A1 Vertaisarvioitu alkuperäisartikkeli tieteellisessä lehdessä
Genetics of early-onset Parkinson's disease in Finland: exome sequencing and genome-wide association study
Tekijät: Siitonen A, Nalls MA, Hernandez D, Gibbs JR, Ding JH, Ylikotila P, Edsall C, Singleton A, Majamaa K
Kustantaja: ELSEVIER SCIENCE INC
Julkaisuvuosi: 2017
Journal: Neurobiology of Aging
Tietokannassa oleva lehden nimi: NEUROBIOLOGY OF AGING
Lehden akronyymi: NEUROBIOL AGING
Artikkelin numero: ARTN 195.e7
Vuosikerta: 53
Sivujen määrä: 4
ISSN: 0197-4580
eISSN: 1558-1497
DOI: https://doi.org/10.1016/j.neurobiolaging.2017.01.019
Tiivistelmä
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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