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Enrichment of Minor Alleles of Common SNPs and Improved Risk Prediction for Parkinson's Disease.

Zhu Z, Yuan D, Luo D, Lu X, Huang S - PLoS ONE (2015)

Bottom Line: 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.These results suggest a novel genetic component in PD and provide a useful genetic method to identify a small fraction of PD cases.

View Article: PubMed Central - PubMed

Affiliation: State Key Laboratory of Medical Genetics, Central South University, 110 Xiangya Road, Changsha, Hunan, 410078, China.

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.

No MeSH data available.


Related in: MedlinePlus

Distribution of MAC and genetic risk allele scores of MAs by case–control status.MAC: Minor allele content of SNPs with MAF < 0.4. Genetic risk score, the total risk score of all the MAs in an individual by adding the coefficient of logistic regression test of each MA.
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pone.0133421.g001: Distribution of MAC and genetic risk allele scores of MAs by case–control status.MAC: Minor allele content of SNPs with MAF < 0.4. Genetic risk score, the total risk score of all the MAs in an individual by adding the coefficient of logistic regression test of each MA.

Mentions: SNPs typically have just two alleles in a population and the minor allele (MA) has frequency (MAF) <0.5. Here we calculated the minor allele content of each individual with MA defined as those with MAF < 0.4 in a control population. SNPs with MAF >0.4 and <0.5 were not considered in order to be more certain about the MA status. Using the control population of the phs000196.v2.p1 dataset, we obtained the MA status of each SNP and calculated the MAC of each individual control and case. We found that PD cases had higher average MAC than the controls (p = 4E-09, one-way ANOVA) (S2 Table). To confirm this finding, we examined a second case control dataset phs000394.v1.p1. From the control population in the second dataset, we obtained the MA status of each SNP and calculated the MAC of each individual control and case. Again, cases were found to have higher average MAC than the controls (p = 1E-08, one-way ANOVA) (S2 Table). For both datasets, the MAC was both normally distributed with the distribution of cases slightly shifted to the right or higher MAC position (Fig 1A and 1B).


Enrichment of Minor Alleles of Common SNPs and Improved Risk Prediction for Parkinson's Disease.

Zhu Z, Yuan D, Luo D, Lu X, Huang S - PLoS ONE (2015)

Distribution of MAC and genetic risk allele scores of MAs by case–control status.MAC: Minor allele content of SNPs with MAF < 0.4. Genetic risk score, the total risk score of all the MAs in an individual by adding the coefficient of logistic regression test of each MA.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4514478&req=5

pone.0133421.g001: Distribution of MAC and genetic risk allele scores of MAs by case–control status.MAC: Minor allele content of SNPs with MAF < 0.4. Genetic risk score, the total risk score of all the MAs in an individual by adding the coefficient of logistic regression test of each MA.
Mentions: SNPs typically have just two alleles in a population and the minor allele (MA) has frequency (MAF) <0.5. Here we calculated the minor allele content of each individual with MA defined as those with MAF < 0.4 in a control population. SNPs with MAF >0.4 and <0.5 were not considered in order to be more certain about the MA status. Using the control population of the phs000196.v2.p1 dataset, we obtained the MA status of each SNP and calculated the MAC of each individual control and case. We found that PD cases had higher average MAC than the controls (p = 4E-09, one-way ANOVA) (S2 Table). To confirm this finding, we examined a second case control dataset phs000394.v1.p1. From the control population in the second dataset, we obtained the MA status of each SNP and calculated the MAC of each individual control and case. Again, cases were found to have higher average MAC than the controls (p = 1E-08, one-way ANOVA) (S2 Table). For both datasets, the MAC was both normally distributed with the distribution of cases slightly shifted to the right or higher MAC position (Fig 1A and 1B).

Bottom Line: 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.These results suggest a novel genetic component in PD and provide a useful genetic method to identify a small fraction of PD cases.

View Article: PubMed Central - PubMed

Affiliation: State Key Laboratory of Medical Genetics, Central South University, 110 Xiangya Road, Changsha, Hunan, 410078, China.

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.

No MeSH data available.


Related in: MedlinePlus