title: Enrichment of Minor Alleles of Common SNPs and Improved Risk Prediction for Parkinson's Disease.
abstract: Parkinson disease (PD) is the second most common neurodegenerative disorder in the aged population and thought to involve many genetic loci. While a number of individual single nucleotide polymorphisms (SNPs) have been linked with PD, many remain to be found and no known markers or combinations of them have a useful predictive value for sporadic PD cases. The collective effects of genome wide minor alleles of common SNPs, or the minor allele content (MAC) in an individual, have recently been shown to be linked with quantitative variations of numerous complex traits in model organisms with higher MAC more likely linked with lower fitness. Here we found that PD cases had higher MAC than matched controls. A set of 37564 SNPs with MA (MAF < 0.4) more common in cases (P < 0.05) was found to have the best predictive accuracy. A weighted risk score calculated by using this set can predict 2% of PD cases (100% specificity), which is comparable to using familial PD genes to identify familial PD cases. These results suggest a novel genetic component in PD and provide a useful genetic method to identify a small fraction of PD cases.
authors.affiliation: State Key Laboratory of Medical Genetics, Central South University, 110 Xiangya Road, Changsha, Hunan, 410078, China.
authors.forename: Zuobin
authors.initials: Z
authors.lastname: Zhu
authors.affiliation: State Key Laboratory of Medical Genetics, Central South University, 110 Xiangya Road, Changsha, Hunan, 410078, China.
authors.forename: Dejian
authors.initials: D
authors.lastname: Yuan
authors.affiliation: State Key Laboratory of Medical Genetics, Central South University, 110 Xiangya Road, Changsha, Hunan, 410078, China.
authors.forename: Denghui
authors.initials: D
authors.lastname: Luo
authors.affiliation: State Key Laboratory of Medical Genetics, Central South University, 110 Xiangya Road, Changsha, Hunan, 410078, China.
authors.forename: Xitong
authors.initials: X
authors.lastname: Lu
authors.affiliation: State Key Laboratory of Medical Genetics, Central South University, 110 Xiangya Road, Changsha, Hunan, 410078, China.
authors.forename: Shi
authors.initials: S
authors.lastname: Huang
mesh_terms: D000483:Alleles; D016022:Case-Control Studies; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D005838:Genotype; D006801:Humans; D010300:Parkinson Disease / Q000453:epidemiology* / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D012306:Risk