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Genetic and environmental correlates of Tourette Syndrome

PhD ceremony:Mr M. (Mohamed) Abdulkadir
When:November 08, 2021
Supervisors:prof. dr. P.J. (Pieter) Hoekstra, prof. dr. Jay Tischfield
Co-supervisors:dr. A. (Andrea) Dietrich, dr. Gary Heiman
Where:Academy building RUG
Faculty:Medical Sciences / UMCG
Genetic and environmental correlates of Tourette Syndrome

Tourette Syndrome is a heritable neuropsychiatric disorder characterized by motor and vocal tics. Decades of research also implicate environmental factors in the occurrence of tics; most notable are complications during and around pregnancy. In this thesis I aimed to further our understanding of the genetic and environmental causes of tics. To this end, I have used data from the ongoing Tourette International Collaborative Genetics (TIC Genetics; study and data from the Avon Longitudinal Study of Parents and Children (ALSPAC). The TIC Genetics study is a large international multicenter study led by clinicians and researchers in the field of Tourette and the ALSPAC study is a population-based birth cohort designed to understand the environmental and genetic determinants of health and development.I found no evidence for the involvement of single genes in tics but rather that an aggregate score of many signals across the genome, a polygenic risk score, is associated with tics. I also found that tics along a spectrum from non-clinical to clinical levels share a similar genetic background. Regarding the environmental factors, I found that a cumulative score of pregnancy complications better captures risk for tics rather than single pregnancy complications. Furthermore, I studied the polygenic risk score and the pregnancy complications together and found that the analyses of both factors better capture the risk for tics compared to studying them separately. The studies in this thesis highlight the importance and benefits of studying environmental and genetic risk factors jointly in understanding the causes of tics.