Increased yield of full GBA sequencing in Ashkenazi Jews with Parkinson's disease.
Journal
European journal of medical genetics
ISSN: 1878-0849
Titre abrégé: Eur J Med Genet
Pays: Netherlands
ID NLM: 101247089
Informations de publication
Date de publication:
Jan 2019
Jan 2019
Historique:
received:
19
02
2018
revised:
05
04
2018
accepted:
08
05
2018
pubmed:
31
5
2018
medline:
6
3
2019
entrez:
30
5
2018
Statut:
ppublish
Résumé
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. 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. 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 < 0.0001). Without full sequencing of GBA, or at minimum including p.E326K in the genotyping panel, a significant proportion of variant carriers go undiscovered and may be incorrectly assigned as non-carriers in studies or clinical trials.
Sections du résumé
BACKGROUND
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
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
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 < 0.0001).
CONCLUSION
CONCLUSIONS
Without full sequencing of GBA, or at minimum including p.E326K in the genotyping panel, a significant proportion of variant carriers go undiscovered and may be incorrectly assigned as non-carriers in studies or clinical trials.
Identifiants
pubmed: 29842932
pii: S1769-7212(18)30124-1
doi: 10.1016/j.ejmg.2018.05.005
pmc: PMC6261782
mid: NIHMS966203
pii:
doi:
Substances chimiques
Glucosylceramidase
EC 3.2.1.45
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
65-69Subventions
Organisme : NINDS NIH HHS
ID : K02 NS080915
Pays : United States
Organisme : NCRR NIH HHS
ID : UL1 RR024156
Pays : United States
Organisme : NCATS NIH HHS
ID : UL1 TR000040
Pays : United States
Informations de copyright
Copyright © 2018 Elsevier Masson SAS. All rights reserved.
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