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. 2021 Oct 12:8:1762-1768.
doi: 10.1016/j.toxrep.2021.10.008. eCollection 2021.

Replication of chromosomal loci involved in Parkinson's disease: A quantitative synthesis of GWAS

Dimitrios Rikos  1   2 , Vasileios Siokas  1 , Tatyana I Burykina  3 , Nikolaos Drakoulis  4 , Efthimios Dardiotis  1 , Elias Zintzaras  2   5
Affiliations

Replication of chromosomal loci involved in Parkinson's disease: A quantitative synthesis of GWAS

Dimitrios Rikos et al. Toxicol Rep. .

Abstract

Introduction: Parkinson's disease is a neurodegenerative disorder with a complex etiology coming from interactions between genetic and environmental factors. Research on Parkinson's disease genetics has been an effortful struggle, while new technologies and novel study designs served as indispensable boosters. Until now, 90 loci and 20 disease-causing gene mutations have been identified. In this study we describe a novel non-parametric approach to GWAS meta-analysis and its application in PD genetics.

Methods: A literature search was conducted to identify Genome-Wide Association Studies (GWAS) regarding Parkinson's disease. We applied predefined inclusion criteria and extracted the reported SNPs and their respective position and statistical significance. We divided all chromosomes in approximately equal genetic distance segments called bins and recorded the most significant SNP from each bin and each study and ranked them in terms of their p-value. Ranks from each bin were summed, averaged and added in a heterogeneity-based analysis using the METRADISC-XL software. Weighted and unweighted analysis was performed.

Results: Five-hundred and forty-three SNPs and their respective p-values from 15 studies were matched in their corresponding bins. The METRADISC-XL analysis resulted in 7 bins with a significant p-value. A bin on chromosome 4 where the SNCA gene is located found with genome-wide significant association with Parkinson's Disease.

Conclusion: This is the first time a non-parametric method is applied in GWAS meta-analysis. The results add some insight on the overall understanding of Parkinson's disease genetics and serve as a first step of further convergent analysis with Genome-wide linkage studies.

Keywords: GWAS; Heterogeneity; METRADISC-XL; Meta-analysis; Parkinson’s disease.

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Conflict of interest statement

The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Figures

None
Graphical abstract
Fig. 1
Fig. 1
Weighted (square) and unweighted (circle) significance level of the average ranks of 120 bins in size-adjusted chromosomes. Bins with significant p-value<0,05 are shown above the 0.05 (solid) reference line.
See this image and copyright information in PMC

References

    1. Tysnes O.B., Storstein A. Epidemiology of Parkinson’s disease. J. Neural Transm. (Vienna, Austria : 1996) 2017;124(8):901–905. - PubMed
    1. Dickson D.W. Neuropathology of Parkinson disease. Parkinsonism Relat. Disord. 2018;46(Suppl 1) S30-s3. - PMC - PubMed
    1. Deng H., Wang P., Jankovic J. The genetics of Parkinson disease. Ageing Res. Rev. 2018;42:72–85. - PubMed
    1. Li J., Y-f Guo, Pei Y., Deng H.-W. The impact of imputation on meta-analysis of genome-wide association studies. PLoS One. 2012;7(4) - PMC - PubMed
    1. Cao Y., Liao M., Huang X., Mo Z., Gao F. Meta-analysis of genome-wide linkage studies of atopic dermatitis. Dermatitis : contact, atopic, occupational. Drug. 2009;20(4):193–199. - PubMed

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