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Genetic maternal effects contributes to the risk of Tourette's disorder

By Behrang Mahjani, Lambertus Klei, Christina M. Hultman, Henrik Larsson, Sven Sandin, Bernie Devlin, Joseph D. Buxbaum, Dorothy E. Grice

Posted 02 Dec 2020
medRxiv DOI: 10.1101/2020.11.30.20240598

Background: Risk for Tourette's and related tic disorders (CTD) derives from a combination of genetic and environmental factors. While multiple studies have demonstrated the importance of direct additive genetic variation for CTD, little is known about the role of cross-generational transmission of genetic risks, such as maternal effects. Here, we partition sources of variation on CTD risk into direct additive genetic effect and maternal effects. Methods: The study population consists of 2,522,677 individuals from the Swedish Medical Birth Register, born in Sweden between January 1, 1982, to December 31, 1990, and followed for a diagnosis of CTD through December 31, 2013. Results: We identified 6,227 (0.25%) individuals in the birth cohort diagnosed with CTD. Using generalized linear mixed models, we estimated 4.7% (95% CrI, 4.4%-4.8%) genetic maternal effects, 0.5% (95% CrI, 0.2%-7%) environmental maternal effects, and 61% (95% CrI, 59%-63%) direct additive genetic effects. Around 1% of genetic maternal effects were due to maternal effects from the individual with comorbid obsessive-compulsive disorder. Conclusions: Our results demonstrate genetic maternal effects contributing to the risk of CTD in offspring and also highlight new sources of overlapping risk between CTD and obsessive-compulsive disorder.

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