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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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