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Exonic Re-Sequencing of the Chromosome 2q24.3 Parkinson’s Disease Locus

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...

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Autores principales: 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.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4474914/
https://www.ncbi.nlm.nih.gov/pubmed/26090850
http://dx.doi.org/10.1371/journal.pone.0128586
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author 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.
author_facet 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.
author_sort Labbé, Catherine
collection PubMed
description 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.
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spelling pubmed-44749142015-06-30 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. PLoS One Research Article 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. Public Library of Science 2015-06-19 /pmc/articles/PMC4474914/ /pubmed/26090850 http://dx.doi.org/10.1371/journal.pone.0128586 Text en © 2015 Labbé et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
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
title Exonic Re-Sequencing of the Chromosome 2q24.3 Parkinson’s Disease Locus
title_full Exonic Re-Sequencing of the Chromosome 2q24.3 Parkinson’s Disease Locus
title_fullStr Exonic Re-Sequencing of the Chromosome 2q24.3 Parkinson’s Disease Locus
title_full_unstemmed Exonic Re-Sequencing of the Chromosome 2q24.3 Parkinson’s Disease Locus
title_short Exonic Re-Sequencing of the Chromosome 2q24.3 Parkinson’s Disease Locus
title_sort exonic re-sequencing of the chromosome 2q24.3 parkinson’s disease locus
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4474914/
https://www.ncbi.nlm.nih.gov/pubmed/26090850
http://dx.doi.org/10.1371/journal.pone.0128586
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