Evidence for novel loci for late-onset Parkinson's disease in a genetic isolate from the Netherlands

We studied patients with idiopathic Parkinson's disease (PD) from an isolated population in the Netherlands aiming to map gene(s) involved in PD susceptibility. A total of 109 parkinsonism patients were independently ascertained, of whom 62 presented late-onset, idiopathic PD. Genealogical rese...

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Bibliographic Details
Published in:Human genetics 2006-03, Vol.119 (1-2), p.51-60
Main Authors: Bertoli-Avella, Aida M, Dekker, Marieke C J, Aulchenko, Yurii S, Houwing-Duistermaat, Jeanine J, Simons, Erik, Testers, Leon, Pardo, Luba M, Rademaker, Tessa A M, Snijders, Pieter J L M, van Swieten, John C, Bonifati, Vincenzo, Heutink, Peter, van Duijn, Cornelia M, Oostra, Ben A
Format: Article
Language:English
Subjects:
Age of Onset
alpha-Synuclein - genetics
Chromosome Mapping
Chromosomes
Chromosomes, Human, Pair 14
Chromosomes, Human, Pair 9
Female
Gene Frequency
Genes
Genetic Predisposition to Disease - genetics
Genetics, Population
Genome, Human
Genomes
Genomics
Haplotypes - genetics
Humans
Male
Microsatellite Repeats
Netherlands - epidemiology
Odds Ratio
Parkinson Disease - epidemiology
Parkinson Disease - genetics
Parkinson's disease
Pedigree
Population
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Summary:We studied patients with idiopathic Parkinson's disease (PD) from an isolated population in the Netherlands aiming to map gene(s) involved in PD susceptibility. A total of 109 parkinsonism patients were independently ascertained, of whom 62 presented late-onset, idiopathic PD. Genealogical research showed that 45 index cases with idiopathic PD were linked to a common ancestor, indicating familiar clustering among the patients. This strong familial clustering was highly significant (P = 0.005) when compared to random controls from the same population. We performed a genome wide scan using 382 polymorphic markers in 44 distantly related PD patients plus 112 unaffected first-degree relatives and spouses. Our genome wide association analysis (DISLAMB) revealed evidence of association at a nominal P-value < 0.01 for markers D2S2333, D4S405, D9S158, D13S153. Other regions on chromosomes 3p, 4q, 14q, 17p and 17q were found at a significance level of P < 0.05. In a follow-up study, we investigated all the positive regions using a denser marker set and a larger sample (total of 630 individuals including all late-onset PD patients). The strongest evidence for association remained for the 9q and 14q region. A significant association was found for marker D9S1838 (OR = 2.0, 95% CI 1.1-3.5, P = 0.014) and D14S65 (OR = 3.2, 95% CI 1.7-6.1, P < 0.001). Moreover, a common haplotype with excess of sharing among late-onset PD cases was observed on both regions. Our results suggest the existence of two loci influencing PD susceptibility on chromosome 9q and 14q.
ISSN:0340-6717
1432-1203
DOI:10.1007/s00439-005-0108-7