Thesis defence in the University of Oulu

Doctoral Candidate

Master of science Susanna Ylönen

Faculty and research unit

University of Oulu Graduate School, Faculty of Medicine, Research Unit of Clinical Neuroscience

Field of study

Neurology

Date and time of the thesis defence

15.11.2019 12:00

Place of the thesis defence

Auditorium 8 of Oulu University Hospital (Kajaanintie 50)

Topic of the dissertation

Genetic risk factors for movement disorders in Finland

Opponent

Docent Annakaisa Haapasalo, University of Eastern Finland

Custos

Professor Kari Majamaa, University of Oulu

Genetic risk factors for movement disorders in Finland

In this study, genetic risk factors for Parkinson’s disease and Huntington’s disease were investigated in Finnish patients.

Parkinson’s disease and Huntington’s disease are neurodegenerative movement disorders that usually manifest in the adulthood. Parkinson’s disease affects about one percent of people older than 60 years, and the number of patients is expected to rise due to the increased life expectancy in the population. Huntington’s disease is rare with the frequency of 2/100 000 in the Finnish population.

We investigated 852 patients with Parkinson’s disease that had either early-onset or late-onset Parkinson’s disease. Genetic variants that predispose to Parkinson’s disease were found in POLG1 and GBA genes, whereas certain risk factors found in European patients were not detected. Four patients harbored more than one variant in POLG1. In addition, Parkinson’s disease was more often detected in the siblings of patients with POLG1 variants. The CAG repeat length variation in POLG1 was associated with the risk of Parkinson’s disease. Similarly, a variant in the GBA gene was detected, that was found to significantly increase the risk of Parkinson’s disease.

Huntington’s disease is caused by an expansion of a CAG repeat in the HTT gene beyond a critical threshold length. There were 225 patients with Huntington’s disease in the study. We investigated genetic factors involved in the length and expansion of the repeat.

The frequency of haplogroup A in the HTT gene was lower than in other European populations. Haplogroup A was significantly more common in patients than in population controls. The CAG repeat number increased by 3.18 repeats on average when inherited from the father and 0.11 repeats when inherited from the mother in patients with the HTT haplogroup A. When haplogroup C was involved, the CAG repeat tended to contract slightly in both maternal and paternal transmissions.

Huntington’s disease is less common in Finland than in other European populations. According to this study, this is explained by the fact that the predisposing haplogroup A is less frequent in the Finnish population. The HTT haplogroup was found to affect the intergenerational changes in the length of the CAG repeat.

The Finnish population is different from other European populations due to the population history. Genetic research generates understanding for the causes of diseases. This helps in developing medications and treatments. Same diseases can have different genetic risk factors in diverse genetic backgrounds. Therefore, it is necessary to investigate causes of diseases in different populations. This makes it possible to target genetic testing to variants that are likely to occur in the population.

Dissertation

Last updated: 8.11.2019