@article{03f6b6018ad34e03a6cf0a5d2b7c51fd,
title = "Variants in GBA, SNCA, and MAPT influence Parkinson disease risk, age at onset, and progression",
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",
author = "Davis, {Albert A.} and Andruska, {Kristin M.} and Benitez, {Bruno A.} and Racette, {Brad A.} and Perlmutter, {Joel S.} and Carlos Cruchaga",
note = "Funding Information: The authors thank Susan Loftin and Karen Klumpp for their expert technical assistance. This work was supported by grants from NINDS ( NS075321 , NS41509 , NS058714 , and R01AG044546 ); the Barnes Jewish Hospital Foundation (BJHF); the American Parkinson Disease Association (APDA) Advanced Research Center for Parkinson Disease at Washington University in St. Louis; the Greater St. Louis Chapter of the APDA ; the Barnes Jewish Hospital Foundation (Elliot Stein Family Fund and Parkinson Disease Research Fund); the Michael J. Fox Foundation for Parkinson's Research ; Alzheimer's Association ; and Weston Brain Institute . This research was conducted while Carlos Cruchaga was a recipient of a New Investigator Award in Alzheimer's disease from the American Federation for Aging Research. Carlos Cruchaga is a recipient of a BrightFocus Foundation Alzheimer's Disease Research Grant ( A2013359S ). Data used in the preparation of this article were obtained from the Parkinson's Progression Markers Initiative (PPMI) database ( www.ppmi-info.org/data ). For up-to-date information on the study, visit www.ppmi-info.org . PPMI—a public-private partnership—is funded by the Michael J. Fox Foundation for Parkinson's Research and funding partners, including Abbvie , Avid Radiopharmaceuticals , Biogen Idec , Bristol-Myers Squibb , Covance , GE Healthcare , Genentech , GlaxoSmithKline , Lilly , Lundbeck , Merck , Meso Scale Discovery , Pfizer , Piramal , Roche , and UCB . Publisher Copyright: {\textcopyright} 2016 Elsevier Inc.",
year = "2016",
month = jan,
day = "1",
doi = "10.1016/j.neurobiolaging.2015.09.014",
language = "English",
volume = "37",
pages = "209.e1--209.e7",
journal = "Neurobiology of Aging",
issn = "0197-4580",
}