Chromosome 5 and Parkinson disease

Area of Science:

• Genetics
• Neuroscience
• Medical Research

Background:

• Parkinson disease (PD) is a prevalent neurodegenerative disorder with largely unknown etiology.
• Previous studies suggested a potential PD susceptibility locus on chromosome 5q in familial cases.
• Identifying genetic factors is crucial for understanding PD pathogenesis.

Purpose of the Study:

• To rigorously evaluate the evidence for linkage of a PD susceptibility gene on chromosome 5q.
• To investigate linkage to a quantitative phenotype, specifically the age of onset in Parkinson disease.

Main Methods:

• Genotypic data from 1238 affected individuals across 569 multiplex Parkinson disease families were analyzed.
• Microsatellite markers across an 80 cM region on chromosome 5q were genotyped.
• Linkage analyses were performed using both disease-specific and model-free approaches, including age of onset.

Main Results:

• Little evidence of linkage was found for a PD susceptibility gene on chromosome 5q, regardless of disease definition (lod <0.5).
• Analysis of age of onset as a phenotype yielded a modest lod score of 1.8 (empirical P-value=0.07).
• These findings were based on a large sample size of familial Parkinson disease.

Conclusions:

• It is unlikely that a major Parkinson disease susceptibility gene resides on chromosome 5q.
• The evidence for a locus influencing age of onset of Parkinson disease on chromosome 5q is weak.
• Further research is needed to identify the genetic underpinnings of Parkinson disease.