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

Hum Genet. 2006 Mar;119(1-2):51-60. doi: 10.1007/s00439-005-0108-7. Epub 2005 Dec 14.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Age of Onset
  • Chromosome Mapping
  • Chromosomes, Human, Pair 14
  • Chromosomes, Human, Pair 9
  • Female
  • Gene Frequency
  • Genetic Predisposition to Disease / genetics*
  • Genetics, Population
  • Genome, Human
  • Haplotypes / genetics
  • Humans
  • Male
  • Microsatellite Repeats
  • Netherlands / epidemiology
  • Odds Ratio
  • Parkinson Disease / epidemiology
  • Parkinson Disease / genetics*
  • Pedigree
  • alpha-Synuclein / genetics

Substances

  • alpha-Synuclein