject
keywords
chronic tic disorder, cohort study, familial co-aggregation study, infections, PANDAS, PANS, Tourette syndrome
in
Psychological Medicine
volume
56
article number
e108
publisher
Cambridge University Press
external identifiers
  • scopus:105036457143
  • pmid:42015626
ISSN
0033-2917
DOI
10.1017/S003329172610419X
language
English
LU publication?
yes
id
db0d58d3-f3aa-4683-8df3-8530c66d704e
date added to LUP
2026-05-21 15:03:10
date last changed
2026-06-18 17:22:39
@article{db0d58d3-f3aa-4683-8df3-8530c66d704e,
  abstract     = {{<p>Background Postinfectious autoimmune processes are hypothesized to be causally implicated in tic disorders, including Tourette syndrome and chronic tic disorder. However, this hypothesis remains controversial. In this nationwide cohort study, we aimed to clarify the mechanisms underlying the association between proneness to infections and tic disorders. Methods Using Swedish national registers, we identified 3,886,533 individuals (probands) born between 1970 and 2008 with available data on both biological parents. Probands were linked to six clusters of relatives: parents, full siblings, maternal half-siblings, paternal half-siblings, aunts/uncles, and cousins. Cox proportional hazards regression models were used to estimate the risk of tic disorders in probands exposed to infections and their relatives, compared with unexposed probands and their relatives. We also examined dose–response associations using logistic regression models. Results Probands exposed to infections had an increased risk of tic disorders (hazard ratio [HR], 1.46; 95% confidence interval [CI], 1.40–1.52), as did their relatives. The observed risks increased with the degree of genetic relatedness, from HR (95% CI) of 1.15 (1.12–1.19) in cousins to 1.31 (1.25–1.37) in first-degree relatives. There was a dose–response association between the number of infections in the probands and the odds for tic disorders in the probands and their relatives. Results remained consistent after adjustment for infections in relatives, tic disorders in probands, and autoimmune diseases in probands and relatives. Conclusions Our results suggest an important role of shared genetic factors in the association between infections and tic disorders, potentially pointing to pleiotropic mechanisms.</p>}},
  author       = {{Pol-Fuster, Josep and Vasiljevic, Sara and Fernández De La Cruz, Lorena and Beucke, Jan C. and Hesselmark, Eva and Crowley, James J. and Brikell, Isabell and De Schipper, Elles and D’Onofrio, Brian M. and Chang, Zheng and Larsson, Henrik and Tedroff, Kristina and Lichtenstein, Paul and Kuja-Halkola, Ralf and Idring, Selma and Mataix-Cols, David}},
  issn         = {{0033-2917}},
  keywords     = {{chronic tic disorder; cohort study; familial co-aggregation study; infections; PANDAS; PANS; Tourette syndrome}},
  language     = {{eng}},
  publisher    = {{Cambridge University Press}},
  series       = {{Psychological Medicine}},
  title        = {{Proneness to infections and familial risk of tic disorders}},
  url          = {{http://dx.doi.org/10.1017/S003329172610419X}},
  doi          = {{10.1017/S003329172610419X}},
  volume       = {{56}},
  year         = {{2026}},
}