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. 2016 Jan;31(1):79-85.
doi: 10.1002/mds.26374. Epub 2015 Aug 13.

Baseline genetic associations in the Parkinson's Progression Markers Initiative (PPMI)

Mike A Nalls  1 , Margaux F Keller  2 , Dena G Hernandez  1 , Lan Chen  2 , David J Stone  2 , Andrew B Singleton  1 ; Parkinson's Progression Marker Initiative (PPMI) investigators
Collaborators, Affiliations

Baseline genetic associations in the Parkinson's Progression Markers Initiative (PPMI)

Mike A Nalls et al. Mov Disord. 2016 Jan.

Abstract

Background: The Parkinson's Progression Marker Initiative is an international multicenter study whose main goal is investigating markers for Parkinson's disease (PD) progression as part of a path to a treatment for the disease. This manuscript describes the baseline genetic architecture of this study, providing not only a catalog of disease-linked variants and mutations, but also quantitative measures with which to adjust for population structure.

Methods: Three hundred eighty-three newly diagnosed typical PD cases, 65 atypical PD and 178 healthy controls, from the Parkinson's Progression Marker Initiative study have been genotyped on the NeuroX or Immunochip arrays. These data are freely available to all researchers interested in pursuing PD research within the Parkinson's Progression Marker Initiative.

Results: The Parkinson's Progression Marker Initiative represents a study population with low genetic heterogeneity. We recapitulate known PD associations from large-scale genome-wide association studies and refine genetic risk score models for PD predictability (area under the curve, ∼0.74). We show the presence of six LRRK2 p.G2019S and nine GBA p.N370S mutation carriers.

Conclusions: The Parkinson's Progression Marker Initiative study and its genetic data are useful in studies of PD biomarkers. The genetic architecture described here will be useful in the analysis of myriad biological and clinical traits within this study.

Keywords: GWAS; Parkinson's disease; genetic risk score; genetics.

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Figures

Figure 1
Figure 1. Population substructure within the PPMI genetics dataset
Abbreviations for HapMap Phase 3 reference populations as follows: ASW: African ancestry in Southwest USA; CEU: Utah residents with Northern and Western European ancestry from the CEPH collection; CHB: Han Chinese in Beijing, China; CHD: Chinese in Metropolitan Denver, Colorado; GIH: Gujarati Indians in Houston, Texas; JPT: Japanese in Tokyo, Japan; LWK: Luhya in Webuye, Kenya; MEX: Mexican ancestry in Los Angeles, California; MKK: Maasai in Kinyawa, Kenya; TSI: Toscani in Italia; YRI: Yoruba in Ibadan, Nigeria.
Figure 2
Figure 2. Comparison of PPMI and large-scale cross-sectional meta-analysis results
Panel A, areas under the curve from receiver operator curve analyses of crGRS; Panel B, comparison of odds ratios by quintile of genetic risk. The data for cross sectional analysis was taken from our previously published work (7).
Figure 2
Figure 2. Comparison of PPMI and large-scale cross-sectional meta-analysis results
Panel A, areas under the curve from receiver operator curve analyses of crGRS; Panel B, comparison of odds ratios by quintile of genetic risk. The data for cross sectional analysis was taken from our previously published work (7).
See this image and copyright information in PMC

References

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