Genetics of early-onset Parkinson's disease in Finland: exome sequencing and genome-wide association study.

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 early-onset 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.

journal_name

Neurobiol Aging

journal_title

Neurobiology of aging

authors

Siitonen A,Nalls MA,Hernández D,Gibbs JR,Ding J,Ylikotila P,Edsall C,Singleton A,Majamaa K

doi

10.1016/j.neurobiolaging.2017.01.019

subject

Has Abstract

pub_date

2017-05-01 00:00:00

pages

195.e7-195.e10

eissn

0197-4580

issn

1558-1497

pii

S0197-4580(17)30027-1

journal_volume

53

pub_type

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