A susceptibility gene for late‐onset idiopathic Parkinson's disease

AA Hicks, H Pétursson, T Jónsson… - Annals of Neurology …, 2002 - Wiley Online Library
AA Hicks, H Pétursson, T Jónsson, H Stefánsson, HS Jóhannsdóttir, J Sainz, ML Frigge
Annals of Neurology: Official Journal of the American Neurological …, 2002Wiley Online Library
Eight regions of the genome (PARK1‐8) have been implicated in autosomal dominant and
autosomal recessive forms of early‐onset Parkinson's disease. These forms constitute a few
of all cases. However, except for a haplotype in six families (PARK3), no study has
successfully mapped a gene or described mutations that contribute to the common late‐
onset Parkinson's disease. Some have even suggested that a genetic component does not
exist. We cross‐matched our nationwide genealogy database with a population‐based list of …
Abstract
Eight regions of the genome (PARK1‐8) have been implicated in autosomal dominant and autosomal recessive forms of early‐onset Parkinson's disease. These forms constitute a few of all cases. However, except for a haplotype in six families (PARK3), no study has successfully mapped a gene or described mutations that contribute to the common late‐onset Parkinson's disease. Some have even suggested that a genetic component does not exist. We cross‐matched our nationwide genealogy database with a population‐based list of Icelandic Parkinson's disease patients to search for families with more than one patient. We performed a genomewide scan on 117 patients and 168 of their unaffected relatives within 51 families using 781 microsatellite markers. Allele‐sharing, model‐independent analysis of the results showed linkage to a region on chromosome 1p32 with a logarithm of odds score of 3.9 (Zlr = 4.2). By increasing the information content with additional microsatellite markers in this region, we found that the logarithm of odds score increased to 4.9 (Zlr = 4.8). This result corresponds to an unadjusted p value of 1.0 × 10−6 and p < 0.005 after adjusting for a genomewide search. We designate this region PARK10. We therefore have successfully mapped, to genomewide significance, a susceptibility gene for late‐onset Parkinson's disease using multiple families drawn across a whole population. Identification of the susceptibility gene in this region may pave the way for a better understanding of the disease process, which, in turn, may lead to improved diagnostics and therapeutics.
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