Alpha‐synuclein repeat variants and survival in Parkinson's disease

Abstract

Objectives To determine if alpha-synuclein REP1 genotypes are associated with survival in Parkinson’s disease. Methods Investigators from the Genetic Epidemiology of Parkinson’s Disease Consortium provided REP1 genotypes and baseline and follow-up clinical data for cases. The primary outcome was time to death. Cox proportional hazards regression models were used to assess the association of REP1 genotypes with survival. Results Twenty-one sites contributed data for 6,154 cases. There was no significant association between alpha-synuclein REP1 genotypes and survival in Parkinson’s disease. However, there was a significant association between REP1 genotypes and age at onset of PD (Hazard Ratio = 1.06, 95% Confidence Interval = 1.01–1.10, p value = 0.01). Conclusions In our large consortium study, alpha-synuclein REP1 genotypes were not associated with survival in Parkinson’s disease. Further studies of α–synuclein’s role in disease progression and long-term outcomes are needed.

Modelling idiopathic Parkinson disease as a complex illness can inform incidence rate in healthy adults: the PREDIGT score

“…Given the lesser likelihood for the initiation of a tissue response that promotes PD resulting from altered interactions between the subject's genome and exposome (which we postulate may be due to the protective effects of smoking), we entered the total value of 0.25 under factor I (i.e. we equated his possible tissue response(s) to that of a proband carrying a mutant GBA allele or an expanded, Rep1‐positive SNCA allele (Chung et al ., ); Table ).…”

A cumulative genetic risk score predicts progression in Parkinson's disease

“…The present study is, to our knowledge, the first to report on the association between clinical outcomes in PD and cumulative polygenic risk. Two previous studies concerned with genetic variability in the SNCA locus found evidence indicating an effect on UPDRS motor progression, yet no association with survival . One study used telephone interviews to assess motor and cognitive outcomes in patients who participated in an early GWAS of PD, but identified no single‐SNP associations passing a Bonferroni‐corrected significance threshold …”

Clinically meaningful parameters of progression and long-term outcome of Parkinson disease: An international consensus statement

“…This would make it possible to provide individualized prognostic information to patients soon after the diagnosis is established, and hopefully to improve outcome by addressing modifiable factors of disease progression. cognitive outcomes after the onset of PD symptoms in a second study examining 1098 cases [8], and c) had no influence on survival in a third study on 6154 cases from the GEO-PD consortium [9]. Polymorphisms in the SNCA and MAPT genes interact to influence the rate of progression of PD in its early stages [40].…”

“…At this juncture, it is largely unknown which factors influence PD progression or long-term outcomes. Recent reports suggest that the factors and biological processes that underlie disease pathogenesis may differ from those that determine its course [8,9]. Some of the factors contributing to disease progression may be modifiable.…”