A genome-wide association study suggests the HLA Class II region as the major susceptibility locus for IgA vasculitis
Abstract The genetic component of Immunoglobulin-A (IgA) vasculitis is still far to be elucidated. To increase the current knowledge on the genetic component of this vasculitis we performed the first genome-wide association study (GWAS) on this condition. 308 IgA vasculitis patients and 1,018 health...
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Nature Portfolio
2017-07-01
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| Series: | Scientific Reports |
| Online Access: | https://doi.org/10.1038/s41598-017-03915-2 |
| _version_ | 1818681529259261952 |
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| author | Raquel López-Mejías F. David Carmona Santos Castañeda Fernanda Genre Sara Remuzgo-Martínez Belén Sevilla-Perez Norberto Ortego-Centeno Javier Llorca Begoña Ubilla Verónica Mijares Trinitario Pina José A. Miranda-Filloy Antonio Navas Parejo Diego de Argila Maximiliano Aragües Esteban Rubio Manuel León Luque Juan María Blanco-Madrigal Eva Galíndez-Aguirregoikoa David Jayne Ricardo Blanco Javier Martín Miguel A. González-Gay |
| author_facet | Raquel López-Mejías F. David Carmona Santos Castañeda Fernanda Genre Sara Remuzgo-Martínez Belén Sevilla-Perez Norberto Ortego-Centeno Javier Llorca Begoña Ubilla Verónica Mijares Trinitario Pina José A. Miranda-Filloy Antonio Navas Parejo Diego de Argila Maximiliano Aragües Esteban Rubio Manuel León Luque Juan María Blanco-Madrigal Eva Galíndez-Aguirregoikoa David Jayne Ricardo Blanco Javier Martín Miguel A. González-Gay |
| author_sort | Raquel López-Mejías |
| collection | DOAJ |
| description | Abstract The genetic component of Immunoglobulin-A (IgA) vasculitis is still far to be elucidated. To increase the current knowledge on the genetic component of this vasculitis we performed the first genome-wide association study (GWAS) on this condition. 308 IgA vasculitis patients and 1,018 healthy controls from Spain were genotyped by Illumina HumanCore BeadChips. Imputation of GWAS data was performed using the 1000 Genomes Project Phase III dataset as reference panel. After quality control filters and GWAS imputation, 285 patients and 1,006 controls remained in the datasets and were included in further analysis. Additionally, the human leukocyte antigen (HLA) region was comprehensively studied by imputing classical alleles and polymorphic amino acid positions. A linkage disequilibrium block of polymorphisms located in the HLA class II region surpassed the genome-wide level of significance (OR = 0.56, 95% CI = 0.46–0.68). Although no polymorphic amino acid positions were associated at the genome-wide level of significance, P-values of potential relevance were observed for the positions 13 and 11 of HLA-DRB1 (P = 6.67E-05, P = 1.88E-05, respectively). Outside the HLA, potential associations were detected, but none of them were close to the statistical significance. In conclusion, our study suggests that IgA vasculitis is an archetypal HLA class II disease. |
| first_indexed | 2024-12-17T10:04:24Z |
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| id | doaj.art-3e33d0a736e14f4593fe38919470b3d3 |
| institution | Directory Open Access Journal |
| issn | 2045-2322 |
| language | English |
| last_indexed | 2024-12-17T10:04:24Z |
| publishDate | 2017-07-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj.art-3e33d0a736e14f4593fe38919470b3d32022-12-21T21:53:11ZengNature PortfolioScientific Reports2045-23222017-07-01711610.1038/s41598-017-03915-2A genome-wide association study suggests the HLA Class II region as the major susceptibility locus for IgA vasculitisRaquel López-Mejías0F. David Carmona1Santos Castañeda2Fernanda Genre3Sara Remuzgo-Martínez4Belén Sevilla-Perez5Norberto Ortego-Centeno6Javier Llorca7Begoña Ubilla8Verónica Mijares9Trinitario Pina10José A. Miranda-Filloy11Antonio Navas Parejo12Diego de Argila13Maximiliano Aragües14Esteban Rubio15Manuel León Luque16Juan María Blanco-Madrigal17Eva Galíndez-Aguirregoikoa18David Jayne19Ricardo Blanco20Javier Martín21Miguel A. González-Gay22Epidemiology, Genetics and Atherosclerosis Research Group on Systemic Inflammatory Diseases, Rheumatology Division, Hospital Universitario Marqués de Valdecilla, IDIVALInstituto de Parasitología y Biomedicina ‘López-Neyra’, CSIC, PTS GranadaRheumatology Department, Hospital Universitario La Princesa, IIS-IPrincesaEpidemiology, Genetics and Atherosclerosis Research Group on Systemic Inflammatory Diseases, Rheumatology Division, Hospital Universitario Marqués de Valdecilla, IDIVALEpidemiology, Genetics and Atherosclerosis Research Group on Systemic Inflammatory Diseases, Rheumatology Division, Hospital Universitario Marqués de Valdecilla, IDIVALMedicine Department, Hospital Universitario San CecilioMedicine Department, Hospital Universitario San CecilioEpidemiology and Computational Biology Department, School of Medicine, University of Cantabria, and CIBER Epidemiología y Salud Pública (CIBERESP), IDIVALEpidemiology, Genetics and Atherosclerosis Research Group on Systemic Inflammatory Diseases, Rheumatology Division, Hospital Universitario Marqués de Valdecilla, IDIVALEpidemiology, Genetics and Atherosclerosis Research Group on Systemic Inflammatory Diseases, Rheumatology Division, Hospital Universitario Marqués de Valdecilla, IDIVALEpidemiology, Genetics and Atherosclerosis Research Group on Systemic Inflammatory Diseases, Rheumatology Division, Hospital Universitario Marqués de Valdecilla, IDIVALDivision of Rheumatology, Hospital Universitario Lucus AugustiNephrology Department, Hospital Universitario San CecilioDermatology Department, Hospital Universitario La Princesa, IIS-IPrincesaDermatology Department, Hospital Universitario La Princesa, IIS-IPrincesaRheumatology Department, Hospital Universitario Virgen del RocíoRheumatology Department, Hospital Universitario Virgen del RocíoRheumatology Department, Hospital Universitario de BasurtoRheumatology Department, Hospital Universitario de BasurtoDepartment of Medicine, University of CambridgeEpidemiology, Genetics and Atherosclerosis Research Group on Systemic Inflammatory Diseases, Rheumatology Division, Hospital Universitario Marqués de Valdecilla, IDIVALInstituto de Parasitología y Biomedicina ‘López-Neyra’, CSIC, PTS GranadaEpidemiology, Genetics and Atherosclerosis Research Group on Systemic Inflammatory Diseases, Rheumatology Division, Hospital Universitario Marqués de Valdecilla, IDIVALAbstract The genetic component of Immunoglobulin-A (IgA) vasculitis is still far to be elucidated. To increase the current knowledge on the genetic component of this vasculitis we performed the first genome-wide association study (GWAS) on this condition. 308 IgA vasculitis patients and 1,018 healthy controls from Spain were genotyped by Illumina HumanCore BeadChips. Imputation of GWAS data was performed using the 1000 Genomes Project Phase III dataset as reference panel. After quality control filters and GWAS imputation, 285 patients and 1,006 controls remained in the datasets and were included in further analysis. Additionally, the human leukocyte antigen (HLA) region was comprehensively studied by imputing classical alleles and polymorphic amino acid positions. A linkage disequilibrium block of polymorphisms located in the HLA class II region surpassed the genome-wide level of significance (OR = 0.56, 95% CI = 0.46–0.68). Although no polymorphic amino acid positions were associated at the genome-wide level of significance, P-values of potential relevance were observed for the positions 13 and 11 of HLA-DRB1 (P = 6.67E-05, P = 1.88E-05, respectively). Outside the HLA, potential associations were detected, but none of them were close to the statistical significance. In conclusion, our study suggests that IgA vasculitis is an archetypal HLA class II disease.https://doi.org/10.1038/s41598-017-03915-2 |
| spellingShingle | Raquel López-Mejías F. David Carmona Santos Castañeda Fernanda Genre Sara Remuzgo-Martínez Belén Sevilla-Perez Norberto Ortego-Centeno Javier Llorca Begoña Ubilla Verónica Mijares Trinitario Pina José A. Miranda-Filloy Antonio Navas Parejo Diego de Argila Maximiliano Aragües Esteban Rubio Manuel León Luque Juan María Blanco-Madrigal Eva Galíndez-Aguirregoikoa David Jayne Ricardo Blanco Javier Martín Miguel A. González-Gay A genome-wide association study suggests the HLA Class II region as the major susceptibility locus for IgA vasculitis Scientific Reports |
| title | A genome-wide association study suggests the HLA Class II region as the major susceptibility locus for IgA vasculitis |
| title_full | A genome-wide association study suggests the HLA Class II region as the major susceptibility locus for IgA vasculitis |
| title_fullStr | A genome-wide association study suggests the HLA Class II region as the major susceptibility locus for IgA vasculitis |
| title_full_unstemmed | A genome-wide association study suggests the HLA Class II region as the major susceptibility locus for IgA vasculitis |
| title_short | A genome-wide association study suggests the HLA Class II region as the major susceptibility locus for IgA vasculitis |
| title_sort | genome wide association study suggests the hla class ii region as the major susceptibility locus for iga vasculitis |
| url | https://doi.org/10.1038/s41598-017-03915-2 |
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