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Genome-wide association study identifies loci on 12q24 and 13q32 associated with Tetralogy of Fallot

Identifieur interne : 004684 ( Main/Exploration ); précédent : 004683; suivant : 004685

Genome-wide association study identifies loci on 12q24 and 13q32 associated with Tetralogy of Fallot

Auteurs : Heather J. Cordell [Royaume-Uni] ; Ana Töpf [Royaume-Uni] ; Chrysovalanto Mamasoula [Royaume-Uni] ; Alex V. Postma [Pays-Bas] ; Jamie Bentham [Royaume-Uni] ; Diana Zelenika [France] ; Simon Heath [France, Espagne] ; Gillian Blue [Australie] ; Catherine Cosgrove [Royaume-Uni] ; Javier Granados Riveron [Royaume-Uni] ; Rebecca Darlay [Royaume-Uni] ; Rachel Soemedi [Royaume-Uni] ; Ian J. Wilson [Royaume-Uni] ; Kristin L. Ayers [Royaume-Uni] ; Thahira J. Rahman [Royaume-Uni] ; Darroch Hall [Royaume-Uni] ; Barbara J. M. Mulder [Pays-Bas] ; Aelko H. Zwinderman [Pays-Bas] ; Klaartje Van Engelen [Pays-Bas] ; J. David Brook [Royaume-Uni] ; Kerry Setchfield [Royaume-Uni] ; Frances A. Bu'Lock [Royaume-Uni] ; Chris Thornborough [Royaume-Uni] ; John O'Sullivan [Royaume-Uni] ; A. Graham Stuart [Royaume-Uni] ; Jonathan Parsons [Royaume-Uni] ; Shoumo Bhattacharya [Royaume-Uni] ; David Winlaw [Australie] ; Seema Mital [Canada] ; Marc Gewillig ; Jeroen Breckpot [Belgique] ; Koen Devriendt [Belgique] ; Antoon F. M. Moorman [Pays-Bas] ; Anita Rauch [Suisse] ; G. Mark Lathrop [France] ; Bernard D. Keavney [Royaume-Uni] ; Judith A. Goodship [Royaume-Uni]

Source :

RBID : PMC:3596849

Abstract

We conducted a genome-wide association study to search for risk alleles associated with Tetralogy of Fallot (TOF), using a northern European discovery set of 835 cases and 5159 controls. A region on chromosome 12q24 was associated (P = 1.4 × 10−7) and replicated convincingly (P = 3.9 × 10−5) in 798 cases and 2931 controls [per allele odds ratio (OR) = 1.27 in replication cohort, P = 7.7 × 10−11 in combined populations]. Single nucleotide polymorphisms in the glypican 5 gene on chromosome 13q32 were also associated (P = 1.7 × 10−7) and replicated convincingly (P = 1.2 × 10−5) in 789 cases and 2927 controls (per allele OR = 1.31 in replication cohort, P = 3.03 × 10−11 in combined populations). Four additional regions on chromosomes 10, 15 and 16 showed suggestive association accompanied by nominal replication. This study, the first genome-wide association study of a congenital heart malformation phenotype, provides evidence that common genetic variation influences the risk of TOF.


Url:
DOI: 10.1093/hmg/dds552
PubMed: 23297363
PubMed Central: 3596849


Affiliations:


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Le document en format XML

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<name sortKey="Mamasoula, Chrysovalanto" sort="Mamasoula, Chrysovalanto" uniqKey="Mamasoula C" first="Chrysovalanto" last="Mamasoula">Chrysovalanto Mamasoula</name>
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<country>France</country>
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<country xml:lang="fr">France</country>
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<name sortKey="Heath, Simon" sort="Heath, Simon" uniqKey="Heath S" first="Simon" last="Heath">Simon Heath</name>
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<addr-line>Evry</addr-line>
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<country xml:lang="fr">France</country>
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<institution>Centro Nacional de Análisis Genómico</institution>
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<country xml:lang="fr">Espagne</country>
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<addr-line>Oxford OX1 2JD</addr-line>
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<country>UK</country>
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<country xml:lang="fr">Royaume-Uni</country>
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<name sortKey="Granados Riveron, Javier" sort="Granados Riveron, Javier" uniqKey="Granados Riveron J" first="Javier" last="Granados Riveron">Javier Granados Riveron</name>
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<nlm:aff id="af8">
<addr-line>Institute of Genetics</addr-line>
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<institution>Nottingham University</institution>
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<country>UK</country>
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<country xml:lang="fr">Royaume-Uni</country>
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<name sortKey="Darlay, Rebecca" sort="Darlay, Rebecca" uniqKey="Darlay R" first="Rebecca" last="Darlay">Rebecca Darlay</name>
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<country>UK</country>
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<country xml:lang="fr">Royaume-Uni</country>
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<name sortKey="Soemedi, Rachel" sort="Soemedi, Rachel" uniqKey="Soemedi R" first="Rachel" last="Soemedi">Rachel Soemedi</name>
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<addr-line>Institute of Genetic Medicine</addr-line>
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<institution>Newcastle University</institution>
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<addr-line>Newcastle upon Tyne NE1 3BZ</addr-line>
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<country>UK</country>
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<country xml:lang="fr">Royaume-Uni</country>
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<name sortKey="Wilson, Ian J" sort="Wilson, Ian J" uniqKey="Wilson I" first="Ian J." last="Wilson">Ian J. Wilson</name>
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<addr-line>Newcastle upon Tyne NE1 3BZ</addr-line>
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<country xml:lang="fr">Royaume-Uni</country>
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<name sortKey="Ayers, Kristin L" sort="Ayers, Kristin L" uniqKey="Ayers K" first="Kristin L." last="Ayers">Kristin L. Ayers</name>
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<nlm:aff id="af1">
<addr-line>Institute of Genetic Medicine</addr-line>
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<institution>Newcastle University</institution>
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<addr-line>Newcastle upon Tyne NE1 3BZ</addr-line>
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<country>UK</country>
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<country xml:lang="fr">Royaume-Uni</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
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<name sortKey="Rahman, Thahira J" sort="Rahman, Thahira J" uniqKey="Rahman T" first="Thahira J." last="Rahman">Thahira J. Rahman</name>
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<nlm:aff id="af1">
<addr-line>Institute of Genetic Medicine</addr-line>
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<institution>Newcastle University</institution>
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<addr-line>Newcastle upon Tyne NE1 3BZ</addr-line>
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<country>UK</country>
,</nlm:aff>
<country xml:lang="fr">Royaume-Uni</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
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<name sortKey="Hall, Darroch" sort="Hall, Darroch" uniqKey="Hall D" first="Darroch" last="Hall">Darroch Hall</name>
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<addr-line>Institute of Genetic Medicine</addr-line>
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<institution>Newcastle University</institution>
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<country xml:lang="fr">Royaume-Uni</country>
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<name sortKey="Mulder, Barbara J M" sort="Mulder, Barbara J M" uniqKey="Mulder B" first="Barbara J. M." last="Mulder">Barbara J. M. Mulder</name>
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<country xml:lang="fr">Pays-Bas</country>
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<author>
<name sortKey="Zwinderman, Aelko H" sort="Zwinderman, Aelko H" uniqKey="Zwinderman A" first="Aelko H." last="Zwinderman">Aelko H. Zwinderman</name>
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<addr-line>Amsterdam</addr-line>
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<country xml:lang="fr">Pays-Bas</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
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<name sortKey="Van Engelen, Klaartje" sort="Van Engelen, Klaartje" uniqKey="Van Engelen K" first="Klaartje" last="Van Engelen">Klaartje Van Engelen</name>
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<addr-line>Amsterdam</addr-line>
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<country>The Netherlands</country>
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<country xml:lang="fr">Pays-Bas</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
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</author>
<author>
<name sortKey="Brook, J David" sort="Brook, J David" uniqKey="Brook J" first="J. David" last="Brook">J. David Brook</name>
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<nlm:aff id="af8">
<addr-line>Institute of Genetics</addr-line>
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<institution>Nottingham University</institution>
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<addr-line>Nottingham NG7 2RD</addr-line>
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<country>UK</country>
,</nlm:aff>
<country xml:lang="fr">Royaume-Uni</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
<author>
<name sortKey="Setchfield, Kerry" sort="Setchfield, Kerry" uniqKey="Setchfield K" first="Kerry" last="Setchfield">Kerry Setchfield</name>
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<nlm:aff id="af8">
<addr-line>Institute of Genetics</addr-line>
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<institution>Nottingham University</institution>
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<addr-line>Nottingham NG7 2RD</addr-line>
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<country>UK</country>
,</nlm:aff>
<country xml:lang="fr">Royaume-Uni</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
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<author>
<name sortKey="Bu Lock, Frances A" sort="Bu Lock, Frances A" uniqKey="Bu Lock F" first="Frances A." last="Bu'Lock">Frances A. Bu'Lock</name>
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<addr-line>Leicester</addr-line>
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<country>UK</country>
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<country xml:lang="fr">Royaume-Uni</country>
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<name sortKey="Thornborough, Chris" sort="Thornborough, Chris" uniqKey="Thornborough C" first="Chris" last="Thornborough">Chris Thornborough</name>
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<addr-line>Leicester</addr-line>
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<country>UK</country>
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<country xml:lang="fr">Royaume-Uni</country>
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</affiliation>
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<author>
<name sortKey="O Sullivan, John" sort="O Sullivan, John" uniqKey="O Sullivan J" first="John" last="O'Sullivan">John O'Sullivan</name>
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<addr-line>Newcastle</addr-line>
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<country>UK</country>
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<country xml:lang="fr">Royaume-Uni</country>
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<author>
<name sortKey="Stuart, A Graham" sort="Stuart, A Graham" uniqKey="Stuart A" first="A. Graham" last="Stuart">A. Graham Stuart</name>
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<addr-line>Bristol</addr-line>
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<country xml:lang="fr">Royaume-Uni</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
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<author>
<name sortKey="Parsons, Jonathan" sort="Parsons, Jonathan" uniqKey="Parsons J" first="Jonathan" last="Parsons">Jonathan Parsons</name>
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<country xml:lang="fr">Royaume-Uni</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
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<author>
<name sortKey="Bhattacharya, Shoumo" sort="Bhattacharya, Shoumo" uniqKey="Bhattacharya S" first="Shoumo" last="Bhattacharya">Shoumo Bhattacharya</name>
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<nlm:aff id="af3">
<addr-line>Department of Cardiovascular Medicine</addr-line>
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<institution>Oxford University</institution>
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<addr-line>Oxford OX1 2JD</addr-line>
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<country>UK</country>
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<country xml:lang="fr">Royaume-Uni</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
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<author>
<name sortKey="Winlaw, David" sort="Winlaw, David" uniqKey="Winlaw D" first="David" last="Winlaw">David Winlaw</name>
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<addr-line>Westmead, New South Wales</addr-line>
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<country>Australia</country>
,</nlm:aff>
<country xml:lang="fr">Australie</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
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</author>
<author>
<name sortKey="Mital, Seema" sort="Mital, Seema" uniqKey="Mital S" first="Seema" last="Mital">Seema Mital</name>
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<nlm:aff id="af13">
<institution>Hospital for Sick Children</institution>
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<addr-line>Toronto</addr-line>
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<country>Canada</country>
,</nlm:aff>
<country xml:lang="fr">Canada</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
<author>
<name sortKey="Gewillig, Marc" sort="Gewillig, Marc" uniqKey="Gewillig M" first="Marc" last="Gewillig">Marc Gewillig</name>
<affiliation>
<nlm:aff id="af14">
<addr-line>Department of Pediatric Cardiology</addr-line>
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</affiliation>
</author>
<author>
<name sortKey="Breckpot, Jeroen" sort="Breckpot, Jeroen" uniqKey="Breckpot J" first="Jeroen" last="Breckpot">Jeroen Breckpot</name>
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<nlm:aff wicri:cut=" and" id="af15">
<addr-line>Center for Human Genetics</addr-line>
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<institution>University of Leuven</institution>
,
<addr-line>Leuven 3000</addr-line>
,
<country>Belgium</country>
</nlm:aff>
<country xml:lang="fr">Belgique</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
<author>
<name sortKey="Devriendt, Koen" sort="Devriendt, Koen" uniqKey="Devriendt K" first="Koen" last="Devriendt">Koen Devriendt</name>
<affiliation wicri:level="1">
<nlm:aff wicri:cut=" and" id="af15">
<addr-line>Center for Human Genetics</addr-line>
,
<institution>University of Leuven</institution>
,
<addr-line>Leuven 3000</addr-line>
,
<country>Belgium</country>
</nlm:aff>
<country xml:lang="fr">Belgique</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
<author>
<name sortKey="Moorman, Antoon F M" sort="Moorman, Antoon F M" uniqKey="Moorman A" first="Antoon F. M." last="Moorman">Antoon F. M. Moorman</name>
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<nlm:aff id="af2">
<institution>Academic Medical Center</institution>
,
<addr-line>Amsterdam</addr-line>
,
<country>The Netherlands</country>
,</nlm:aff>
<country xml:lang="fr">Pays-Bas</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
<author>
<name sortKey="Rauch, Anita" sort="Rauch, Anita" uniqKey="Rauch A" first="Anita" last="Rauch">Anita Rauch</name>
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<nlm:aff id="af16">
<addr-line>Institute of Medical Genetics</addr-line>
,
<institution>University of Zurich</institution>
,
<addr-line>Zurich 8006</addr-line>
,
<country>Switzerland</country>
</nlm:aff>
<country xml:lang="fr">Suisse</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
<author>
<name sortKey="Lathrop, G Mark" sort="Lathrop, G Mark" uniqKey="Lathrop G" first="G. Mark" last="Lathrop">G. Mark Lathrop</name>
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<nlm:aff id="af4">
<addr-line>Institut Genomique, Centre National de Genotypage</addr-line>
,
<institution>Commisariat à l’énergie Atomique (CEA)</institution>
,
<addr-line>Evry</addr-line>
,
<country>France</country>
,</nlm:aff>
<country xml:lang="fr">France</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
<affiliation wicri:level="1">
<nlm:aff id="af5">
<addr-line>Centre d'Etude du Polymorphisme Humain</addr-line>
,
<institution>Fondation Jean Dausset</institution>
,
<addr-line>Paris 75010</addr-line>
,
<country>France</country>
,</nlm:aff>
<country xml:lang="fr">France</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
<author>
<name sortKey="Keavney, Bernard D" sort="Keavney, Bernard D" uniqKey="Keavney B" first="Bernard D." last="Keavney">Bernard D. Keavney</name>
<affiliation wicri:level="1">
<nlm:aff id="af1">
<addr-line>Institute of Genetic Medicine</addr-line>
,
<institution>Newcastle University</institution>
,
<addr-line>Newcastle upon Tyne NE1 3BZ</addr-line>
,
<country>UK</country>
,</nlm:aff>
<country xml:lang="fr">Royaume-Uni</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
<author>
<name sortKey="Goodship, Judith A" sort="Goodship, Judith A" uniqKey="Goodship J" first="Judith A." last="Goodship">Judith A. Goodship</name>
<affiliation wicri:level="1">
<nlm:aff id="af1">
<addr-line>Institute of Genetic Medicine</addr-line>
,
<institution>Newcastle University</institution>
,
<addr-line>Newcastle upon Tyne NE1 3BZ</addr-line>
,
<country>UK</country>
,</nlm:aff>
<country xml:lang="fr">Royaume-Uni</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
</titleStmt>
<publicationStmt>
<idno type="wicri:source">PMC</idno>
<idno type="pmid">23297363</idno>
<idno type="pmc">3596849</idno>
<idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3596849</idno>
<idno type="RBID">PMC:3596849</idno>
<idno type="doi">10.1093/hmg/dds552</idno>
<date when="2013">2013</date>
<idno type="wicri:Area/Pmc/Corpus">002576</idno>
<idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Corpus" wicri:corpus="PMC">002576</idno>
<idno type="wicri:Area/Pmc/Curation">002426</idno>
<idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Curation">002426</idno>
<idno type="wicri:Area/Pmc/Checkpoint">001B08</idno>
<idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Checkpoint">001B08</idno>
<idno type="wicri:Area/Ncbi/Merge">001086</idno>
<idno type="wicri:Area/Ncbi/Curation">001086</idno>
<idno type="wicri:Area/Ncbi/Checkpoint">001086</idno>
<idno type="wicri:doubleKey">0964-6906:2013:Cordell H:genome:wide:association</idno>
<idno type="wicri:Area/Main/Merge">004795</idno>
<idno type="wicri:Area/Main/Curation">004684</idno>
<idno type="wicri:Area/Main/Exploration">004684</idno>
</publicationStmt>
<sourceDesc>
<biblStruct>
<analytic>
<title xml:lang="en" level="a" type="main">Genome-wide association study identifies loci on 12q24 and 13q32 associated with Tetralogy of Fallot</title>
<author>
<name sortKey="Cordell, Heather J" sort="Cordell, Heather J" uniqKey="Cordell H" first="Heather J." last="Cordell">Heather J. Cordell</name>
<affiliation wicri:level="1">
<nlm:aff id="af1">
<addr-line>Institute of Genetic Medicine</addr-line>
,
<institution>Newcastle University</institution>
,
<addr-line>Newcastle upon Tyne NE1 3BZ</addr-line>
,
<country>UK</country>
,</nlm:aff>
<country xml:lang="fr">Royaume-Uni</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
<author>
<name sortKey="Topf, Ana" sort="Topf, Ana" uniqKey="Topf A" first="Ana" last="Töpf">Ana Töpf</name>
<affiliation wicri:level="1">
<nlm:aff id="af1">
<addr-line>Institute of Genetic Medicine</addr-line>
,
<institution>Newcastle University</institution>
,
<addr-line>Newcastle upon Tyne NE1 3BZ</addr-line>
,
<country>UK</country>
,</nlm:aff>
<country xml:lang="fr">Royaume-Uni</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
<author>
<name sortKey="Mamasoula, Chrysovalanto" sort="Mamasoula, Chrysovalanto" uniqKey="Mamasoula C" first="Chrysovalanto" last="Mamasoula">Chrysovalanto Mamasoula</name>
<affiliation wicri:level="1">
<nlm:aff id="af1">
<addr-line>Institute of Genetic Medicine</addr-line>
,
<institution>Newcastle University</institution>
,
<addr-line>Newcastle upon Tyne NE1 3BZ</addr-line>
,
<country>UK</country>
,</nlm:aff>
<country xml:lang="fr">Royaume-Uni</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
<author>
<name sortKey="Postma, Alex V" sort="Postma, Alex V" uniqKey="Postma A" first="Alex V." last="Postma">Alex V. Postma</name>
<affiliation wicri:level="1">
<nlm:aff id="af2">
<institution>Academic Medical Center</institution>
,
<addr-line>Amsterdam</addr-line>
,
<country>The Netherlands</country>
,</nlm:aff>
<country xml:lang="fr">Pays-Bas</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
<author>
<name sortKey="Bentham, Jamie" sort="Bentham, Jamie" uniqKey="Bentham J" first="Jamie" last="Bentham">Jamie Bentham</name>
<affiliation wicri:level="1">
<nlm:aff id="af3">
<addr-line>Department of Cardiovascular Medicine</addr-line>
,
<institution>Oxford University</institution>
,
<addr-line>Oxford OX1 2JD</addr-line>
,
<country>UK</country>
,</nlm:aff>
<country xml:lang="fr">Royaume-Uni</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
<author>
<name sortKey="Zelenika, Diana" sort="Zelenika, Diana" uniqKey="Zelenika D" first="Diana" last="Zelenika">Diana Zelenika</name>
<affiliation wicri:level="1">
<nlm:aff id="af4">
<addr-line>Institut Genomique, Centre National de Genotypage</addr-line>
,
<institution>Commisariat à l’énergie Atomique (CEA)</institution>
,
<addr-line>Evry</addr-line>
,
<country>France</country>
,</nlm:aff>
<country xml:lang="fr">France</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
<affiliation wicri:level="1">
<nlm:aff id="af5">
<addr-line>Centre d'Etude du Polymorphisme Humain</addr-line>
,
<institution>Fondation Jean Dausset</institution>
,
<addr-line>Paris 75010</addr-line>
,
<country>France</country>
,</nlm:aff>
<country xml:lang="fr">France</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
<author>
<name sortKey="Heath, Simon" sort="Heath, Simon" uniqKey="Heath S" first="Simon" last="Heath">Simon Heath</name>
<affiliation wicri:level="1">
<nlm:aff id="af4">
<addr-line>Institut Genomique, Centre National de Genotypage</addr-line>
,
<institution>Commisariat à l’énergie Atomique (CEA)</institution>
,
<addr-line>Evry</addr-line>
,
<country>France</country>
,</nlm:aff>
<country xml:lang="fr">France</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
<affiliation wicri:level="1">
<nlm:aff id="af6">
<institution>Centro Nacional de Análisis Genómico</institution>
,
<addr-line>Barcelona</addr-line>
,
<country>Spain</country>
,</nlm:aff>
<country xml:lang="fr">Espagne</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
<author>
<name sortKey="Blue, Gillian" sort="Blue, Gillian" uniqKey="Blue G" first="Gillian" last="Blue">Gillian Blue</name>
<affiliation wicri:level="1">
<nlm:aff id="af7">
<institution>The Children's Hospital at Westmead</institution>
,
<addr-line>Westmead, New South Wales</addr-line>
,
<country>Australia</country>
,</nlm:aff>
<country xml:lang="fr">Australie</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
<author>
<name sortKey="Cosgrove, Catherine" sort="Cosgrove, Catherine" uniqKey="Cosgrove C" first="Catherine" last="Cosgrove">Catherine Cosgrove</name>
<affiliation wicri:level="1">
<nlm:aff id="af3">
<addr-line>Department of Cardiovascular Medicine</addr-line>
,
<institution>Oxford University</institution>
,
<addr-line>Oxford OX1 2JD</addr-line>
,
<country>UK</country>
,</nlm:aff>
<country xml:lang="fr">Royaume-Uni</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
<author>
<name sortKey="Granados Riveron, Javier" sort="Granados Riveron, Javier" uniqKey="Granados Riveron J" first="Javier" last="Granados Riveron">Javier Granados Riveron</name>
<affiliation wicri:level="1">
<nlm:aff id="af8">
<addr-line>Institute of Genetics</addr-line>
,
<institution>Nottingham University</institution>
,
<addr-line>Nottingham NG7 2RD</addr-line>
,
<country>UK</country>
,</nlm:aff>
<country xml:lang="fr">Royaume-Uni</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
<author>
<name sortKey="Darlay, Rebecca" sort="Darlay, Rebecca" uniqKey="Darlay R" first="Rebecca" last="Darlay">Rebecca Darlay</name>
<affiliation wicri:level="1">
<nlm:aff id="af1">
<addr-line>Institute of Genetic Medicine</addr-line>
,
<institution>Newcastle University</institution>
,
<addr-line>Newcastle upon Tyne NE1 3BZ</addr-line>
,
<country>UK</country>
,</nlm:aff>
<country xml:lang="fr">Royaume-Uni</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
<author>
<name sortKey="Soemedi, Rachel" sort="Soemedi, Rachel" uniqKey="Soemedi R" first="Rachel" last="Soemedi">Rachel Soemedi</name>
<affiliation wicri:level="1">
<nlm:aff id="af1">
<addr-line>Institute of Genetic Medicine</addr-line>
,
<institution>Newcastle University</institution>
,
<addr-line>Newcastle upon Tyne NE1 3BZ</addr-line>
,
<country>UK</country>
,</nlm:aff>
<country xml:lang="fr">Royaume-Uni</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
<author>
<name sortKey="Wilson, Ian J" sort="Wilson, Ian J" uniqKey="Wilson I" first="Ian J." last="Wilson">Ian J. Wilson</name>
<affiliation wicri:level="1">
<nlm:aff id="af1">
<addr-line>Institute of Genetic Medicine</addr-line>
,
<institution>Newcastle University</institution>
,
<addr-line>Newcastle upon Tyne NE1 3BZ</addr-line>
,
<country>UK</country>
,</nlm:aff>
<country xml:lang="fr">Royaume-Uni</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
<author>
<name sortKey="Ayers, Kristin L" sort="Ayers, Kristin L" uniqKey="Ayers K" first="Kristin L." last="Ayers">Kristin L. Ayers</name>
<affiliation wicri:level="1">
<nlm:aff id="af1">
<addr-line>Institute of Genetic Medicine</addr-line>
,
<institution>Newcastle University</institution>
,
<addr-line>Newcastle upon Tyne NE1 3BZ</addr-line>
,
<country>UK</country>
,</nlm:aff>
<country xml:lang="fr">Royaume-Uni</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
<author>
<name sortKey="Rahman, Thahira J" sort="Rahman, Thahira J" uniqKey="Rahman T" first="Thahira J." last="Rahman">Thahira J. Rahman</name>
<affiliation wicri:level="1">
<nlm:aff id="af1">
<addr-line>Institute of Genetic Medicine</addr-line>
,
<institution>Newcastle University</institution>
,
<addr-line>Newcastle upon Tyne NE1 3BZ</addr-line>
,
<country>UK</country>
,</nlm:aff>
<country xml:lang="fr">Royaume-Uni</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
<author>
<name sortKey="Hall, Darroch" sort="Hall, Darroch" uniqKey="Hall D" first="Darroch" last="Hall">Darroch Hall</name>
<affiliation wicri:level="1">
<nlm:aff id="af1">
<addr-line>Institute of Genetic Medicine</addr-line>
,
<institution>Newcastle University</institution>
,
<addr-line>Newcastle upon Tyne NE1 3BZ</addr-line>
,
<country>UK</country>
,</nlm:aff>
<country xml:lang="fr">Royaume-Uni</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
<author>
<name sortKey="Mulder, Barbara J M" sort="Mulder, Barbara J M" uniqKey="Mulder B" first="Barbara J. M." last="Mulder">Barbara J. M. Mulder</name>
<affiliation wicri:level="1">
<nlm:aff id="af2">
<institution>Academic Medical Center</institution>
,
<addr-line>Amsterdam</addr-line>
,
<country>The Netherlands</country>
,</nlm:aff>
<country xml:lang="fr">Pays-Bas</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
<author>
<name sortKey="Zwinderman, Aelko H" sort="Zwinderman, Aelko H" uniqKey="Zwinderman A" first="Aelko H." last="Zwinderman">Aelko H. Zwinderman</name>
<affiliation wicri:level="1">
<nlm:aff id="af2">
<institution>Academic Medical Center</institution>
,
<addr-line>Amsterdam</addr-line>
,
<country>The Netherlands</country>
,</nlm:aff>
<country xml:lang="fr">Pays-Bas</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
<author>
<name sortKey="Van Engelen, Klaartje" sort="Van Engelen, Klaartje" uniqKey="Van Engelen K" first="Klaartje" last="Van Engelen">Klaartje Van Engelen</name>
<affiliation wicri:level="1">
<nlm:aff id="af2">
<institution>Academic Medical Center</institution>
,
<addr-line>Amsterdam</addr-line>
,
<country>The Netherlands</country>
,</nlm:aff>
<country xml:lang="fr">Pays-Bas</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
<author>
<name sortKey="Brook, J David" sort="Brook, J David" uniqKey="Brook J" first="J. David" last="Brook">J. David Brook</name>
<affiliation wicri:level="1">
<nlm:aff id="af8">
<addr-line>Institute of Genetics</addr-line>
,
<institution>Nottingham University</institution>
,
<addr-line>Nottingham NG7 2RD</addr-line>
,
<country>UK</country>
,</nlm:aff>
<country xml:lang="fr">Royaume-Uni</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
<author>
<name sortKey="Setchfield, Kerry" sort="Setchfield, Kerry" uniqKey="Setchfield K" first="Kerry" last="Setchfield">Kerry Setchfield</name>
<affiliation wicri:level="1">
<nlm:aff id="af8">
<addr-line>Institute of Genetics</addr-line>
,
<institution>Nottingham University</institution>
,
<addr-line>Nottingham NG7 2RD</addr-line>
,
<country>UK</country>
,</nlm:aff>
<country xml:lang="fr">Royaume-Uni</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
<author>
<name sortKey="Bu Lock, Frances A" sort="Bu Lock, Frances A" uniqKey="Bu Lock F" first="Frances A." last="Bu'Lock">Frances A. Bu'Lock</name>
<affiliation wicri:level="1">
<nlm:aff id="af9">
<institution>University Hospitals of Leicester NHS Trust</institution>
,
<addr-line>Leicester</addr-line>
,
<country>UK</country>
,</nlm:aff>
<country xml:lang="fr">Royaume-Uni</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
<author>
<name sortKey="Thornborough, Chris" sort="Thornborough, Chris" uniqKey="Thornborough C" first="Chris" last="Thornborough">Chris Thornborough</name>
<affiliation wicri:level="1">
<nlm:aff id="af9">
<institution>University Hospitals of Leicester NHS Trust</institution>
,
<addr-line>Leicester</addr-line>
,
<country>UK</country>
,</nlm:aff>
<country xml:lang="fr">Royaume-Uni</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
<author>
<name sortKey="O Sullivan, John" sort="O Sullivan, John" uniqKey="O Sullivan J" first="John" last="O'Sullivan">John O'Sullivan</name>
<affiliation wicri:level="1">
<nlm:aff id="af10">
<institution>Newcastle upon Tyne Hospitals NHS Foundation Trust</institution>
,
<addr-line>Newcastle</addr-line>
,
<country>UK</country>
,</nlm:aff>
<country xml:lang="fr">Royaume-Uni</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
<author>
<name sortKey="Stuart, A Graham" sort="Stuart, A Graham" uniqKey="Stuart A" first="A. Graham" last="Stuart">A. Graham Stuart</name>
<affiliation wicri:level="1">
<nlm:aff id="af11">
<institution>Bristol Royal Hospital for Children</institution>
,
<addr-line>Bristol</addr-line>
,
<country>UK</country>
,</nlm:aff>
<country xml:lang="fr">Royaume-Uni</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
<author>
<name sortKey="Parsons, Jonathan" sort="Parsons, Jonathan" uniqKey="Parsons J" first="Jonathan" last="Parsons">Jonathan Parsons</name>
<affiliation wicri:level="1">
<nlm:aff id="af12">
<institution>Leeds Teaching Hospitals NHS Trust</institution>
,
<addr-line>Leeds</addr-line>
,
<country>UK</country>
,</nlm:aff>
<country xml:lang="fr">Royaume-Uni</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
<author>
<name sortKey="Bhattacharya, Shoumo" sort="Bhattacharya, Shoumo" uniqKey="Bhattacharya S" first="Shoumo" last="Bhattacharya">Shoumo Bhattacharya</name>
<affiliation wicri:level="1">
<nlm:aff id="af3">
<addr-line>Department of Cardiovascular Medicine</addr-line>
,
<institution>Oxford University</institution>
,
<addr-line>Oxford OX1 2JD</addr-line>
,
<country>UK</country>
,</nlm:aff>
<country xml:lang="fr">Royaume-Uni</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
<author>
<name sortKey="Winlaw, David" sort="Winlaw, David" uniqKey="Winlaw D" first="David" last="Winlaw">David Winlaw</name>
<affiliation wicri:level="1">
<nlm:aff id="af7">
<institution>The Children's Hospital at Westmead</institution>
,
<addr-line>Westmead, New South Wales</addr-line>
,
<country>Australia</country>
,</nlm:aff>
<country xml:lang="fr">Australie</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
<author>
<name sortKey="Mital, Seema" sort="Mital, Seema" uniqKey="Mital S" first="Seema" last="Mital">Seema Mital</name>
<affiliation wicri:level="1">
<nlm:aff id="af13">
<institution>Hospital for Sick Children</institution>
,
<addr-line>Toronto</addr-line>
,
<country>Canada</country>
,</nlm:aff>
<country xml:lang="fr">Canada</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
<author>
<name sortKey="Gewillig, Marc" sort="Gewillig, Marc" uniqKey="Gewillig M" first="Marc" last="Gewillig">Marc Gewillig</name>
<affiliation>
<nlm:aff id="af14">
<addr-line>Department of Pediatric Cardiology</addr-line>
,</nlm:aff>
</affiliation>
</author>
<author>
<name sortKey="Breckpot, Jeroen" sort="Breckpot, Jeroen" uniqKey="Breckpot J" first="Jeroen" last="Breckpot">Jeroen Breckpot</name>
<affiliation wicri:level="1">
<nlm:aff wicri:cut=" and" id="af15">
<addr-line>Center for Human Genetics</addr-line>
,
<institution>University of Leuven</institution>
,
<addr-line>Leuven 3000</addr-line>
,
<country>Belgium</country>
</nlm:aff>
<country xml:lang="fr">Belgique</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
<author>
<name sortKey="Devriendt, Koen" sort="Devriendt, Koen" uniqKey="Devriendt K" first="Koen" last="Devriendt">Koen Devriendt</name>
<affiliation wicri:level="1">
<nlm:aff wicri:cut=" and" id="af15">
<addr-line>Center for Human Genetics</addr-line>
,
<institution>University of Leuven</institution>
,
<addr-line>Leuven 3000</addr-line>
,
<country>Belgium</country>
</nlm:aff>
<country xml:lang="fr">Belgique</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
<author>
<name sortKey="Moorman, Antoon F M" sort="Moorman, Antoon F M" uniqKey="Moorman A" first="Antoon F. M." last="Moorman">Antoon F. M. Moorman</name>
<affiliation wicri:level="1">
<nlm:aff id="af2">
<institution>Academic Medical Center</institution>
,
<addr-line>Amsterdam</addr-line>
,
<country>The Netherlands</country>
,</nlm:aff>
<country xml:lang="fr">Pays-Bas</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
<author>
<name sortKey="Rauch, Anita" sort="Rauch, Anita" uniqKey="Rauch A" first="Anita" last="Rauch">Anita Rauch</name>
<affiliation wicri:level="1">
<nlm:aff id="af16">
<addr-line>Institute of Medical Genetics</addr-line>
,
<institution>University of Zurich</institution>
,
<addr-line>Zurich 8006</addr-line>
,
<country>Switzerland</country>
</nlm:aff>
<country xml:lang="fr">Suisse</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
<author>
<name sortKey="Lathrop, G Mark" sort="Lathrop, G Mark" uniqKey="Lathrop G" first="G. Mark" last="Lathrop">G. Mark Lathrop</name>
<affiliation wicri:level="1">
<nlm:aff id="af4">
<addr-line>Institut Genomique, Centre National de Genotypage</addr-line>
,
<institution>Commisariat à l’énergie Atomique (CEA)</institution>
,
<addr-line>Evry</addr-line>
,
<country>France</country>
,</nlm:aff>
<country xml:lang="fr">France</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
<affiliation wicri:level="1">
<nlm:aff id="af5">
<addr-line>Centre d'Etude du Polymorphisme Humain</addr-line>
,
<institution>Fondation Jean Dausset</institution>
,
<addr-line>Paris 75010</addr-line>
,
<country>France</country>
,</nlm:aff>
<country xml:lang="fr">France</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
<author>
<name sortKey="Keavney, Bernard D" sort="Keavney, Bernard D" uniqKey="Keavney B" first="Bernard D." last="Keavney">Bernard D. Keavney</name>
<affiliation wicri:level="1">
<nlm:aff id="af1">
<addr-line>Institute of Genetic Medicine</addr-line>
,
<institution>Newcastle University</institution>
,
<addr-line>Newcastle upon Tyne NE1 3BZ</addr-line>
,
<country>UK</country>
,</nlm:aff>
<country xml:lang="fr">Royaume-Uni</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
<author>
<name sortKey="Goodship, Judith A" sort="Goodship, Judith A" uniqKey="Goodship J" first="Judith A." last="Goodship">Judith A. Goodship</name>
<affiliation wicri:level="1">
<nlm:aff id="af1">
<addr-line>Institute of Genetic Medicine</addr-line>
,
<institution>Newcastle University</institution>
,
<addr-line>Newcastle upon Tyne NE1 3BZ</addr-line>
,
<country>UK</country>
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<country xml:lang="fr">Royaume-Uni</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
</analytic>
<series>
<title level="j">Human Molecular Genetics</title>
<idno type="ISSN">0964-6906</idno>
<idno type="eISSN">1460-2083</idno>
<imprint>
<date when="2013">2013</date>
</imprint>
</series>
</biblStruct>
</sourceDesc>
</fileDesc>
<profileDesc>
<textClass></textClass>
</profileDesc>
</teiHeader>
<front>
<div type="abstract" xml:lang="en">
<p>We conducted a genome-wide association study to search for risk alleles associated with Tetralogy of Fallot (TOF), using a northern European discovery set of 835 cases and 5159 controls. A region on chromosome 12q24 was associated (
<italic>P</italic>
= 1.4 × 10
<sup>−7</sup>
) and replicated convincingly (
<italic>P</italic>
= 3.9 × 10
<sup>−5</sup>
) in 798 cases and 2931 controls [per allele odds ratio (OR) = 1.27 in replication cohort,
<italic>P</italic>
= 7.7 × 10
<sup>−11</sup>
in combined populations]. Single nucleotide polymorphisms in the glypican 5 gene on chromosome 13q32 were also associated (
<italic>P</italic>
= 1.7 × 10
<sup>−7</sup>
) and replicated convincingly (
<italic>P</italic>
= 1.2 × 10
<sup>−5</sup>
) in 789 cases and 2927 controls (per allele OR = 1.31 in replication cohort,
<italic>P</italic>
= 3.03 × 10
<sup>−11</sup>
in combined populations). Four additional regions on chromosomes 10, 15 and 16 showed suggestive association accompanied by nominal replication. This study, the first genome-wide association study of a congenital heart malformation phenotype, provides evidence that common genetic variation influences the risk of TOF.</p>
</div>
</front>
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</author>
<author>
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<name sortKey="Lathrop, G Mark" sort="Lathrop, G Mark" uniqKey="Lathrop G" first="G. Mark" last="Lathrop">G. Mark Lathrop</name>
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