Association between a common immunoglobulin heavy chain allele and rheumatic heart disease risk in Oceania.
The indigenous populations of the South Pacific experience a high burden of rheumatic heart disease (RHD). Here we report a genome-wide association study (GWAS) of RHD susceptibility in 2,852 individuals recruited in eight Oceanian countries. Stratifying by ancestry, we analysed genotyped and impute...
| Main Authors: | , , , , , , , , , , , , , , , , , , |
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| Format: | Journal article |
| Language: | English |
| Published: |
Nature Publishing Group
2017
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| _version_ | 1797060365369999360 |
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| author | Parks, T Mirabel, M Kado, J Auckland, K Nowak, J Rautanen, A Mentzer, A Marijon, E Jouven, X Perman, M Cua, T Kauwe, J Allen, J Taylor, H Robson, K Deane, C Steer, A Hill, A Pacific Islands Rheumatic Heart Disease Genetics Network |
| author_facet | Parks, T Mirabel, M Kado, J Auckland, K Nowak, J Rautanen, A Mentzer, A Marijon, E Jouven, X Perman, M Cua, T Kauwe, J Allen, J Taylor, H Robson, K Deane, C Steer, A Hill, A Pacific Islands Rheumatic Heart Disease Genetics Network |
| author_sort | Parks, T |
| collection | OXFORD |
| description | The indigenous populations of the South Pacific experience a high burden of rheumatic heart disease (RHD). Here we report a genome-wide association study (GWAS) of RHD susceptibility in 2,852 individuals recruited in eight Oceanian countries. Stratifying by ancestry, we analysed genotyped and imputed variants in Melanesians (607 cases and 1,229 controls) before follow-up of suggestive loci in three further ancestral groups: Polynesians, South Asians and Mixed or other populations (totalling 399 cases and 617 controls). We identify a novel susceptibility signal in the immunoglobulin heavy chain (IGH) locus centring on a haplotype of nonsynonymous variants in the IGHV4-61 gene segment corresponding to the IGHV4-61*02 allele. We show each copy of IGHV4-61*02 is associated with a 1.4-fold increase in the risk of RHD (odds ratio 1.43, 95% confidence intervals 1.27-1.61, P=4.1 × 10(-9)). These findings provide new insight into the role of germline variation in the IGH locus in disease susceptibility. |
| first_indexed | 2024-03-06T20:16:05Z |
| format | Journal article |
| id | oxford-uuid:2c2dc82b-53d2-4f92-a844-48f20d0b34ff |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-06T20:16:05Z |
| publishDate | 2017 |
| publisher | Nature Publishing Group |
| record_format | dspace |
| spelling | oxford-uuid:2c2dc82b-53d2-4f92-a844-48f20d0b34ff2022-03-26T12:35:33ZAssociation between a common immunoglobulin heavy chain allele and rheumatic heart disease risk in Oceania.Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:2c2dc82b-53d2-4f92-a844-48f20d0b34ffEnglishSymplectic Elements at OxfordNature Publishing Group2017Parks, TMirabel, MKado, JAuckland, KNowak, JRautanen, AMentzer, AMarijon, EJouven, XPerman, MCua, TKauwe, JAllen, JTaylor, HRobson, KDeane, CSteer, AHill, APacific Islands Rheumatic Heart Disease Genetics NetworkThe indigenous populations of the South Pacific experience a high burden of rheumatic heart disease (RHD). Here we report a genome-wide association study (GWAS) of RHD susceptibility in 2,852 individuals recruited in eight Oceanian countries. Stratifying by ancestry, we analysed genotyped and imputed variants in Melanesians (607 cases and 1,229 controls) before follow-up of suggestive loci in three further ancestral groups: Polynesians, South Asians and Mixed or other populations (totalling 399 cases and 617 controls). We identify a novel susceptibility signal in the immunoglobulin heavy chain (IGH) locus centring on a haplotype of nonsynonymous variants in the IGHV4-61 gene segment corresponding to the IGHV4-61*02 allele. We show each copy of IGHV4-61*02 is associated with a 1.4-fold increase in the risk of RHD (odds ratio 1.43, 95% confidence intervals 1.27-1.61, P=4.1 × 10(-9)). These findings provide new insight into the role of germline variation in the IGH locus in disease susceptibility. |
| spellingShingle | Parks, T Mirabel, M Kado, J Auckland, K Nowak, J Rautanen, A Mentzer, A Marijon, E Jouven, X Perman, M Cua, T Kauwe, J Allen, J Taylor, H Robson, K Deane, C Steer, A Hill, A Pacific Islands Rheumatic Heart Disease Genetics Network Association between a common immunoglobulin heavy chain allele and rheumatic heart disease risk in Oceania. |
| title | Association between a common immunoglobulin heavy chain allele and rheumatic heart disease risk in Oceania. |
| title_full | Association between a common immunoglobulin heavy chain allele and rheumatic heart disease risk in Oceania. |
| title_fullStr | Association between a common immunoglobulin heavy chain allele and rheumatic heart disease risk in Oceania. |
| title_full_unstemmed | Association between a common immunoglobulin heavy chain allele and rheumatic heart disease risk in Oceania. |
| title_short | Association between a common immunoglobulin heavy chain allele and rheumatic heart disease risk in Oceania. |
| title_sort | association between a common immunoglobulin heavy chain allele and rheumatic heart disease risk in oceania |
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