Exonic re-sequencing of the chromosome 2q24.3 Parkinson's disease locus

Catherine Labbé, Kotaro Ogaki, Oswaldo Lorenzo-Betancor, Minerva M Carrasquillo, Michael G. Heckman, Allan McCarthy, Alexandra I. Soto-Ortolaza, Ronald L. Walton, Timothy Lynch, Joanna Siuda, Grzegorz Opala, Anna Krygowska-Wajs, Maria Barcikowska, Krzysztof Czyzewski, Dennis W Dickson, Ryan J. Uitti, Zbigniew K Wszolek, Owen A Ross

Research output: Contribution to journalArticle

Abstract

Genome-wide association studies (GWAS) in Parkinson's disease (PD) have identified over 20 genomic regions associated with disease risk. Many of these loci include several candidate genes making it difficult to pinpoint the causal gene. The locus on chromosome 2q24.3 encompasses three genes: B3GALT1, STK39, and CERS6. In order to identify if the causal variants are simple missense changes, we sequenced all 31 exons of these three genes in 187 patients with PD. We identified 13 exonic variants including four non-synonymous and three insertion/deletion variants (indels). These non-synonymous variants and rs2102808, the GWAS tag SNP, were genotyped in three independent series consisting of a total of 1976 patients and 1596 controls. Our results show that the seven identified 2q24.3 coding variants are not independently responsible for the GWAS association signal at the locus; however, there is a haplotype, which contains both rs2102808 and a STK39 exon 1 6bp indel variant, that is significantly associated with PD risk (Odds Ratio [OR] = 1.35, 95% CI: 1.11-1.64, P = 0.003). This haplotype is more associated than each of the two variants independently (OR = 1.23, P = 0.005 and 1.10, P = 0.10, respectively). Our findings suggest that the risk variant is likely located in a non-coding region. Additional sequencing of the locus including promoter and regulatory regions will be needed to pinpoint the association at this locus that leads to an increased risk to PD.

Original languageEnglish (US)
Article numbere0128586
JournalPLoS One
Volume10
Issue number6
DOIs
StatePublished - Jun 19 2015

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Parkinson disease
Chromosomes
Parkinson Disease
Genome-Wide Association Study
Genes
chromosomes
loci
Odds Ratio
Haplotypes
Exons
odds ratio
exons
haplotypes
genes
Nucleic Acid Regulatory Sequences
Genetic Promoter Regions
Single Nucleotide Polymorphism
promoter regions
genomics
genome-wide association study

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Exonic re-sequencing of the chromosome 2q24.3 Parkinson's disease locus. / Labbé, Catherine; Ogaki, Kotaro; Lorenzo-Betancor, Oswaldo; Carrasquillo, Minerva M; Heckman, Michael G.; McCarthy, Allan; Soto-Ortolaza, Alexandra I.; Walton, Ronald L.; Lynch, Timothy; Siuda, Joanna; Opala, Grzegorz; Krygowska-Wajs, Anna; Barcikowska, Maria; Czyzewski, Krzysztof; Dickson, Dennis W; Uitti, Ryan J.; Wszolek, Zbigniew K; Ross, Owen A.

In: PLoS One, Vol. 10, No. 6, e0128586, 19.06.2015.

Research output: Contribution to journalArticle

Labbé, C, Ogaki, K, Lorenzo-Betancor, O, Carrasquillo, MM, Heckman, MG, McCarthy, A, Soto-Ortolaza, AI, Walton, RL, Lynch, T, Siuda, J, Opala, G, Krygowska-Wajs, A, Barcikowska, M, Czyzewski, K, Dickson, DW, Uitti, RJ, Wszolek, ZK & Ross, OA 2015, 'Exonic re-sequencing of the chromosome 2q24.3 Parkinson's disease locus', PLoS One, vol. 10, no. 6, e0128586. https://doi.org/10.1371/journal.pone.0128586
Labbé C, Ogaki K, Lorenzo-Betancor O, Carrasquillo MM, Heckman MG, McCarthy A et al. Exonic re-sequencing of the chromosome 2q24.3 Parkinson's disease locus. PLoS One. 2015 Jun 19;10(6). e0128586. https://doi.org/10.1371/journal.pone.0128586
Labbé, Catherine ; Ogaki, Kotaro ; Lorenzo-Betancor, Oswaldo ; Carrasquillo, Minerva M ; Heckman, Michael G. ; McCarthy, Allan ; Soto-Ortolaza, Alexandra I. ; Walton, Ronald L. ; Lynch, Timothy ; Siuda, Joanna ; Opala, Grzegorz ; Krygowska-Wajs, Anna ; Barcikowska, Maria ; Czyzewski, Krzysztof ; Dickson, Dennis W ; Uitti, Ryan J. ; Wszolek, Zbigniew K ; Ross, Owen A. / Exonic re-sequencing of the chromosome 2q24.3 Parkinson's disease locus. In: PLoS One. 2015 ; Vol. 10, No. 6.
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AU - Ogaki, Kotaro

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AU - Heckman, Michael G.

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AU - Soto-Ortolaza, Alexandra I.

AU - Walton, Ronald L.

AU - Lynch, Timothy

AU - Siuda, Joanna

AU - Opala, Grzegorz

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AU - Barcikowska, Maria

AU - Czyzewski, Krzysztof

AU - Dickson, Dennis W

AU - Uitti, Ryan J.

AU - Wszolek, Zbigniew K

AU - Ross, Owen A

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