Association between a common immunoglobulin heavy chain allele and rheumatic heart disease risk in Oceania.
Identifieur interne : 000B96 ( PubMed/Curation ); précédent : 000B95; suivant : 000B97Association between a common immunoglobulin heavy chain allele and rheumatic heart disease risk in Oceania.
Auteurs : Tom Parks [Royaume-Uni] ; Mariana M. Mirabel [France] ; Joseph Kado [Fidji] ; Kathryn Auckland [Royaume-Uni] ; Jaroslaw Nowak [Royaume-Uni] ; Anna Rautanen [Royaume-Uni] ; Alexander J. Mentzer [Royaume-Uni] ; Eloi Marijon [France] ; Xavier Jouven [France] ; Mai Ling Perman [Fidji] ; Tuliana Cua [Fidji] ; John K. Kauwe [États-Unis] ; John B. Allen [États-Unis] ; Henry Taylor [Samoa] ; Kathryn J. Robson [Royaume-Uni] ; Charlotte M. Deane [Royaume-Uni] ; Andrew C. Steer [Australie] ; Adrian V S. Hill [Royaume-Uni]Source :
- Nature communications [ 2041-1723 ] ; 2017.
Abstract
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.
DOI: 10.1038/ncomms14946
PubMed: 28492228
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<author><name sortKey="Allen, John B" sort="Allen, John B" uniqKey="Allen J" first="John B" last="Allen">John B. Allen</name>
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<author><name sortKey="Taylor, Henry" sort="Taylor, Henry" uniqKey="Taylor H" first="Henry" last="Taylor">Henry Taylor</name>
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<author><name sortKey="Deane, Charlotte M" sort="Deane, Charlotte M" uniqKey="Deane C" first="Charlotte M" last="Deane">Charlotte M. Deane</name>
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<front><div type="abstract" xml:lang="en">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.</div>
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<ELocationID EIdType="doi" ValidYN="Y">10.1038/ncomms14946</ELocationID>
<Abstract><AbstractText>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.</AbstractText>
</Abstract>
<AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Parks</LastName>
<ForeName>Tom</ForeName>
<Initials>T</Initials>
<Identifier Source="ORCID">http://orcid.org/0000-0002-1163-8654</Identifier>
<AffiliationInfo><Affiliation>Wellcome Trust Centre for Human Genetics, University of Oxford, Roosevelt Drive, Oxford OX3 7BN, UK.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Mirabel</LastName>
<ForeName>Mariana M</ForeName>
<Initials>MM</Initials>
<AffiliationInfo><Affiliation>Paris Centre de Recherche Cardiovasculaire, Institut National de la Santé et de la Recherche Médicale, Hôpital Européen Georges Pompidou, 56, rue Leblanc, 75908 Paris, France.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Kado</LastName>
<ForeName>Joseph</ForeName>
<Initials>J</Initials>
<AffiliationInfo><Affiliation>Department of Paediatrics, Ministry of Health and Medical Services, Colonial War Memorial Hospital, Brown Street, Suva, Fiji.</Affiliation>
</AffiliationInfo>
<AffiliationInfo><Affiliation>College of Medicine, Nursing &Health Sciences, Fiji National University, Brown Street, Suva, Fiji.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Auckland</LastName>
<ForeName>Kathryn</ForeName>
<Initials>K</Initials>
<AffiliationInfo><Affiliation>Wellcome Trust Centre for Human Genetics, University of Oxford, Roosevelt Drive, Oxford OX3 7BN, UK.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Nowak</LastName>
<ForeName>Jaroslaw</ForeName>
<Initials>J</Initials>
<AffiliationInfo><Affiliation>Department of Statistics, University of Oxford, Peter Medawar Building for Pathogen Research, Oxford OX1 3S, UK.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Rautanen</LastName>
<ForeName>Anna</ForeName>
<Initials>A</Initials>
<AffiliationInfo><Affiliation>Wellcome Trust Centre for Human Genetics, University of Oxford, Roosevelt Drive, Oxford OX3 7BN, UK.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Mentzer</LastName>
<ForeName>Alexander J</ForeName>
<Initials>AJ</Initials>
<Identifier Source="ORCID">http://orcid.org/0000-0002-4502-2209</Identifier>
<AffiliationInfo><Affiliation>Wellcome Trust Centre for Human Genetics, University of Oxford, Roosevelt Drive, Oxford OX3 7BN, UK.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Marijon</LastName>
<ForeName>Eloi</ForeName>
<Initials>E</Initials>
<AffiliationInfo><Affiliation>Paris Centre de Recherche Cardiovasculaire, Institut National de la Santé et de la Recherche Médicale, Hôpital Européen Georges Pompidou, 56, rue Leblanc, 75908 Paris, France.</Affiliation>
</AffiliationInfo>
<AffiliationInfo><Affiliation>Faculté de Médecine Paris Descartes, Université Paris Descartes, 15, rue de l'école de medicine, 75006 Paris, France.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Jouven</LastName>
<ForeName>Xavier</ForeName>
<Initials>X</Initials>
<AffiliationInfo><Affiliation>Paris Centre de Recherche Cardiovasculaire, Institut National de la Santé et de la Recherche Médicale, Hôpital Européen Georges Pompidou, 56, rue Leblanc, 75908 Paris, France.</Affiliation>
</AffiliationInfo>
<AffiliationInfo><Affiliation>Faculté de Médecine Paris Descartes, Université Paris Descartes, 15, rue de l'école de medicine, 75006 Paris, France.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Perman</LastName>
<ForeName>Mai Ling</ForeName>
<Initials>ML</Initials>
<AffiliationInfo><Affiliation>College of Medicine, Nursing &Health Sciences, Fiji National University, Brown Street, Suva, Fiji.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Cua</LastName>
<ForeName>Tuliana</ForeName>
<Initials>T</Initials>
<AffiliationInfo><Affiliation>Rheumatic Heart Disease Control Programme, Ministry of Health and Medical Services, Colonial War Memorial Hospital, Brown Street, Suva, Fiji.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Kauwe</LastName>
<ForeName>John K</ForeName>
<Initials>JK</Initials>
<AffiliationInfo><Affiliation>College of Life Sciences, Brigham Young University, 4146 Life Sciences Building, Provo, Utah 84602, USA.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Allen</LastName>
<ForeName>John B</ForeName>
<Initials>JB</Initials>
<AffiliationInfo><Affiliation>College of Life Sciences, Brigham Young University, 4146 Life Sciences Building, Provo, Utah 84602, USA.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Taylor</LastName>
<ForeName>Henry</ForeName>
<Initials>H</Initials>
<AffiliationInfo><Affiliation>Rheumatic Heart Disease Control Programme, Samoa Ministry of Health, Moto'otua, Ifiifi Street, Apia, Samoa.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Robson</LastName>
<ForeName>Kathryn J</ForeName>
<Initials>KJ</Initials>
<AffiliationInfo><Affiliation>MRC Weatherall Institute of Molecular Medicine, University of Oxford, John Radcliffe Hospital, Headington, Oxford OX3 9DS, UK.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Deane</LastName>
<ForeName>Charlotte M</ForeName>
<Initials>CM</Initials>
<Identifier Source="ORCID">http://orcid.org/0000-0003-1388-2252</Identifier>
<AffiliationInfo><Affiliation>Department of Statistics, University of Oxford, Peter Medawar Building for Pathogen Research, Oxford OX1 3S, UK.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Steer</LastName>
<ForeName>Andrew C</ForeName>
<Initials>AC</Initials>
<AffiliationInfo><Affiliation>Centre for International Child Health, University of Melbourne, 50 Flemington Road, Parkville, Melbourne Victoria 3052, Australia.</Affiliation>
</AffiliationInfo>
<AffiliationInfo><Affiliation>Murdoch Children's Research Institute, 50 Flemington Road, Parkville, Melbourne, Victoria 3052, Australia.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Hill</LastName>
<ForeName>Adrian V S</ForeName>
<Initials>AVS</Initials>
<AffiliationInfo><Affiliation>Wellcome Trust Centre for Human Genetics, University of Oxford, Roosevelt Drive, Oxford OX3 7BN, UK.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><CollectiveName>Pacific Islands Rheumatic Heart Disease Genetics Network</CollectiveName>
</Author>
</AuthorList>
<Language>eng</Language>
<GrantList CompleteYN="Y"><Grant><Agency>Wellcome Trust</Agency>
<Country>United Kingdom</Country>
</Grant>
</GrantList>
<PublicationTypeList><PublicationType UI="D016428">Journal Article</PublicationType>
</PublicationTypeList>
<ArticleDate DateType="Electronic"><Year>2017</Year>
<Month>05</Month>
<Day>11</Day>
</ArticleDate>
</Article>
<MedlineJournalInfo><Country>England</Country>
<MedlineTA>Nat Commun</MedlineTA>
<NlmUniqueID>101528555</NlmUniqueID>
<ISSNLinking>2041-1723</ISSNLinking>
</MedlineJournalInfo>
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<InvestigatorList><Investigator ValidYN="Y"><LastName>Allen</LastName>
<ForeName>Lori</ForeName>
<Initials>L</Initials>
</Investigator>
<Investigator ValidYN="Y"><LastName>Allen</LastName>
<ForeName>Marvin</ForeName>
<Initials>M</Initials>
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<Investigator ValidYN="Y"><LastName>Braunstein</LastName>
<ForeName>Corinne</ForeName>
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</Investigator>
<Investigator ValidYN="Y"><LastName>Colquhoun</LastName>
<ForeName>Samantha M</ForeName>
<Initials>SM</Initials>
</Investigator>
<Investigator ValidYN="Y"><LastName>Jewine</LastName>
<ForeName>Aurélia</ForeName>
<Initials>A</Initials>
</Investigator>
<Investigator ValidYN="Y"><LastName>Ah Kee</LastName>
<ForeName>Maureen</ForeName>
<Initials>M</Initials>
</Investigator>
<Investigator ValidYN="Y"><LastName>Kumar</LastName>
<ForeName>Rina</ForeName>
<Initials>R</Initials>
</Investigator>
<Investigator ValidYN="Y"><LastName>John Martin</LastName>
<ForeName>William</ForeName>
<Initials>W</Initials>
</Investigator>
<Investigator ValidYN="Y"><LastName>Mataika</LastName>
<ForeName>Reapi</ForeName>
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<Investigator ValidYN="Y"><LastName>Nadra</LastName>
<ForeName>Marie</ForeName>
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<Investigator ValidYN="Y"><LastName>Nadu</LastName>
<ForeName>Shahin</ForeName>
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<Investigator ValidYN="Y"><LastName>Naseri</LastName>
<ForeName>Take</ForeName>
<Initials>T</Initials>
</Investigator>
<Investigator ValidYN="Y"><LastName>Noël</LastName>
<ForeName>Baptiste</ForeName>
<Initials>B</Initials>
</Investigator>
<Investigator ValidYN="Y"><LastName>Simon</LastName>
<ForeName>Nathalie</ForeName>
<Initials>N</Initials>
</Investigator>
<Investigator ValidYN="Y"><LastName>Ward</LastName>
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<PubMedPubDate PubStatus="accepted"><Year>2017</Year>
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