Parkinson disease (PD) is the second most common neurodegenerative disorder. Despite the identification of five causative genes, the majority of PD etiology is still unknown. A region on chromosome 5q is one of the few regions of the genome found linked in multiple studies of familial PD. Analyses were performed using genotypic data from two independent research studies to evaluate rigorously the evidence of linkage on chromosome 5. The combined sample consisting of 1238 affected individuals from 569 multiplex PD families were genotyped for a common set of 20 microsatellite markers spanning an 80cM region on chromosome 5q. Two disease models were employed and model-free linkage analyses were performed to detect linkage to a PD susceptibility gene and also to detect linkage to a quantitative phenotype, age of onset of PD. There was little evidence of linkage using either a narrower or broader disease definition (lod <0.5). Analyses employing age of onset of PD as the phenotype produced a lod score of 1.8. These results in a very large sample of familial PD suggest that it is unlikely that a PD susceptibility gene is located on chromosome 5q. Evidence for a locus contributing to the age of onset of PD is modest at best (empirical P-value=0.07).
Bibliographical noteFunding Information:
This project was supported by NS37167 (to TF) and the Michael J Fox Foundation for Parkinson’s Research, Edmond J Safra Global Genetics Consortia (to TF, MM and NW). This work was also supported by grants from the European Community Biomed 2 (BMHCT960664), National Institutes of Health (Grant NS41723-01A1 to AB), the Parkinson’s disease society and the Brain Research Trust (to NW), BMBF (Grant No. 01 GI 0201, Kompetenznetzwerk Parkinson to TG), the National Network for Genome Research (Grant No. 01 GS0116 to TG), ‘Ministero dell’Istruzione, Universita’ e Ricerca’, MIUR, Italy (to GM and VB), the NINDS Udall Center (to JH and MF), the NIA intramural program (JH) and NIH/NINDS P01 NS40256 (MF). We thank the members of the French Parkinson’s Disease Genetic Study Group for contributing to the recruitment of families.
- Chromosome 5
- Linkage analysis
- Parkinson disease