Journal of Neurology

, Volume 262, Issue 11, pp 2443–2447

The Alzheimer disease BIN1 locus as a modifier of GBA-associated Parkinson disease

  • Z. Gan-Or
  • I. Amshalom
  • A. Bar-Shira
  • M. Gana-Weisz
  • A. Mirelman
  • K. Marder
  • S. Bressman
  • N. Giladi
  • A. Orr-Urtreger
Original Communication

DOI: 10.1007/s00415-015-7868-3

Cite this article as:
Gan-Or, Z., Amshalom, I., Bar-Shira, A. et al. J Neurol (2015) 262: 2443. doi:10.1007/s00415-015-7868-3

Abstract

GBA mutations are among the most common genetic risk factors for Parkinson disease (PD) worldwide. We aimed to identify genetic modifiers of the age at onset (AAO) in GBA-associated PD. The study included a genome-wide discovery phase, including a cohort of 79 patients with the GBA p.N370S mutation, and candidate validation and replication analyses of 8 SNPs in patients with mild (n = 113) and severe (n = 41) GBA mutations. Genotyping was performed using the Affymetrix human SNP 6.0 array and TaqMan assays. In the genome-wide phase, none of the SNPs passed the genome-wide significance threshold. Eight SNPs were selected for further analysis from the top hits. In all GBA-associated PD patients (n = 153), the BIN1 rs13403026 minor allele was associated with an older AAO (12.4 ± 5.9 years later, p = 0.0001), compared to patients homozygous for the major allele. Furthermore, the AAO was 10.7 ± 6.8 years later in patients with mild GBA mutations, (p = 0.005, validation group), and 17.1 ± 2.5 years later in patients with severe GBA mutations (p = 0.01, replication). Our results suggest that alterations in the BIN1 locus, previously associated with Alzheimer disease, may modify the AAO of GBA-associated PD. More studies in other populations are required to examine the role of BIN1-related variants in GBA-associated PD.

Keywords

BIN1 GBA Genetics Parkinson disease 

Supplementary material

415_2015_7868_MOESM1_ESM.docx (39 kb)
Supplementary material 1 (DOCX 38 kb)

Copyright information

© Springer-Verlag Berlin Heidelberg 2015

Authors and Affiliations

  • Z. Gan-Or
    • 1
    • 3
  • I. Amshalom
    • 1
    • 3
  • A. Bar-Shira
    • 1
  • M. Gana-Weisz
    • 1
  • A. Mirelman
    • 2
  • K. Marder
    • 4
  • S. Bressman
    • 5
  • N. Giladi
    • 2
    • 3
  • A. Orr-Urtreger
    • 1
    • 3
  1. 1.The Genetic InstituteTel Aviv Sourasky Medical CenterTel AvivIsrael
  2. 2.Movement Disorders Unit, Department of Neurology, Parkinson CenterTel Aviv Sourasky Medical CenterTel AvivIsrael
  3. 3.The Sackler Faculty of MedicineTel-Aviv UniversityTel AvivIsrael
  4. 4.Department of Neurology, Columbia Presbyterian Medical CenterColumbia UniversityNew YorkUSA
  5. 5.Department of NeurologyBeth Israel Medical CenterNew YorkUSA