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, Joanne Wojcieszek, R. F. Pfeiffer, Tatiana Foroud

Research output: Contribution to journalArticle

120 Citations (Scopus)

Abstract

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
Pages (from-to)310-316
Number of pages7
JournalNeurology
Volume72
Issue number4
DOIs
StatePublished - Jan 27 2009

Fingerprint

Glucosylceramidase
Disease Susceptibility
Age of Onset
Parkinson Disease
Mutation
Lod Score
Genes
Exons

ASJC Scopus subject areas

  • Clinical Neurology

Cite this

Nichols, W. C., Pankratz, N., Marek, D. K., Pauciulo, M. W., Elsaesser, V. E., Halter, C. A., ... Foroud, T. (2009). Mutations in GBA are associated with familial Parkinson disease susceptibility and age at onset. Neurology, 72(4), 310-316. https://doi.org/10.1212/01.wnl.0000327823.81237.d1

Mutations in GBA are associated with familial Parkinson disease susceptibility and age at onset. / Nichols, W. C.; Pankratz, N.; Marek, D. K.; Pauciulo, M. W.; Elsaesser, V. E.; Halter, C. A.; Rudolph, A.; Wojcieszek, Joanne; Pfeiffer, R. F.; Foroud, Tatiana.

In: Neurology, Vol. 72, No. 4, 27.01.2009, p. 310-316.

Research output: Contribution to journalArticle

Nichols, WC, Pankratz, N, Marek, DK, Pauciulo, MW, Elsaesser, VE, Halter, CA, Rudolph, A, Wojcieszek, J, Pfeiffer, RF & Foroud, T 2009, 'Mutations in GBA are associated with familial Parkinson disease susceptibility and age at onset', Neurology, vol. 72, no. 4, pp. 310-316. https://doi.org/10.1212/01.wnl.0000327823.81237.d1
Nichols WC, Pankratz N, Marek DK, Pauciulo MW, Elsaesser VE, Halter CA et al. Mutations in GBA are associated with familial Parkinson disease susceptibility and age at onset. Neurology. 2009 Jan 27;72(4):310-316. https://doi.org/10.1212/01.wnl.0000327823.81237.d1
Nichols, W. C. ; Pankratz, N. ; Marek, D. K. ; Pauciulo, M. W. ; Elsaesser, V. E. ; Halter, C. A. ; Rudolph, A. ; Wojcieszek, Joanne ; Pfeiffer, R. F. ; Foroud, Tatiana. / Mutations in GBA are associated with familial Parkinson disease susceptibility and age at onset. In: Neurology. 2009 ; Vol. 72, No. 4. pp. 310-316.
@article{ca2b1fb102914d9aaca7372d1bf2863e,
title = "Mutations in GBA are associated with familial Parkinson disease susceptibility and age at onset",
abstract = "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.",
author = "Nichols, {W. C.} and N. Pankratz and Marek, {D. K.} and Pauciulo, {M. W.} and Elsaesser, {V. E.} and Halter, {C. A.} and A. Rudolph and Joanne Wojcieszek and Pfeiffer, {R. F.} and Tatiana Foroud",
year = "2009",
month = "1",
day = "27",
doi = "10.1212/01.wnl.0000327823.81237.d1",
language = "English",
volume = "72",
pages = "310--316",
journal = "Neurology",
issn = "0028-3878",
publisher = "Lippincott Williams and Wilkins",
number = "4",

}

TY - JOUR

T1 - Mutations in GBA are associated with familial Parkinson disease susceptibility and age at onset

AU - Nichols, W. C.

AU - Pankratz, N.

AU - Marek, D. K.

AU - Pauciulo, M. W.

AU - Elsaesser, V. E.

AU - Halter, C. A.

AU - Rudolph, A.

AU - Wojcieszek, Joanne

AU - Pfeiffer, R. F.

AU - Foroud, Tatiana

PY - 2009/1/27

Y1 - 2009/1/27

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=60549098601&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=60549098601&partnerID=8YFLogxK

U2 - 10.1212/01.wnl.0000327823.81237.d1

DO - 10.1212/01.wnl.0000327823.81237.d1

M3 - Article

C2 - 18987351

AN - SCOPUS:60549098601

VL - 72

SP - 310

EP - 316

JO - Neurology

JF - Neurology

SN - 0028-3878

IS - 4

ER -