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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.
摘要：
多个基因和危险因素与帕金森病(PD)相关。虽然许多遗传标记属于一个共同的途径，尚未找到统一的致病机制。此外，缺失的遗传力分析估计，仅发现了部分导致PD的遗传影响。这里,我们对438例芬兰早发性PD患者进行了全外显子组测序(WES).我们还重新分析了来自同一队列的全基因组关联研究（GWAS）的先前数据。在GWAS和WES分析中，CEL基因/基因座的变异与PD相关。基于外显子组基因的关联测试还在发现数据集中鉴定了MPHOSPH10、TAS2R19和SERPINA1基因(p<2.5E-6)。MPHOSPH10的估计比值比（OR）为1.53，而SERPINA1中的rs141620200变体的OR为1.27。我们确定了几个候选基因，但是需要进一步的研究来确定这些基因在PD中的作用。
