1. ¹Indiana University School of Medicine, Indianapolis, IN, USA
2. ²INSERM EMI00-06, 523 Place des Terrasses de l'Agora, Evry, France

Correspondence: Dr T Foroud, Department of Medical and Molecular Genetics (IB 130), Indiana University School of Medicine, 975 West Walnut Street, Indianapolis, IN 46202-5251, USA. Tel: +1 317 278 1291; Fax: +1 317 278 1100; E-mail: tforoud@iupui.edu

³For more details regarding PROGENI/GSPD-European Consortium see Appendix A.

Received 14 February 2006; Revised 26 April 2006; Accepted 27 April 2006; Published online 31 May 2006.

Abstract

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 80 cM 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).