Analysis of Genome-Wide Association Studies of Alzheimer Disease and of Parkinson Disease to Determine If These 2 Diseases Share a Common Genetic Risk

作者：Moskvina Valentina^*; Harold Denise; Russo GianCarlo; Vedemikov Alexey; Sharma Manu; Saad Mohamad; Holmans Peter; Bras Jose M; Bettella Francesco; Keller Margaux F; Nicolaou Nayia; Simon Sanchez Javier; Gibbs J Raphael; Schulte Claudia; Durr Alexandra; Guerreiro Rita; Hernandez Dena; Brice Alexis; Stefansson Hreinn; Majamaa Kari; Gasser Thomas; Heutink Peter; Wood Nick; Martinez Maria; Singleton Andrew B; Nalls Michael A; Hardy John; Owen Michael J; O&apos

来源：JAMA Neurology, 2013, 70(10): 1268-1276.

DOI：10.1001/jamaneurol.2013.448

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. %26lt;br%26gt;OBJECTIVE To assess the genetic overlap between PD and AD by testing for the presence of potentially pleiotropic loci in 2 recent GWA studies of PD and AD. %26lt;br%26gt;DESIGN Combined GWA analysis. %26lt;br%26gt;SETTING Data sets from the United Kingdom, Germany, France, and the United States. %26lt;br%26gt;PARTICIPANTS Thousands of patients with AD or PD and their controls. %26lt;br%26gt;MAIN OUTCOMES AND MEASURES Meta-analysis of GWA studies of AD and PD. %26lt;br%26gt;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. %26lt;br%26gt;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. %26lt;br%26gt;CONCLUSION AND RELEVANCE Our findings therefore imply that loci that increase the risk of both PD and AD are not widespread and that the pathological overlap could instead be %26quot;downstream%26quot; of the primary susceptibility genes that increase the risk of each disease.

• 出版日期2013-10