A1 Refereed original research article in a scientific journal
Genetics of early-onset Parkinson's disease in Finland: exome sequencing and genome-wide association study
Authors: Siitonen A, Nalls MA, Hernandez D, Gibbs JR, Ding JH, Ylikotila P, Edsall C, Singleton A, Majamaa K
Publisher: ELSEVIER SCIENCE INC
Publication year: 2017
Journal: Neurobiology of Aging
Journal name in source: NEUROBIOLOGY OF AGING
Journal acronym: NEUROBIOL AGING
Article number: ARTN 195.e7
Volume: 53
Number of pages: 4
ISSN: 0197-4580
eISSN: 1558-1497
DOI: https://doi.org/10.1016/j.neurobiolaging.2017.01.019(external)
Abstract
Several genes and risk factors are associated with Parkinson's disease (PD). Although many of the genetic markers belong to a common pathway, a unifying pathogenetic mechanism is yet to be found. Also, missing heritability analyses have estimated that only part of the genetic influence contributing to PD has been found. Here, we carried out whole-exome sequencing (WES) on 438 Finnish patients with earlyonset PD. We also reanalyzed previous data from genome-wide association studies (GWAS) on the same cohort. Variants in the CEL gene/locus were associated with PD in both GWAS and WES analysis. Exome-wide gene-based association tests also identified the MPHOSPH10, TAS2R19, and SERPINA1 genes in the discovery data set (p < 2.5E-6). MPHOSPH10 had estimated odds ratio (OR) of 1.53, and the rs141620200 variant in SERPINA1 had OR of 1.27. We identified several candidate genes, but further investigation is required to determine the role of these genes in PD. (C) 2017 Elsevier Inc. All rights reserved.
Several genes and risk factors are associated with Parkinson's disease (PD). Although many of the genetic markers belong to a common pathway, a unifying pathogenetic mechanism is yet to be found. Also, missing heritability analyses have estimated that only part of the genetic influence contributing to PD has been found. Here, we carried out whole-exome sequencing (WES) on 438 Finnish patients with earlyonset PD. We also reanalyzed previous data from genome-wide association studies (GWAS) on the same cohort. Variants in the CEL gene/locus were associated with PD in both GWAS and WES analysis. Exome-wide gene-based association tests also identified the MPHOSPH10, TAS2R19, and SERPINA1 genes in the discovery data set (p < 2.5E-6). MPHOSPH10 had estimated odds ratio (OR) of 1.53, and the rs141620200 variant in SERPINA1 had OR of 1.27. We identified several candidate genes, but further investigation is required to determine the role of these genes in PD. (C) 2017 Elsevier Inc. All rights reserved.
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