Dataset Information

Increased yield of full GBA sequencing in Ashkenazi Jews with Parkinson's disease.

ABSTRACT: BACKGROUND:Variants in GBA are the most common genetic risk factor for Parkinson's disease (PD), and are especially prevalent in the Ashkenazi Jewish (AJ) population. However, most studies on GBA in AJ genotype only seven selected Gaucher-associated pathogenic variants rather than sequencing the whole gene, which may leave carriers of PD-associated GBA variants undiscovered. METHODS:GBA was fully sequenced using molecular inversion probes (MIPs) and Sanger sequencing in 735 AJ PD patients and 662 AJ controls, from Israel and New York. Additional AJ control data (n?=?3044) from the Inflammatory Bowel Disease Exome Portal was used. RESULTS:Full GBA sequencing increased the number of variants discovered by 17.4%, compared to targeted genotyping. An additional 17 PD patients were identified with GBA-associated PD. The p.E326K variant was found in 1.6% of AJ PD patients, making it the second most common PD-associated GBA variant in AJ. GBA variants were found in 18% of PD patients and 7.5% of controls (OR?=?2.7, 95%CI?=?1.9-3.8, p?

SUBMITTER: Ruskey JA

PROVIDER: S-EPMC6261782 | biostudies-literature | 2019 Jan

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Increased yield of full GBA sequencing in Ashkenazi Jews with Parkinson's disease.

Ruskey Jennifer A JA Greenbaum Lior L Roncière Léanne L Alam Armaghan A Spiegelman Dan D Liong Christopher C Levy Oren A OA Waters Cheryl C Fahn Stanley S Marder Karen S KS Chung Wendy W Yahalom Gilad G Israeli-Korn Simon S Livneh Vered V Fay-Karmon Tsvia T Alcalay Roy N RN Hassin-Baer Sharon S Gan-Or Ziv Z

European journal of medical genetics 20180526 1

<h4>Background</h4>Variants in GBA are the most common genetic risk factor for Parkinson's disease (PD), and are especially prevalent in the Ashkenazi Jewish (AJ) population. However, most studies on GBA in AJ genotype only seven selected Gaucher-associated pathogenic variants rather than sequencing the whole gene, which may leave carriers of PD-associated GBA variants undiscovered.<h4>Methods</h4>GBA was fully sequenced using molecular inversion probes (MIPs) and Sanger sequencing in 735 AJ PD ...[more]

PMID: 29842932

Similar Datasets

Project description:Information on age-specific risk for Parkinson disease (PD) in patients with Gaucher disease (GD) and glucocerebrosidase (GBA) heterozygotes is important for understanding the pathophysiology of the genetic association and for counseling these populations.To estimate the age-specific risk for PD in Ashkenazi Jewish patients with type 1 GD and in GBA heterozygotes.The study included patients with GD from 2 tertiary centers, Shaare Zedek Medical Center, Jerusalem, Israel (n?=?332) and Mount Sinai School of Medicine, New York, New York (n?=?95). GBA noncarrier non-PD spouse control participants were recruited at the Center for Parkinson's Disease at Columbia University, New York (n?=?77). All participants were Ashekanzi Jewish and most patients (98.1%) with GD carried at least 1 N370S mutation.The main outcome measure was a diagnosis of PD. Diagnosis was established in patients with GD on examination. We used a validated family history interview that identifies PD with a sensitivity of 95.5% and specificity of 96.2% to identify PD in family members. Kaplan-Meier survival curves were used to estimate age-specific PD risk among patients with GD (n?=?427), among their parents who are obligate GBA mutation carriers (heterozygotes, n?=?694), and among noncarriers (parents of non-PD, non-GD control participants, n?=?154). The age-specific risk was compared among groups using the log-rank test.Among those who developed PD, patients with GD had a younger age at onset than GBA heterozygotes (mean, 54.2 vs 65.2 years, respectively; P?=?.003). Estimated age-specific risk for PD at 60 and 80 years of age was 4.7% and 9.1% among patients with GD, 1.5% and 7.7% among heterozygotes, and 0.7% and 2.1% among noncarriers, respectively. The risk for PD was higher in patients with GD than noncarriers (P?=?.008, log-rank test) and in heterozygotes than noncarriers (P?=?.03, log-rank test), but it did not reach statistical significance between patients with GD and GBA heterozygotes (P?=?.07, log-rank test).Patients with GD and GBA heterozygotes have an increased age-specific risk for PD compared with control individuals, with a similar magnitude of PD risk by 80 years of age; however, the number of mutant alleles may play an important role in age at PD onset.

Dataset Information

Increased yield of full GBA sequencing in Ashkenazi Jews with Parkinson's disease.

Publications

Increased yield of full GBA sequencing in Ashkenazi Jews with Parkinson's disease.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets