Parkinson's disease and parkinsonism are relatively common neurodegenerative disorders. This study aimed to assess potential genetic risk factors of haplotypes in genes associated with parkinsonism in a population in which endemic parkinsonism and atypical parkinsonism have recently been found. The genes ADH1C, EIF4G1, FBXO7, GBA, GIGYF2, HTRA2, LRRK2, MAPT, PARK2, PARK7, PINK1 PLA2G6, SNCA, UCHL1, and VPS35 were analyzed in 62 patients (P) and 69 age-matched controls from the researched area (C1). Variants were acquired by high-throughput sequencing using Ion Torrent workflow. As another set of controls, the whole genome sequencing data from 100 healthy non-related individuals from the Czech population were used (C2); the results were also compared with the Genome Project data (C3). We observed shared findings of four intron (rs11564187, rs36220738, rs200829235, and rs3789329) and one exon variant (rs33995883) in the LRRK2 gene in six patients. A comparison of the C1-C3 groups revealed significant differences in haplotype frequencies between ratio of 2.09 for C1, 1.65 for C2, and 6.3 for C3, and odds ratios of 13.15 for C1, 2.58 for C2, and 7.6 for C3 were estimated. The co-occurrence of five variants in the LRRK2 gene (very probably in haplotype) could be an important potential risk factor for the development of parkinsonism, even outside the recently described pedigrees in the researched area where endemic parkinsonism is present.

1st Faculty of Medicine Institute of Biology and Medical Genetics Charles University and General University Hospital Prague 128 00 Prague Czech Republic

2nd Faculty of Medicine Institute of Biology and Medical Genetics Charles University 150 06 Prague Czech Republic

Department of Mathematical Analysis and Applications of Mathematics Faculty of Science Palacky University 779 00 Olomouc Czech Republic

Department of Medical Genetics Faculty of Medicine and Dentistry Palacky University 779 00 Olomouc Czech Republic

Department of Medical Genetics University Hospital Olomouc 779 00 Olomouc Czech Republic

Department of Neurology Faculty of Medicine and Dentistry Palacky University 779 00 Olomouc Czech Republic

Department of Neurology University Hospital Olomouc 779 00 Olomouc Czech Republic

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Endemic parkinsonism: clusters, biology and clinical features