Mutations in GBA are associated with familial Parkinson disease susceptibility and age at onset

W. C. Nichols, N. Pankratz, D. K. Marek, M. W. Pauciulo, V. E. Elsaesser, C. A. Halter, A. Rudolph, J. Wojcieszek, R. F. Pfeiffer, T. Foroud

Research output: Contribution to journalArticlepeer-review

175 Scopus citations


OBJECTIVE: To characterize sequence variation within the glucocerebrosidase (GBA) gene in a select subset of our sample of patients with familial Parkinson disease (PD) and then to test in our full sample whether these sequence variants increased the risk for PD and were associated with an earlier onset of disease. METHODS: We performed a comprehensive study of all GBA exons in one patient with PD from each of 96 PD families, selected based on the family-specific lod scores at the GBA locus. Identified GBA variants were subsequently screened in all 1325 PD cases from 566 multiplex PD families and in 359 controls. RESULTS: Nine different GBA variants, five previously reported, were identified in 21 of the 96 PD cases sequenced. Screening for these variants in the full sample identified 161 variant carriers (12.2%) in 99 different PD families. An unbiased estimate of the frequency of the five previously reported GBA variants in the familial PD sample was 12.6% and in the control sample was 5.3% (odds ratio 2.6; 95% confidence interval 1.5-4.4). Presence of a GBA variant was associated with an earlier age at onset (p = 0.0001). On average, those patients carrying a GBA variant had onset with PD 6.04 years earlier than those without a GBA variant. CONCLUSIONS: This study suggests that GBA is a susceptibility gene for familial Parkinson disease (PD) and patients with GBA variants have an earlier age at onset than patients with PD without GBA variants.

Original languageEnglish (US)
Pages (from-to)310-316
Number of pages7
Issue number4
StatePublished - Jan 27 2009

Bibliographical note

Funding Information:
Supported by R01 NS37167, MO1 RR-00750, and the National Cell Repository for Alzheimer's Disease (U24 AG021886). This study used samples and clinical data from the National Institute of Neurological Disorders and Stroke Human Genetics Resource Center DNA and Cell Line Repository ( ).


Dive into the research topics of 'Mutations in GBA are associated with familial Parkinson disease susceptibility and age at onset'. Together they form a unique fingerprint.

Cite this