A common variant mapping to CACNA1A is associated with susceptibility to exfoliation syndrome
説明
Exfoliation syndrome (XFS) is the most common recognizable cause of open-angle glaucoma worldwide. To better understand the etiology of XFS, we conducted a genome-wide association study (GWAS) of 1,484 cases and 1,188 controls from Japan and followed up the most significant findings in a further 6,901 cases and 20,727 controls from 17 countries across 6 continents. We discovered a genome-wide significant association between a new locus (CACNA1A rs4926244) and increased susceptibility to XFS (odds ratio (OR) = 1.16, P = 3.36 × 10(-11)). Although we also confirmed overwhelming association at the LOXL1 locus, the key SNP marker (LOXL1 rs4886776) demonstrated allelic reversal depending on the ancestry group (Japanese: OR(A allele) = 9.87, P = 2.13 × 10(-217); non-Japanese: OR(A allele) = 0.49, P = 2.35 × 10(-31)). Our findings represent the first genetic locus outside of LOXL1 surpassing genome-wide significance for XFS and provide insight into the biology and pathogenesis of the disease.
収録刊行物
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- Nature Genetics
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Nature Genetics 47 (4), 387-392, 2015-02-23
Springer Science and Business Media LLC
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キーワード
- Medizin
- HeLa Cell
- Inbred C57BL
- Exfoliation Syndrome
- Mice
- MCF-7 Cell
- Animals; Asian Continental Ancestry Group; Calcium Channels; Case-Control Studies; Chromosome Mapping; Exfoliation Syndrome; Genetic Predisposition to Disease; Genome-Wide Association Study; Glaucoma, Open-Angle; HEK293 Cells; HeLa Cells; Humans; Japan; MCF-7 Cells; Mice; Mice, Inbred C57BL; Tumor Cells, Cultured; Polymorphism, Single Nucleotide; Genetics
- HEK293 Cell
- Japan
- HEK293 cells
- Open-angle
- Medicine and Health Sciences
- Tumor Cells, Cultured
- GWAS
- XFS
- MCF-7 cells
- Cultured
- Japanese population
- Life Sciences
- Chromosome Mapping
- Single Nucleotide
- Tumor Cells
- Open-Angle
- Pseudoexfoliation syndrome
- MCF-7 Cells
- Case-Control Studie
- Glaucoma, Open-Angle
- Human
- Asian Continental Ancestry Group
- Chromosome mapping
- 570
- 572
- Exfoliation syndrome
- open-angle glaucoma
- 610
- Case-control studies
- CACNA1A
- Tumor cells
- Calcium Channel
- Polymorphism, Single Nucleotide
- Sequence variants
- 1311 Genetics
- Asian People
- Genetics
- Animals
- Humans
- Genetic Predisposition to Disease
- HeLa cells
- Polymorphism
- Genome-wide association Study
- Animal
- Genetic predisposition to Disease
- Glaucoma
- Mice, Inbred C57BL
- Calcium channels
- HEK293 Cells
- Case-Control Studies
- Loxl1 gene polymorphisms
- Calcium Channels
- Genome-Wide Association Study
- HeLa Cells
詳細情報 詳細情報について
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- CRID
- 1360846641736593024
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- DOI
- 10.1038/ng.3226
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- ISSN
- 15461718
- 10614036
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- PubMed
- 26018902
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- 資料種別
- journal article
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- データソース種別
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- Crossref
- KAKEN
- OpenAIRE
