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

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 (Z lr = 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 (Z lr = 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.