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. 2016 Jan:37:209.e1-209.e7.
doi: 10.1016/j.neurobiolaging.2015.09.014. Epub 2015 Sep 30.

Variants in GBA, SNCA, and MAPT influence Parkinson disease risk, age at onset, and progression

Albert A Davis  1 , Kristin M Andruska  1 , Bruno A Benitez  2 , Brad A Racette  3 , Joel S Perlmutter  4 , Carlos Cruchaga  5
Affiliations

Variants in GBA, SNCA, and MAPT influence Parkinson disease risk, age at onset, and progression

Albert A Davis et al. Neurobiol Aging. 2016 Jan.

Abstract

Multiple genetic variants have been linked to risk of Parkinson disease (PD), but known mutations do not explain a large proportion of the total PD cases. Similarly, multiple loci have been associated with PD risk by genome-wide association studies (GWAS). The influence that genetic factors confer on phenotypic diversity remains unclear. Few studies have been performed to determine whether the GWAS loci are also associated with age at onset (AAO) or motor progression. We used 2 PD case-control data sets (Washington University and the Parkinson's Progression Markers Initiative) to determine whether polymorphisms located at the GWAS top hits (GBA, ACMSD/TMEM163, STK39, MCCC1/LAMP3, GAK/TMEM175, SNCA, and MAPT) show association with AAO or motor progression. We found associations between single nucleotide polymorphisms at the GBA and MAPT loci and PD AAO and progression. These findings reinforce the complex genetic basis of PD and suggest that distinct genes and variants explain the genetic architecture of PD risk, onset, and progression.

Keywords: Age at onset; GBA; MAPT; Motor progression; Parkinson disease; SNCA.

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Figures

Figure 1
Figure 1. rs75548401 and multiple SNPs at the MAPT locus relate to age at onset
Kaplan-Meier survival curves for age at onset of Parkinson disease motor symptoms are shown for alleles of the GBA variant rs75548401 (a) and rs2942168 (b), a representative variant at the MAPT locus. Rs75548401: mean survival 62 vs 60 years. Hazard ratio: 0.7497 (0.509-0.9512), p=0.0126. Rs2942168: mean survival 61 vs. 62 vs. 67 years. Hazard ratio: 1.17 (1.007-1.36), p=0.0132.
Figure 1
Figure 1. rs75548401 and multiple SNPs at the MAPT locus relate to age at onset
Kaplan-Meier survival curves for age at onset of Parkinson disease motor symptoms are shown for alleles of the GBA variant rs75548401 (a) and rs2942168 (b), a representative variant at the MAPT locus. Rs75548401: mean survival 62 vs 60 years. Hazard ratio: 0.7497 (0.509-0.9512), p=0.0126. Rs2942168: mean survival 61 vs. 62 vs. 67 years. Hazard ratio: 1.17 (1.007-1.36), p=0.0132.
Figure 2
Figure 2
rs76763715 relates to more rapid progression of Hoehn and Yahr stage
See this image and copyright information in PMC

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