Aug 5, 2013

Alzheimer's and Parkinson Disease Do Not Share Common Genetic Risk

A study by Valentina Moskvina, Ph.D., of the Cardiff University School of Medicine and colleagues, examined the genetic overlap between Parkinson disease (PD) and Alzheimer disease (AD).

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Alzheimer's and Parkinson Disease Do Not Share Common Genetic Risk

Importance

Despite Alzheimer disease (AD) and Parkinson disease (PD) being clinically distinct entities, there is a possibility of a pathological overlap, with some genome-wide association (GWA) studies suggesting that the 2 diseases represent a biological continuum.

The application of GWA studies to idiopathic forms of AD and PD have identified a number of loci that contain genetic variants that increase the risk of these disorders.

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Alzheimer Disease and Parkinson Disease Do Not Appear To Share Common Genetic Risk, Study Suggests

Objective

To assess the genetic overlap between PDand AD by testing for the presence of potentially pleiotropic loci in 2 recent GWA studies of PD and AD.

Participants

Thousands of patients with AD or PD and their controls.

Main Outcome and Measures

Meta-analysis of GWA studies of AD and PD.

Methods

To identify evidence for potentially pleiotropic alleles that increased the risk for both PD and AD, we performed a combined PD-AD meta-analysis and compared the results with those obtained in the primary GWA studies.

We also tested for a net effect of potentially polygenic alleles that were shared by both disorders by performing a polygenic score analysis.

Finally, we also performed a gene-based association analysis that was aimed at detecting genes that harbor multiple disease-causing single-nucleotide polymorphisms, some of which confer a risk of PD and some a risk of AD.

Results

Detailed interrogation of the single-nucleotide polymorphism, polygenic, and gene-based analyses resulted in no significant evidence that supported the presence of loci that increase the risk of both PD and AD.


JAMA Neurol. doi:10.1001/jamaneurol.2013.448 Published online August 5, 2013.

Data sets from the United Kingdom, Germany, France and the United States were used to perform a combined genome-wide association analysis (GWA). The GWA study of AD included 3,177 patients with AD and 7,277 control patients, and the GWA analysis for PD included 5,333 patients with PD and 12,298 control patients. The gene-based analyses resulted in no significant evidence that supported the presence of loci (location of gene) that were associated with increased risk for both PD and AD, according to the study results.

Note: This study was supported by Parkinson’s United Kingdom, the Medical Research Council, and numerous other funding sources. Please see the articles for additional information, including other authors, author contributions and affiliations, financial disclosures, funding and support, etc.

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