A variant at 9p21.3 functionally implicates CDKN2B in paediatric B-cell precursor acute lymphoblastic leukaemia aetiology
Identifieur interne : 000B54 ( Pmc/Checkpoint ); précédent : 000B53; suivant : 000B55A variant at 9p21.3 functionally implicates CDKN2B in paediatric B-cell precursor acute lymphoblastic leukaemia aetiology
Auteurs : Eric A. Hungate [États-Unis] ; Sapana R. Vora [États-Unis] ; Eric R. Gamazon [États-Unis, Pays-Bas] ; Takaya Moriyama [États-Unis] ; Timothy Best [États-Unis] ; Imge Hulur [États-Unis] ; Younghee Lee [États-Unis] ; Tiffany-Jane Evans [Australie] ; Eva Ellinghaus [Allemagne] ; Martin Stanulla [Allemagne] ; Jéremie Rudant [France] ; Laurent Orsi [France] ; Jacqueline Clavel [France] ; Elizabeth Milne [Australie] ; Rodney J. Scott [Australie] ; Ching-Hon Pui [États-Unis] ; Nancy J. Cox [États-Unis] ; Mignon L. Loh [États-Unis] ; Jun J. Yang [États-Unis] ; Andrew D. Skol [États-Unis] ; Kenan Onel [États-Unis]Source :
- Nature Communications [ 2041-1723 ] ; 2016.
Abstract
Paediatric B-cell precursor acute lymphoblastic leukaemia (BCP-ALL) is the most common cancer of childhood, yet little is known about BCP-ALL predisposition. In this study, in 2,187 cases of European ancestry and 5,543 controls, we discover and replicate a locus indexed by rs77728904 at 9p21.3 associated with BCP-ALL susceptibility (
Url:
DOI: 10.1038/ncomms10635
PubMed: 26868379
PubMed Central: 4754340
Affiliations:
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PMC:4754340Le document en format XML
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in paediatric B-cell precursor acute lymphoblastic leukaemia aetiology</title>
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<author><name sortKey="Ellinghaus, Eva" sort="Ellinghaus, Eva" uniqKey="Ellinghaus E" first="Eva" last="Ellinghaus">Eva Ellinghaus</name>
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<author><name sortKey="Stanulla, Martin" sort="Stanulla, Martin" uniqKey="Stanulla M" first="Martin" last="Stanulla">Martin Stanulla</name>
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<author><name sortKey="Skol, Andrew D" sort="Skol, Andrew D" uniqKey="Skol A" first="Andrew D." last="Skol">Andrew D. Skol</name>
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<affiliation wicri:level="1"><nlm:aff id="a1"><institution>Department of Pediatrics, University of Chicago</institution>
, 900 East 57th Street, Room 5140, MC 4060, Chicago, Illinois 60637, USA</nlm:aff>
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<wicri:regionArea>, 900 East 57th Street, Room 5140, MC 4060, Chicago, Illinois 60637</wicri:regionArea>
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<sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">A variant at 9p21.3 functionally implicates <italic>CDKN2B</italic>
in paediatric B-cell precursor acute lymphoblastic leukaemia aetiology</title>
<author><name sortKey="Hungate, Eric A" sort="Hungate, Eric A" uniqKey="Hungate E" first="Eric A." last="Hungate">Eric A. Hungate</name>
<affiliation wicri:level="1"><nlm:aff id="a1"><institution>Department of Pediatrics, University of Chicago</institution>
, 900 East 57th Street, Room 5140, MC 4060, Chicago, Illinois 60637, USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>, 900 East 57th Street, Room 5140, MC 4060, Chicago, Illinois 60637</wicri:regionArea>
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</affiliation>
</author>
<author><name sortKey="Vora, Sapana R" sort="Vora, Sapana R" uniqKey="Vora S" first="Sapana R." last="Vora">Sapana R. Vora</name>
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<country xml:lang="fr">États-Unis</country>
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</affiliation>
</author>
<author><name sortKey="Gamazon, Eric R" sort="Gamazon, Eric R" uniqKey="Gamazon E" first="Eric R." last="Gamazon">Eric R. Gamazon</name>
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<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>, Nashville, Tennessee 37232</wicri:regionArea>
<wicri:noRegion>Tennessee 37232</wicri:noRegion>
</affiliation>
<affiliation wicri:level="1"><nlm:aff id="a4"><institution>The Academic Medical Center, University of Amsterdam</institution>
, Amsterdam 1105 AZ,<country>The Netherlands</country>
</nlm:aff>
<country xml:lang="fr">Pays-Bas</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
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<author><name sortKey="Moriyama, Takaya" sort="Moriyama, Takaya" uniqKey="Moriyama T" first="Takaya" last="Moriyama">Takaya Moriyama</name>
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<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>, Memphis, Tennessee 38105</wicri:regionArea>
<wicri:noRegion>Tennessee 38105</wicri:noRegion>
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<author><name sortKey="Best, Timothy" sort="Best, Timothy" uniqKey="Best T" first="Timothy" last="Best">Timothy Best</name>
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<author><name sortKey="Hulur, Imge" sort="Hulur, Imge" uniqKey="Hulur I" first="Imge" last="Hulur">Imge Hulur</name>
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<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>, Chicago, Illinois 60637</wicri:regionArea>
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<author><name sortKey="Lee, Younghee" sort="Lee, Younghee" uniqKey="Lee Y" first="Younghee" last="Lee">Younghee Lee</name>
<affiliation wicri:level="1"><nlm:aff id="a3"><institution>Department of Medicine, Vanderbilt University Medical Center</institution>
, Nashville, Tennessee 37232, USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>, Nashville, Tennessee 37232</wicri:regionArea>
<wicri:noRegion>Tennessee 37232</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Evans, Tiffany Jane" sort="Evans, Tiffany Jane" uniqKey="Evans T" first="Tiffany-Jane" last="Evans">Tiffany-Jane Evans</name>
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, New South Wales 2305,<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><name sortKey="Ellinghaus, Eva" sort="Ellinghaus, Eva" uniqKey="Ellinghaus E" first="Eva" last="Ellinghaus">Eva Ellinghaus</name>
<affiliation wicri:level="1"><nlm:aff id="a8"><institution>Institute of Clinical Molecular Biology, Christian-Albrechts University</institution>
, Kiel 24118,<country>Germany</country>
</nlm:aff>
<country xml:lang="fr">Allemagne</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Stanulla, Martin" sort="Stanulla, Martin" uniqKey="Stanulla M" first="Martin" last="Stanulla">Martin Stanulla</name>
<affiliation wicri:level="1"><nlm:aff id="a9"><institution>Department of Pediatrics, University Hospital Schleswig-Holstein</institution>
, Kiel 24105,<country>Germany</country>
</nlm:aff>
<country xml:lang="fr">Allemagne</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Rudant, Jeremie" sort="Rudant, Jeremie" uniqKey="Rudant J" first="Jéremie" last="Rudant">Jéremie Rudant</name>
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, Villejuif 94807,<country>France</country>
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<country xml:lang="fr">France</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
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<affiliation wicri:level="1"><nlm:aff id="a11"><institution>UMRS-1153, Epidemiology and Biostatistics Sorbonne Paris Cité Center (CRESS), Paris-Descartes University</institution>
, Paris 75270,<country>France</country>
</nlm:aff>
<country xml:lang="fr">France</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
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<author><name sortKey="Orsi, Laurent" sort="Orsi, Laurent" uniqKey="Orsi L" first="Laurent" last="Orsi">Laurent Orsi</name>
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, Villejuif 94807,<country>France</country>
</nlm:aff>
<country xml:lang="fr">France</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
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<affiliation wicri:level="1"><nlm:aff id="a11"><institution>UMRS-1153, Epidemiology and Biostatistics Sorbonne Paris Cité Center (CRESS), Paris-Descartes University</institution>
, Paris 75270,<country>France</country>
</nlm:aff>
<country xml:lang="fr">France</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
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<author><name sortKey="Clavel, Jacqueline" sort="Clavel, Jacqueline" uniqKey="Clavel J" first="Jacqueline" last="Clavel">Jacqueline Clavel</name>
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, Villejuif 94807,<country>France</country>
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<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
<affiliation wicri:level="1"><nlm:aff id="a11"><institution>UMRS-1153, Epidemiology and Biostatistics Sorbonne Paris Cité Center (CRESS), Paris-Descartes University</institution>
, Paris 75270,<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="a12"><institution>French National Registry of Childhood Hematopoietic Malignancies (RNHE)</institution>
, Villejuif 94807,<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="Milne, Elizabeth" sort="Milne, Elizabeth" uniqKey="Milne E" first="Elizabeth" last="Milne">Elizabeth Milne</name>
<affiliation wicri:level="1"><nlm:aff id="a13"><institution>Telethon Kids Institute, University of Western Australia</institution>
, Crawley, Western Australia 6872,<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="Scott, Rodney J" sort="Scott, Rodney J" uniqKey="Scott R" first="Rodney J." last="Scott">Rodney J. Scott</name>
<affiliation wicri:level="1"><nlm:aff id="a7"><institution>Faculty of Medicine and Health, Information Based Medicine, Hunter Medical Research Institute, School of Biomedical Sciences and Pharmacy, University of Newcastle, New Lambton</institution>
, New South Wales 2305,<country>Australia</country>
</nlm:aff>
<country xml:lang="fr">Australie</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
<affiliation wicri:level="1"><nlm:aff id="a14"><institution>Division of Molecular Medicine, Pathology North, John Hunter Hospital</institution>
, Newcastle, New South Wales 2305,<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="Pui, Ching Hon" sort="Pui, Ching Hon" uniqKey="Pui C" first="Ching-Hon" last="Pui">Ching-Hon Pui</name>
<affiliation wicri:level="1"><nlm:aff id="a15"><institution>Department of Oncology, St Jude Children's Research Hospital</institution>
, Memphis, Tennessee 38105, USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>, Memphis, Tennessee 38105</wicri:regionArea>
<wicri:noRegion>Tennessee 38105</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Cox, Nancy J" sort="Cox, Nancy J" uniqKey="Cox N" first="Nancy J." last="Cox">Nancy J. Cox</name>
<affiliation wicri:level="1"><nlm:aff id="a3"><institution>Department of Medicine, Vanderbilt University Medical Center</institution>
, Nashville, Tennessee 37232, USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>, Nashville, Tennessee 37232</wicri:regionArea>
<wicri:noRegion>Tennessee 37232</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Loh, Mignon L" sort="Loh, Mignon L" uniqKey="Loh M" first="Mignon L." last="Loh">Mignon L. Loh</name>
<affiliation wicri:level="1"><nlm:aff id="a16"><institution>Department of Pediatrics, University of California–San Francisco</institution>
, San Francisco, California 94143, USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>, San Francisco, California 94143</wicri:regionArea>
<wicri:noRegion>California 94143</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Yang, Jun J" sort="Yang, Jun J" uniqKey="Yang J" first="Jun J." last="Yang">Jun J. Yang</name>
<affiliation wicri:level="1"><nlm:aff id="a5"><institution>Department of Pharmaceutical Sciences, St Jude Children's Research Hospital</institution>
, Memphis, Tennessee 38105, USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>, Memphis, Tennessee 38105</wicri:regionArea>
<wicri:noRegion>Tennessee 38105</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Skol, Andrew D" sort="Skol, Andrew D" uniqKey="Skol A" first="Andrew D." last="Skol">Andrew D. Skol</name>
<affiliation wicri:level="1"><nlm:aff id="a1"><institution>Department of Pediatrics, University of Chicago</institution>
, 900 East 57th Street, Room 5140, MC 4060, Chicago, Illinois 60637, USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>, 900 East 57th Street, Room 5140, MC 4060, Chicago, Illinois 60637</wicri:regionArea>
<wicri:noRegion>Illinois 60637</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Onel, Kenan" sort="Onel, Kenan" uniqKey="Onel K" first="Kenan" last="Onel">Kenan Onel</name>
<affiliation wicri:level="1"><nlm:aff id="a1"><institution>Department of Pediatrics, University of Chicago</institution>
, 900 East 57th Street, Room 5140, MC 4060, Chicago, Illinois 60637, USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>, 900 East 57th Street, Room 5140, MC 4060, Chicago, Illinois 60637</wicri:regionArea>
<wicri:noRegion>Illinois 60637</wicri:noRegion>
</affiliation>
</author>
</analytic>
<series><title level="j">Nature Communications</title>
<idno type="eISSN">2041-1723</idno>
<imprint><date when="2016">2016</date>
</imprint>
</series>
</biblStruct>
</sourceDesc>
</fileDesc>
<profileDesc><textClass></textClass>
</profileDesc>
</teiHeader>
<front><div type="abstract" xml:lang="en"><p>Paediatric B-cell precursor acute lymphoblastic leukaemia (BCP-ALL) is the most common cancer of childhood, yet little is known about BCP-ALL predisposition. In this study, in 2,187 cases of European ancestry and 5,543 controls, we discover and replicate a locus indexed by rs77728904 at 9p21.3 associated with BCP-ALL susceptibility (<italic>P</italic>
<sub>combined</sub>
=3.32 × 10<sup>−15</sup>
, OR=1.72) and independent from rs3731217, the previously reported ALL-associated variant in this region. Of correlated SNPs tagged by this locus, only rs662463 is significant in African Americans, suggesting it is a plausible causative variant. Functional analysis shows that rs662463 is a <italic>cis</italic>
-eQTL for <italic>CDKN2B</italic>
, with the risk allele associated with lower expression, and suggests that rs662463 influences BCP-ALL risk by regulating <italic>CDKN2B</italic>
expression through CEBPB signalling. Functional analysis of rs3731217 suggests it is associated with BCP-ALL by acting within a splicing regulatory element determining <italic>CDKN2A</italic>
exon 3 usage (<italic>P</italic>
=0.01). These findings provide new insights into the critical role of the <italic>CDKN2</italic>
locus in BCP-ALL aetiology.</p>
</div>
</front>
<back><div1 type="bibliography"><listBibl><biblStruct><analytic><author><name sortKey="Mullighan, C G" uniqKey="Mullighan C">C. G. Mullighan</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Cazzaniga, G" uniqKey="Cazzaniga G">G. Cazzaniga</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Van Der Weyden, L" uniqKey="Van Der Weyden L">L. van der Weyden</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Enciso Mora, V" uniqKey="Enciso Mora V">V. Enciso-Mora</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Trevino, L R" uniqKey="Trevino L">L. R. Trevino</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Papaemmanuil, E" uniqKey="Papaemmanuil E">E. Papaemmanuil</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Xu, H" uniqKey="Xu H">H. Xu</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Sherborne, A L" uniqKey="Sherborne A">A. L. Sherborne</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Ellinghaus, E" uniqKey="Ellinghaus E">E. Ellinghaus</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Migliorini, G" uniqKey="Migliorini G">G. Migliorini</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Perez Andreu, V" uniqKey="Perez Andreu V">V. Perez-Andreu</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Orsi, L" uniqKey="Orsi L">L. Orsi</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Rudant, J" uniqKey="Rudant J">J. Rudant</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Borowitz, M J" uniqKey="Borowitz M">M. J. Borowitz</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Evans, T J" uniqKey="Evans T">T. J. Evans</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Akasaka, T" uniqKey="Akasaka T">T. Akasaka</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Mcvean, G A" uniqKey="Mcvean G">G. A. McVean</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Walsh, K M" uniqKey="Walsh K">K. M. Walsh</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Pasmant, E" uniqKey="Pasmant E">E. Pasmant</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Nicolae, D L" uniqKey="Nicolae D">D. L. Nicolae</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Trynka, G" uniqKey="Trynka G">G. Trynka</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Lonsdale, J" uniqKey="Lonsdale J">J. Lonsdale</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Battle, A" uniqKey="Battle A">A. Battle</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Ward, L D" uniqKey="Ward L">L. D. Ward</name>
</author>
<author><name sortKey="Kellis, M" uniqKey="Kellis M">M. Kellis</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Boyle, A P" uniqKey="Boyle A">A. P. Boyle</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Dunham, I" uniqKey="Dunham I">I. Dunham</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Wang, J" uniqKey="Wang J">J. Wang</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Matys, V" uniqKey="Matys V">V. Matys</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Lappalainen, T" uniqKey="Lappalainen T">T. Lappalainen</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Stranger, B E" uniqKey="Stranger B">B. E. Stranger</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Lee, Y" uniqKey="Lee Y">Y. Lee</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Quelle, D E" uniqKey="Quelle D">D. E. Quelle</name>
</author>
<author><name sortKey="Zindy, F" uniqKey="Zindy F">F. Zindy</name>
</author>
<author><name sortKey="Ashmun, R A" uniqKey="Ashmun R">R. A. Ashmun</name>
</author>
<author><name sortKey="Sherr, C J" uniqKey="Sherr C">C. J. Sherr</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Lin, Y C" uniqKey="Lin Y">Y. C. Lin</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Stott, F J" uniqKey="Stott F">F. J. Stott</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Tanguay, R L" uniqKey="Tanguay R">R. L. Tanguay</name>
</author>
<author><name sortKey="Gallie, D R" uniqKey="Gallie D">D. R. Gallie</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Stranks, G" uniqKey="Stranks G">G. Stranks</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Mullighan, C G" uniqKey="Mullighan C">C. G. Mullighan</name>
</author>
<author><name sortKey="Williams, R T" uniqKey="Williams R">R. T. Williams</name>
</author>
<author><name sortKey="Downing, J R" uniqKey="Downing J">J. R. Downing</name>
</author>
<author><name sortKey="Sherr, C J" uniqKey="Sherr C">C. J. Sherr</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Mullighan, C G" uniqKey="Mullighan C">C. G. Mullighan</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Ladomery, M" uniqKey="Ladomery M">M. Ladomery</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Zhang, J" uniqKey="Zhang J">J. Zhang</name>
</author>
<author><name sortKey="Manley, J L" uniqKey="Manley J">J. L. Manley</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Loo, J C" uniqKey="Loo J">J. C. Loo</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Harland, M" uniqKey="Harland M">M. Harland</name>
</author>
<author><name sortKey="Mistry, S" uniqKey="Mistry S">S. Mistry</name>
</author>
<author><name sortKey="Bishop, D T" uniqKey="Bishop D">D. T. Bishop</name>
</author>
<author><name sortKey="Bishop, J A" uniqKey="Bishop J">J. A. Bishop</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Winick, N" uniqKey="Winick N">N. Winick</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Manolio, T A" uniqKey="Manolio T">T. A. Manolio</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Korn, J M" uniqKey="Korn J">J. M. Korn</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Ehret, G B" uniqKey="Ehret G">G. B. Ehret</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Metayer, C" uniqKey="Metayer C">C. Metayer</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Krawczak, M" uniqKey="Krawczak M">M. Krawczak</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Purcell, S" uniqKey="Purcell S">S. Purcell</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Meyer, L R" uniqKey="Meyer L">L. R. Meyer</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Price, A L" uniqKey="Price A">A. L. Price</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Howie, B N" uniqKey="Howie B">B. N. Howie</name>
</author>
<author><name sortKey="Donnelly, P" uniqKey="Donnelly P">P. Donnelly</name>
</author>
<author><name sortKey="Marchini, J" uniqKey="Marchini J">J. Marchini</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Delaneau, O" uniqKey="Delaneau O">O. Delaneau</name>
</author>
<author><name sortKey="Marchini, J" uniqKey="Marchini J">J. Marchini</name>
</author>
<author><name sortKey="Zagury, J F" uniqKey="Zagury J">J. F. Zagury</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Marchini, J" uniqKey="Marchini J">J. Marchini</name>
</author>
<author><name sortKey="Howie, B" uniqKey="Howie B">B. Howie</name>
</author>
<author><name sortKey="Myers, S" uniqKey="Myers S">S. Myers</name>
</author>
<author><name sortKey="Mcvean, G" uniqKey="Mcvean G">G. McVean</name>
</author>
<author><name sortKey="Donnelly, P" uniqKey="Donnelly P">P. Donnelly</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Willer, C J" uniqKey="Willer C">C. J. Willer</name>
</author>
<author><name sortKey="Li, Y" uniqKey="Li Y">Y. Li</name>
</author>
<author><name sortKey="Abecasis, G R" uniqKey="Abecasis G">G. R. Abecasis</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Higgins, J P" uniqKey="Higgins J">J. P. Higgins</name>
</author>
<author><name sortKey="Thompson, S G" uniqKey="Thompson S">S. G. Thompson</name>
</author>
<author><name sortKey="Deeks, J J" uniqKey="Deeks J">J. J. Deeks</name>
</author>
<author><name sortKey="Altman, D G" uniqKey="Altman D">D. G. Altman</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Devlin, B" uniqKey="Devlin B">B. Devlin</name>
</author>
<author><name sortKey="Roeder, K" uniqKey="Roeder K">K. Roeder</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Pruim, R J" uniqKey="Pruim R">R. J. Pruim</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Barrett, J C" uniqKey="Barrett J">J. C. Barrett</name>
</author>
<author><name sortKey="Fry, B" uniqKey="Fry B">B. Fry</name>
</author>
<author><name sortKey="Maller, J" uniqKey="Maller J">J. Maller</name>
</author>
<author><name sortKey="Daly, M J" uniqKey="Daly M">M. J. Daly</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Bild, D E" uniqKey="Bild D">D. E. Bild</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Pritchard, J K" uniqKey="Pritchard J">J. K. Pritchard</name>
</author>
<author><name sortKey="Stephens, M" uniqKey="Stephens M">M. Stephens</name>
</author>
<author><name sortKey="Donnelly, P" uniqKey="Donnelly P">P. Donnelly</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Yang, J J" uniqKey="Yang J">J. J. Yang</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Mao, X" uniqKey="Mao X">X. Mao</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Zeller, T" uniqKey="Zeller T">T. Zeller</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Bernstein, B E" uniqKey="Bernstein B">B. E. Bernstein</name>
</author>
</analytic>
</biblStruct>
<biblStruct></biblStruct>
<biblStruct><analytic><author><name sortKey="Sandelin, A" uniqKey="Sandelin A">A. Sandelin</name>
</author>
<author><name sortKey="Alkema, W" uniqKey="Alkema W">W. Alkema</name>
</author>
<author><name sortKey="Engstrom, P" uniqKey="Engstrom P">P. Engstrom</name>
</author>
<author><name sortKey="Wasserman, W W" uniqKey="Wasserman W">W. W. Wasserman</name>
</author>
<author><name sortKey="Lenhard, B" uniqKey="Lenhard B">B. Lenhard</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Trapnell, C" uniqKey="Trapnell C">C. Trapnell</name>
</author>
</analytic>
</biblStruct>
<biblStruct></biblStruct>
<biblStruct><analytic><author><name sortKey="Thierry Mieg, D" uniqKey="Thierry Mieg D">D. Thierry-Mieg</name>
</author>
<author><name sortKey="Thierry Mieg, J" uniqKey="Thierry Mieg J">J. Thierry-Mieg</name>
</author>
</analytic>
</biblStruct>
</listBibl>
</div1>
</back>
</TEI>
<pmc article-type="research-article"><pmc-dir>properties open_access</pmc-dir>
<front><journal-meta><journal-id journal-id-type="nlm-ta">Nat Commun</journal-id>
<journal-id journal-id-type="iso-abbrev">Nat Commun</journal-id>
<journal-title-group><journal-title>Nature Communications</journal-title>
</journal-title-group>
<issn pub-type="epub">2041-1723</issn>
<publisher><publisher-name>Nature Publishing Group</publisher-name>
</publisher>
</journal-meta>
<article-meta><article-id pub-id-type="pmid">26868379</article-id>
<article-id pub-id-type="pmc">4754340</article-id>
<article-id pub-id-type="pii">ncomms10635</article-id>
<article-id pub-id-type="doi">10.1038/ncomms10635</article-id>
<article-categories><subj-group subj-group-type="heading"><subject>Article</subject>
</subj-group>
</article-categories>
<title-group><article-title>A variant at 9p21.3 functionally implicates <italic>CDKN2B</italic>
in paediatric B-cell precursor acute lymphoblastic leukaemia aetiology</article-title>
</title-group>
<contrib-group><contrib contrib-type="author"><name><surname>Hungate</surname>
<given-names>Eric A.</given-names>
</name>
<xref ref-type="aff" rid="a1">1</xref>
<xref ref-type="author-notes" rid="n1">*</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Vora</surname>
<given-names>Sapana R.</given-names>
</name>
<xref ref-type="aff" rid="a2">2</xref>
<xref ref-type="author-notes" rid="n1">*</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Gamazon</surname>
<given-names>Eric R.</given-names>
</name>
<xref ref-type="aff" rid="a3">3</xref>
<xref ref-type="aff" rid="a4">4</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Moriyama</surname>
<given-names>Takaya</given-names>
</name>
<xref ref-type="aff" rid="a5">5</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Best</surname>
<given-names>Timothy</given-names>
</name>
<xref ref-type="aff" rid="a2">2</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Hulur</surname>
<given-names>Imge</given-names>
</name>
<xref ref-type="aff" rid="a6">6</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Lee</surname>
<given-names>Younghee</given-names>
</name>
<xref ref-type="aff" rid="a3">3</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Evans</surname>
<given-names>Tiffany-Jane</given-names>
</name>
<xref ref-type="aff" rid="a7">7</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Ellinghaus</surname>
<given-names>Eva</given-names>
</name>
<xref ref-type="aff" rid="a8">8</xref>
<contrib-id contrib-id-type="orcid">http://orcid.org/0000-0003-2914-3382</contrib-id>
</contrib>
<contrib contrib-type="author"><name><surname>Stanulla</surname>
<given-names>Martin</given-names>
</name>
<xref ref-type="aff" rid="a9">9</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Rudant</surname>
<given-names>Jéremie</given-names>
</name>
<xref ref-type="aff" rid="a10">10</xref>
<xref ref-type="aff" rid="a11">11</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Orsi</surname>
<given-names>Laurent</given-names>
</name>
<xref ref-type="aff" rid="a10">10</xref>
<xref ref-type="aff" rid="a11">11</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Clavel</surname>
<given-names>Jacqueline</given-names>
</name>
<xref ref-type="aff" rid="a10">10</xref>
<xref ref-type="aff" rid="a11">11</xref>
<xref ref-type="aff" rid="a12">12</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Milne</surname>
<given-names>Elizabeth</given-names>
</name>
<xref ref-type="aff" rid="a13">13</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Scott</surname>
<given-names>Rodney J.</given-names>
</name>
<xref ref-type="aff" rid="a7">7</xref>
<xref ref-type="aff" rid="a14">14</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Pui</surname>
<given-names>Ching-Hon</given-names>
</name>
<xref ref-type="aff" rid="a15">15</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Cox</surname>
<given-names>Nancy J.</given-names>
</name>
<xref ref-type="aff" rid="a3">3</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Loh</surname>
<given-names>Mignon L.</given-names>
</name>
<xref ref-type="aff" rid="a16">16</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Yang</surname>
<given-names>Jun J.</given-names>
</name>
<xref ref-type="aff" rid="a5">5</xref>
<contrib-id contrib-id-type="orcid">http://orcid.org/0000-0002-0770-9659</contrib-id>
</contrib>
<contrib contrib-type="author"><name><surname>Skol</surname>
<given-names>Andrew D.</given-names>
</name>
<xref ref-type="aff" rid="a1">1</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Onel</surname>
<given-names>Kenan</given-names>
</name>
<xref ref-type="corresp" rid="c1">a</xref>
<xref ref-type="aff" rid="a1">1</xref>
</contrib>
<aff id="a1"><label>1</label>
<institution>Department of Pediatrics, University of Chicago</institution>
, 900 East 57th Street, Room 5140, MC 4060, Chicago, Illinois 60637, USA</aff>
<aff id="a2"><label>2</label>
<institution>Committee on Cancer Biology, University of Chicago</institution>
, Chicago, Illinois 60637, USA</aff>
<aff id="a3"><label>3</label>
<institution>Department of Medicine, Vanderbilt University Medical Center</institution>
, Nashville, Tennessee 37232, USA</aff>
<aff id="a4"><label>4</label>
<institution>The Academic Medical Center, University of Amsterdam</institution>
, Amsterdam 1105 AZ,<country>The Netherlands</country>
</aff>
<aff id="a5"><label>5</label>
<institution>Department of Pharmaceutical Sciences, St Jude Children's Research Hospital</institution>
, Memphis, Tennessee 38105, USA</aff>
<aff id="a6"><label>6</label>
<institution>Committee on Genetics, Genomics and Systems Biology, University of Chicago</institution>
, Chicago, Illinois 60637, USA</aff>
<aff id="a7"><label>7</label>
<institution>Faculty of Medicine and Health, Information Based Medicine, Hunter Medical Research Institute, School of Biomedical Sciences and Pharmacy, University of Newcastle, New Lambton</institution>
, New South Wales 2305,<country>Australia</country>
</aff>
<aff id="a8"><label>8</label>
<institution>Institute of Clinical Molecular Biology, Christian-Albrechts University</institution>
, Kiel 24118,<country>Germany</country>
</aff>
<aff id="a9"><label>9</label>
<institution>Department of Pediatrics, University Hospital Schleswig-Holstein</institution>
, Kiel 24105,<country>Germany</country>
</aff>
<aff id="a10"><label>10</label>
<institution>INSERM U1153 Epidemiology and Biostatistics Sorbonne Paris Cité Center (CRESS), Epidemiology of Childhood and Adolescent Cancers Team (EPICEA)</institution>
, Villejuif 94807,<country>France</country>
</aff>
<aff id="a11"><label>11</label>
<institution>UMRS-1153, Epidemiology and Biostatistics Sorbonne Paris Cité Center (CRESS), Paris-Descartes University</institution>
, Paris 75270,<country>France</country>
</aff>
<aff id="a12"><label>12</label>
<institution>French National Registry of Childhood Hematopoietic Malignancies (RNHE)</institution>
, Villejuif 94807,<country>France</country>
</aff>
<aff id="a13"><label>13</label>
<institution>Telethon Kids Institute, University of Western Australia</institution>
, Crawley, Western Australia 6872,<country>Australia</country>
</aff>
<aff id="a14"><label>14</label>
<institution>Division of Molecular Medicine, Pathology North, John Hunter Hospital</institution>
, Newcastle, New South Wales 2305,<country>Australia</country>
</aff>
<aff id="a15"><label>15</label>
<institution>Department of Oncology, St Jude Children's Research Hospital</institution>
, Memphis, Tennessee 38105, USA</aff>
<aff id="a16"><label>16</label>
<institution>Department of Pediatrics, University of California–San Francisco</institution>
, San Francisco, California 94143, USA</aff>
</contrib-group>
<author-notes><corresp id="c1"><label>a</label>
<email>konel@uchicago.edu</email>
</corresp>
<fn id="n1"><label>*</label>
<p>These authors contributed equally to this work.</p>
</fn>
</author-notes>
<pub-date pub-type="epub"><day>12</day>
<month>02</month>
<year>2016</year>
</pub-date>
<pub-date pub-type="collection"><year>2016</year>
</pub-date>
<volume>7</volume>
<elocation-id>10635</elocation-id>
<history><date date-type="received"><day>23</day>
<month>04</month>
<year>2015</year>
</date>
<date date-type="accepted"><day>07</day>
<month>01</month>
<year>2016</year>
</date>
</history>
<permissions><copyright-statement>Copyright © 2016, Nature Publishing Group, a division of Macmillan Publishers Limited. All Rights Reserved.</copyright-statement>
<copyright-year>2016</copyright-year>
<copyright-holder>Nature Publishing Group, a division of Macmillan Publishers Limited. All Rights Reserved.</copyright-holder>
<license license-type="open-access" xlink:href="http://creativecommons.org/licenses/by/4.0/"><pmc-comment>author-paid</pmc-comment>
<license-p>This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article's Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit <ext-link ext-link-type="uri" xlink:href="http://creativecommons.org/licenses/by/4.0/">http://creativecommons.org/licenses/by/4.0/</ext-link>
</license-p>
</license>
</permissions>
<abstract><p>Paediatric B-cell precursor acute lymphoblastic leukaemia (BCP-ALL) is the most common cancer of childhood, yet little is known about BCP-ALL predisposition. In this study, in 2,187 cases of European ancestry and 5,543 controls, we discover and replicate a locus indexed by rs77728904 at 9p21.3 associated with BCP-ALL susceptibility (<italic>P</italic>
<sub>combined</sub>
=3.32 × 10<sup>−15</sup>
, OR=1.72) and independent from rs3731217, the previously reported ALL-associated variant in this region. Of correlated SNPs tagged by this locus, only rs662463 is significant in African Americans, suggesting it is a plausible causative variant. Functional analysis shows that rs662463 is a <italic>cis</italic>
-eQTL for <italic>CDKN2B</italic>
, with the risk allele associated with lower expression, and suggests that rs662463 influences BCP-ALL risk by regulating <italic>CDKN2B</italic>
expression through CEBPB signalling. Functional analysis of rs3731217 suggests it is associated with BCP-ALL by acting within a splicing regulatory element determining <italic>CDKN2A</italic>
exon 3 usage (<italic>P</italic>
=0.01). These findings provide new insights into the critical role of the <italic>CDKN2</italic>
locus in BCP-ALL aetiology.</p>
</abstract>
<abstract abstract-type="web-summary"><p><inline-graphic id="i1" xlink:href="ncomms10635-i1.jpg"></inline-graphic>
A risk variant located at 9p21.3 is associated with cancer risk in pediatric B-cell precursor acute lymphoblastic leukaemia. Here, the authors show that this variant affects the gene expression of the tumour suppressor gene <italic>Cdkn2b</italic>
.</p>
</abstract>
</article-meta>
</front>
<floats-group><fig id="f1"><label>Figure 1</label>
<caption><title>Meta-analysis results for paediatric BCP-ALL.</title>
<p>(<bold>a</bold>
) Manhattan plot of associations for the discovery GWAS of 1,210 cases and 4,144 controls from four independent studies. The red line denotes the threshold for genome-wide significance. Peaks surpassing this threshold are found at the following: 7p12.2 (<italic>IKZF1</italic>
), 10q21.2 (<italic>ARID5B</italic>
) and 9p21.3 (<italic>CDKN2</italic>
). (<bold>b</bold>
) The top panel is the regional LocusZoom plot of the 9p21.3 locus extending 500 kb on either side of the index SNP, rs77728904 (shown in purple), and including all genotyped and imputed SNPs with MAF >0.01. The bottom panel is zoomed in (indicated by the solid black lines between plots) to include only the <italic>CDKN2</italic>
locus and surrounding recombination peaks. The <italic>r</italic>
<sup>2</sup>
(visualized by colour) demonstrates that rs77728904 and rs3731217 are in independent linkage blocks between the recombination peaks. <italic>r</italic>
<sup>2</sup>
for all SNPs in both panels is shown relative to rs77728904. (<bold>c</bold>
) Forest plot of OR with 95% confidence intervals (CIs) for rs77728904 in each of the studies comprising the discovery meta-analysis (Disc (Meta)), the full meta-analysis, the replication analysis and the combined analysis. Squares represent the OR; horizontal lines represent the CI; the solid vertical line represents OR=1; the blue dashed vertical line represents the OR in the combined discovery+replication sets.</p>
</caption>
<graphic xlink:href="ncomms10635-f1"></graphic>
</fig>
<fig id="f2"><label>Figure 2</label>
<caption><title>Haploview LD map of the 9p21.3 locus showing differences in the LD structure by ancestry in 1,000 Genomes Phase 1 populations.</title>
<p>LD is reported as <italic>r</italic>
<sup>2</sup>
with <italic>r</italic>
<sup>2</sup>
=0.01 white; 0.01<<italic>r</italic>
<sup>2</sup>
<1 shades of grey; <italic>r</italic>
<sup>2</sup>
=1 black. ASW, African American ancestry; CEU, European ancestry; MXL, Hispanic ancestry. rs77728904 is highlighted in orange and rs662463 is highlighted in blue.</p>
</caption>
<graphic xlink:href="ncomms10635-f2"></graphic>
</fig>
<fig id="f3"><label>Figure 3</label>
<caption><title>Multi-ethnic and functional analysis suggesting rs662463 is the causative BCP-ALL SNP tagged by the rs77728904-defined locus.</title>
<p>(<bold>a</bold>
) eQTL analysis from GTEx<xref ref-type="bibr" rid="b22">22</xref>
in whole blood showing the association of <italic>CDKN2B</italic>
expression with rs77728904 and rs662463 genotypes. For both SNPs, the minor allele is the risk allele. Each grey circle represents an individual. Each box plot shows the median rank normalized gene expression (black horizontal line), the first through third quartiles (purple box) and 1.5 × the interquartile range (whiskers). (<bold>b</bold>
) Motifs derived from ChIP data showing the effect of rs662463 on CEBPB binding. The genomic sequence (Ref) surrounding rs662463 is shown below the CEBPB-binding site motif logo for K562 cells from Factorbook<xref ref-type="bibr" rid="b27">27</xref>
, with the reference protective G-allele boxed and the risk A-allele in red. The CEBPB motif logo represents the position weight matrix (PWM) for each base. The PWM LOD scores calculated by HaploReg<xref ref-type="bibr" rid="b24">24</xref>
from TRANSFAC<xref ref-type="bibr" rid="b28">28</xref>
for two CEBPB-binding motifs (‘Tr1' or TRANSFAC accession M00912 and ‘Tr2' or TRANSFAC accession M00109) including either the protective or the risk allele of rs662463 demonstrate that the risk allele disrupts CEBPB binding. (<bold>c</bold>
) RNA-seq analysis in European ancestry LCLs<xref ref-type="bibr" rid="b29">29</xref>
, suggesting that the rs662463 genotype influences the correlation between <italic>CDKN2B</italic>
and <italic>CEBPB</italic>
expression, and that the rs662463 risk allele is associated with lower <italic>CDKN2B</italic>
expression. Shown are the best-fit lines overall (black line), for LCLs homozygous for the protective allele (blue line) and for LCLs with at least one copy (one copy: green circles and two copies: red circles) of the risk allele (green line). (<bold>d</bold>
) RNA-seq analysis in whole blood from an independent set of European ancestry individuals<xref ref-type="bibr" rid="b23">23</xref>
, demonstrating that the rs662463 genotype significantly influences the correlation between <italic>CDKN2B</italic>
and <italic>CEBPB</italic>
expression. The rs662463 risk allele attenuates this correlation and is associated with lower <italic>CDKN2B</italic>
expression. Shown are the best-fit lines overall (black line), for individuals homozygous for the protective allele (blue line) and for individuals with at least one copy (one copy: green circles and two copies: red circles) of the risk allele (green line).</p>
</caption>
<graphic xlink:href="ncomms10635-f3"></graphic>
</fig>
<fig id="f4"><label>Figure 4</label>
<caption><title>Functional analysis demonstrating rs3731217 is associated with <italic>CDKN2A</italic>
exon 3 usage.</title>
<p>(<bold>a</bold>
) Cartoon showing the major protein isoforms encoded by <italic>CDKN2A</italic>
: p14<sup>ARF</sup>
(blue arrows), p16γ (red arrows) and p16<sup>INK4a</sup>
(black arrow). The four main exons are labelled with exon 3 surrounded by a red box. rs3731217 is located in two overlapping intronic splicing elements between exon 1α and exon 1β. The image is modified from AceView<xref ref-type="bibr" rid="b70">70</xref>
. (<bold>b</bold>
) RNA-seq data from LCLs correlating exon usage with rs3731217 genotype showing that exon 3 usage is significantly associated with the protective G-allele (0, 1 and 2 on the <italic>x</italic>
axis refer to G-allele dosage). Each box plot shows the median rank normalized gene expression (black horizontal line), the first through third quartiles (box) and 1.5 × the interquartile range (whiskers).</p>
</caption>
<graphic xlink:href="ncomms10635-f4"></graphic>
</fig>
<table-wrap position="float" id="t1"><label>Table 1</label>
<caption><title>Association of SNPs in the 9p21.3 locus<xref ref-type="fn" rid="t1-fn3">*</xref>
with BCP-ALL in individuals of European ancestry.</title>
</caption>
<table frame="hsides" rules="groups" border="1"><colgroup><col align="left"></col>
<col align="center"></col>
<col align="center"></col>
<col align="center"></col>
<col align="center" char="("></col>
<col align="center"></col>
<col align="center"></col>
<col align="center"></col>
<col align="center"></col>
<col align="center"></col>
<col align="center"></col>
<col align="center"></col>
<col align="center"></col>
<col align="center"></col>
<col align="center"></col>
</colgroup>
<thead valign="bottom"><tr><th align="left" valign="top" charoff="50"><bold>SNP rsID</bold>
<xref ref-type="fn" rid="t1-fn4">†</xref>
</th>
<th align="center" valign="top" charoff="50"><bold>Position (bp)</bold>
<xref ref-type="fn" rid="t1-fn5">‡</xref>
</th>
<th align="center" valign="top" charoff="50"><bold>LD (</bold>
<italic><bold>r</bold>
</italic>
<sup><bold>2</bold>
</sup>
)<xref ref-type="fn" rid="t1-fn6">§</xref>
</th>
<th align="center" valign="top" charoff="50"><bold>Alleles</bold>
<xref ref-type="fn" rid="t1-fn7">‖</xref>
</th>
<th colspan="5" align="center" valign="top" char="(" charoff="50"><bold>Discovery meta-analysis (1,210 cases and 4,144 controls)</bold>
<hr></hr>
</th>
<th colspan="3" align="center" valign="top" charoff="50"><bold>Replication (977 cases and 1,399 controls)</bold>
<hr></hr>
</th>
<th colspan="3" align="center" valign="top" charoff="50"><bold>Combined</bold>
<hr></hr>
</th>
</tr>
<tr><th align="left" valign="top" charoff="50"> </th>
<th align="center" valign="top" charoff="50"> </th>
<th align="center" valign="top" charoff="50"> </th>
<th align="center" valign="top" charoff="50"> </th>
<th align="center" valign="top" char="(" charoff="50"><bold>OR (95% CI)</bold>
<xref ref-type="fn" rid="t1-fn3">*</xref>
</th>
<th colspan="2" align="center" valign="top" charoff="50"><italic><bold>P</bold>
</italic>
<bold>-value</bold>
<hr></hr>
</th>
<th align="center" valign="top" charoff="50"><italic><bold>P</bold>
</italic>
<sub><bold>het</bold>
</sub>
<xref ref-type="fn" rid="t1-fn8">¶</xref>
</th>
<th align="center" valign="top" charoff="50"><italic><bold>I</bold>
</italic>
<sup><bold>2</bold>
</sup>
<bold>(%)</bold>
<xref ref-type="fn" rid="t1-fn9">#</xref>
</th>
<th align="center" valign="top" charoff="50"><bold>OR (95% CI)</bold>
<xref ref-type="fn" rid="t1-fn3">*</xref>
</th>
<th colspan="2" align="center" valign="top" charoff="50"><italic><bold>P</bold>
</italic>
<bold>-value</bold>
<hr></hr>
</th>
<th align="center" valign="top" charoff="50"><bold>OR (95% CI)</bold>
<xref ref-type="fn" rid="t1-fn3">*</xref>
</th>
<th colspan="2" align="center" valign="top" charoff="50"><italic><bold>P</bold>
</italic>
<bold>-value</bold>
<hr></hr>
</th>
</tr>
<tr><th align="left" valign="top" charoff="50"> </th>
<th align="center" valign="top" charoff="50"> </th>
<th align="center" valign="top" charoff="50"> </th>
<th align="center" valign="top" charoff="50"> </th>
<th align="center" valign="top" char="(" charoff="50"> </th>
<th align="center" valign="top" charoff="50"><bold>Unconditional</bold>
<xref ref-type="fn" rid="t1-fn10">**</xref>
</th>
<th align="center" valign="top" charoff="50"><bold>Conditional</bold>
<xref ref-type="fn" rid="t1-fn11">††</xref>
</th>
<th align="center" valign="top" charoff="50"> </th>
<th align="center" valign="top" charoff="50"> </th>
<th align="center" valign="top" charoff="50"> </th>
<th align="center" valign="top" charoff="50"><bold>Unconditional</bold>
<xref ref-type="fn" rid="t1-fn10">**</xref>
</th>
<th align="center" valign="top" charoff="50"><bold>Conditional</bold>
<xref ref-type="fn" rid="t1-fn11">††</xref>
</th>
<th align="center" valign="top" charoff="50"> </th>
<th align="center" valign="top" charoff="50"><bold>Unconditional</bold>
<xref ref-type="fn" rid="t1-fn10">**</xref>
</th>
<th align="center" valign="top" charoff="50"><bold>Conditional</bold>
<xref ref-type="fn" rid="t1-fn11">††</xref>
</th>
</tr>
</thead>
<tbody valign="top"><tr><td align="left" valign="top" charoff="50">rs78545330</td>
<td align="center" valign="top" charoff="50">21,995,941</td>
<td align="center" valign="top" charoff="50">0.77</td>
<td align="center" valign="top" charoff="50">A/T</td>
<td align="center" valign="top" char="(" charoff="50">1.58 (1.34–1.86)</td>
<td align="center" valign="top" charoff="50">6.04 × 10<sup>−8</sup>
</td>
<td align="center" valign="top" charoff="50">1.06 × 10<sup>−6</sup>
</td>
<td align="center" valign="top" charoff="50">0.480</td>
<td align="center" valign="top" charoff="50">0</td>
<td align="center" valign="top" charoff="50">1.57 (1.31–1.89)</td>
<td align="center" valign="top" charoff="50">1.19 × 10<sup>−6</sup>
</td>
<td align="center" valign="top" charoff="50">1.84 × 10<sup>−5</sup>
</td>
<td align="center" valign="top" charoff="50">1.58 (1.39–1.78)</td>
<td align="center" valign="top" charoff="50">3.44 × 10<sup>−13</sup>
</td>
<td align="center" valign="top" charoff="50">8.37 × 10<sup>−11</sup>
</td>
</tr>
<tr><td align="left" valign="top" charoff="50">rs2811712</td>
<td align="center" valign="top" charoff="50">21,998,035</td>
<td align="center" valign="top" charoff="50">0.69</td>
<td align="center" valign="top" charoff="50">G/A</td>
<td align="center" valign="top" char="(" charoff="50">1.43 (1.22–1.68)</td>
<td align="center" valign="top" charoff="50">8.91 × 10<sup>−6</sup>
</td>
<td align="center" valign="top" charoff="50">1.09 × 10<sup>−4</sup>
</td>
<td align="center" valign="top" charoff="50">0.202</td>
<td align="center" valign="top" charoff="50">37.5</td>
<td align="center" valign="top" charoff="50">1.52 (1.34–1.69)</td>
<td align="center" valign="top" charoff="50">3.89 × 10<sup>−6</sup>
</td>
<td align="center" valign="top" charoff="50">7.60 × 10<sup>−5</sup>
</td>
<td align="center" valign="top" charoff="50">1.47 (1.31–1.65)</td>
<td align="center" valign="top" charoff="50">1.66 × 10<sup>−10</sup>
</td>
<td align="center" valign="top" charoff="50">3.40 × 10<sup>−8</sup>
</td>
</tr>
<tr><td align="left" valign="top" charoff="50">rs3218018</td>
<td align="center" valign="top" charoff="50">21,998,139</td>
<td align="center" valign="top" charoff="50">0.79</td>
<td align="center" valign="top" charoff="50">G/T</td>
<td align="center" valign="top" char="(" charoff="50">1.59 (1.34–1.88)</td>
<td align="center" valign="top" charoff="50">9.39 × 10<sup>−8</sup>
</td>
<td align="center" valign="top" charoff="50">1.42 × 0<sup>−6</sup>
</td>
<td align="center" valign="top" charoff="50">0.548</td>
<td align="center" valign="top" charoff="50">0</td>
<td align="center" valign="top" charoff="50">1.58 (1.31–1.91)</td>
<td align="center" valign="top" charoff="50">1.74 × 10<sup>−6</sup>
</td>
<td align="center" valign="top" charoff="50">4.76 × 10<sup>−5</sup>
</td>
<td align="center" valign="top" charoff="50">1.59 (1.40–1.80)</td>
<td align="center" valign="top" charoff="50">7.68 × 10<sup>−13</sup>
</td>
<td align="center" valign="top" charoff="50">2.85 × 10<sup>−10</sup>
</td>
</tr>
<tr><td align="left" valign="top" charoff="50">rs3218007</td>
<td align="center" valign="top" charoff="50">21,999,800</td>
<td align="center" valign="top" charoff="50">0.77</td>
<td align="center" valign="top" charoff="50">T/C</td>
<td align="center" valign="top" char="(" charoff="50">1.57 (1.33–1.84)</td>
<td align="center" valign="top" charoff="50">9.04 × 10<sup>−8</sup>
</td>
<td align="center" valign="top" charoff="50">1.49 × 10<sup>−6</sup>
</td>
<td align="center" valign="top" charoff="50">0.498</td>
<td align="center" valign="top" charoff="50">0</td>
<td align="center" valign="top" charoff="50">1.57 (1.31–1.88)</td>
<td align="center" valign="top" charoff="50">1.37 × 10<sup>−6</sup>
</td>
<td align="center" valign="top" charoff="50">2.23 × 10<sup>−5</sup>
</td>
<td align="center" valign="top" charoff="50">1.57 (1.39–1.77)</td>
<td align="center" valign="top" charoff="50">5.86 × 10<sup>−13</sup>
</td>
<td align="center" valign="top" charoff="50">1.42 × 10<sup>−10</sup>
</td>
</tr>
<tr><td align="left" valign="top" charoff="50">rs3218005</td>
<td align="center" valign="top" charoff="50">22,000,247</td>
<td align="center" valign="top" charoff="50">0.77</td>
<td align="center" valign="top" charoff="50">C/T</td>
<td align="center" valign="top" char="(" charoff="50">1.57 (1.33–1.84)</td>
<td align="center" valign="top" charoff="50">9.05 × 10<sup>−8</sup>
</td>
<td align="center" valign="top" charoff="50">1.50 × 10<sup>−6</sup>
</td>
<td align="center" valign="top" charoff="50">0.498</td>
<td align="center" valign="top" charoff="50">0</td>
<td align="center" valign="top" charoff="50">1.57 (1.31–1.88)</td>
<td align="center" valign="top" charoff="50">1.37 × 10<sup>−6</sup>
</td>
<td align="center" valign="top" charoff="50">2.23 × 10<sup>−5</sup>
</td>
<td align="center" valign="top" charoff="50">1.57 (1.39–1.77)</td>
<td align="center" valign="top" charoff="50">5.87 × 10<sup>−13</sup>
</td>
<td align="center" valign="top" charoff="50">1.42 × 10<sup>−10</sup>
</td>
</tr>
<tr><td align="left" valign="top" charoff="50">rs3218002</td>
<td align="center" valign="top" charoff="50">22,000,841</td>
<td align="center" valign="top" charoff="50">0.77</td>
<td align="center" valign="top" charoff="50">A/G</td>
<td align="center" valign="top" char="(" charoff="50">1.57 (1.33–1.85)</td>
<td align="center" valign="top" charoff="50">8.65 × 10<sup>−8</sup>
</td>
<td align="center" valign="top" charoff="50">1.45 × 10<sup>−6</sup>
</td>
<td align="center" valign="top" charoff="50">0.491</td>
<td align="center" valign="top" charoff="50">0</td>
<td align="center" valign="top" charoff="50">1.57 (1.31–1.88)</td>
<td align="center" valign="top" charoff="50">1.37 × 10<sup>−6</sup>
</td>
<td align="center" valign="top" charoff="50">2.23 × 10<sup>−5</sup>
</td>
<td align="center" valign="top" charoff="50">1.57 (1.39–1.77)</td>
<td align="center" valign="top" charoff="50">5.62 × 10<sup>−13</sup>
</td>
<td align="center" valign="top" charoff="50">1.38 × 10<sup>−10</sup>
</td>
</tr>
<tr><td align="left" valign="top" charoff="50">rs2069426</td>
<td align="center" valign="top" charoff="50">22,006,273</td>
<td align="center" valign="top" charoff="50">0.79</td>
<td align="center" valign="top" charoff="50">T/G</td>
<td align="center" valign="top" char="(" charoff="50">1.59 (1.34–1.88)</td>
<td align="center" valign="top" charoff="50">9.47 × 10<sup>−8</sup>
</td>
<td align="center" valign="top" charoff="50">1.42 × 10<sup>−6</sup>
</td>
<td align="center" valign="top" charoff="50">0.545</td>
<td align="center" valign="top" charoff="50">0</td>
<td align="center" valign="top" charoff="50">1.58 (1.31–1.90)</td>
<td align="center" valign="top" charoff="50">2.23 × 10<sup>−6</sup>
</td>
<td align="center" valign="top" charoff="50">5.85 × 10<sup>−5</sup>
</td>
<td align="center" valign="top" charoff="50">1.58 (1.39–1.80)</td>
<td align="center" valign="top" charoff="50">9.93 × 10<sup>−13</sup>
</td>
<td align="center" valign="top" charoff="50">3.52 × 10<sup>−10</sup>
</td>
</tr>
<tr><td align="left" valign="top" charoff="50">rs974336</td>
<td align="center" valign="top" charoff="50">22,006,348</td>
<td align="center" valign="top" charoff="50">0.77</td>
<td align="center" valign="top" charoff="50">T/C</td>
<td align="center" valign="top" char="(" charoff="50">1.57 (1.33–1.85)</td>
<td align="center" valign="top" charoff="50">7.67 × 10<sup>−8</sup>
</td>
<td align="center" valign="top" charoff="50">1.25 × 10<sup>−6</sup>
</td>
<td align="center" valign="top" charoff="50">0.514</td>
<td align="center" valign="top" charoff="50">0</td>
<td align="center" valign="top" charoff="50">1.60 (1.33–1.92)</td>
<td align="center" valign="top" charoff="50">4.18 × 10<sup>−7</sup>
</td>
<td align="center" valign="top" charoff="50">7.52 × 10<sup>−6</sup>
</td>
<td align="center" valign="top" charoff="50">1.58 (1.40–1.79)</td>
<td align="center" valign="top" charoff="50">1.58 × 10<sup>−13</sup>
</td>
<td align="center" valign="top" charoff="50">4.17 × 10<sup>−11</sup>
</td>
</tr>
<tr><td align="left" valign="top" charoff="50">rs2069422</td>
<td align="center" valign="top" charoff="50">22,008,026</td>
<td align="center" valign="top" charoff="50">0.70</td>
<td align="center" valign="top" charoff="50">G/T</td>
<td align="center" valign="top" char="(" charoff="50">1.44 (1.22–1.69)</td>
<td align="center" valign="top" charoff="50">1.33 × 10<sup>−5</sup>
</td>
<td align="center" valign="top" charoff="50">1.45 × 10<sup>−4</sup>
</td>
<td align="center" valign="top" charoff="50">0.240</td>
<td align="center" valign="top" charoff="50">30.0</td>
<td align="center" valign="top" charoff="50">1.52 (1.33–1.70)</td>
<td align="center" valign="top" charoff="50">6.53 × 10<sup>−6</sup>
</td>
<td align="center" valign="top" charoff="50">1.91 × 10<sup>−4</sup>
</td>
<td align="center" valign="top" charoff="50">1.47 (1.30–1.66)</td>
<td align="center" valign="top" charoff="50">4.02 × 10<sup>−10</sup>
</td>
<td align="center" valign="top" charoff="50">1.05 × 10<sup>−7</sup>
</td>
</tr>
<tr><td align="left" valign="top" charoff="50">rs77920300</td>
<td align="center" valign="top" charoff="50">22,012,441</td>
<td align="center" valign="top" charoff="50">0.79</td>
<td align="center" valign="top" charoff="50">T/C</td>
<td align="center" valign="top" char="(" charoff="50">1.60 (1.35–1.89)</td>
<td align="center" valign="top" charoff="50">4.26 × 10<sup>−8</sup>
</td>
<td align="center" valign="top" charoff="50">6.50 × 10<sup>−7</sup>
</td>
<td align="center" valign="top" charoff="50">0.583</td>
<td align="center" valign="top" charoff="50">0</td>
<td align="center" valign="top" charoff="50">1.57 (1.30–1.89)</td>
<td align="center" valign="top" charoff="50">2.43 × 10<sup>−6</sup>
</td>
<td align="center" valign="top" charoff="50">6.26 × 10<sup>−5</sup>
</td>
<td align="center" valign="top" charoff="50">1.59 (1.40–1.80)</td>
<td align="center" valign="top" charoff="50">4.95 × 10<sup>−13</sup>
</td>
<td align="center" valign="top" charoff="50">1.78 × 10<sup>−10</sup>
</td>
</tr>
<tr><td align="left" valign="top" charoff="50">rs116729641</td>
<td align="center" valign="top" charoff="50">22,025,432</td>
<td align="center" valign="top" charoff="50">0.79</td>
<td align="center" valign="top" charoff="50">A/G</td>
<td align="center" valign="top" char="(" charoff="50">1.61 (1.36–1.90)</td>
<td align="center" valign="top" charoff="50">2.84 × 10<sup>−8</sup>
</td>
<td align="center" valign="top" charoff="50">4.49 × 10<sup>−7</sup>
</td>
<td align="center" valign="top" charoff="50">0.614</td>
<td align="center" valign="top" charoff="50">0</td>
<td align="center" valign="top" charoff="50">1.57 (1.30–1.89)</td>
<td align="center" valign="top" charoff="50">2.31 × 10<sup>−6</sup>
</td>
<td align="center" valign="top" charoff="50">5.83 × 10<sup>−5</sup>
</td>
<td align="center" valign="top" charoff="50">1.59 (1.40–1.80)</td>
<td align="center" valign="top" charoff="50">3.16 × 10<sup>−13</sup>
</td>
<td align="center" valign="top" charoff="50">1.17 × 10<sup>−10</sup>
</td>
</tr>
<tr><td align="left" valign="top" charoff="50">rs77284052</td>
<td align="center" valign="top" charoff="50">22,025,885</td>
<td align="center" valign="top" charoff="50">0.79</td>
<td align="center" valign="top" charoff="50">T/C</td>
<td align="center" valign="top" char="(" charoff="50">1.61 (1.36–1.90)</td>
<td align="center" valign="top" charoff="50">2.82 × 10<sup>−8</sup>
</td>
<td align="center" valign="top" charoff="50">4.46 × 10<sup>−7</sup>
</td>
<td align="center" valign="top" charoff="50">0.618</td>
<td align="center" valign="top" charoff="50">0</td>
<td align="center" valign="top" charoff="50">1.57 (1.30–1.89)</td>
<td align="center" valign="top" charoff="50">2.31 × 10<sup>−6</sup>
</td>
<td align="center" valign="top" charoff="50">5.83 × 10<sup>−5</sup>
</td>
<td align="center" valign="top" charoff="50">1.59 (1.40–1.80)</td>
<td align="center" valign="top" charoff="50">3.14 × 10<sup>−13</sup>
</td>
<td align="center" valign="top" charoff="50">1.16 × 10<sup>−10</sup>
</td>
</tr>
<tr><td align="left" valign="top" charoff="50">rs598664</td>
<td align="center" valign="top" charoff="50">22,027,551</td>
<td align="center" valign="top" charoff="50">0.70</td>
<td align="center" valign="top" charoff="50">C/T</td>
<td align="center" valign="top" char="(" charoff="50">1.46 (1.25–1.72)</td>
<td align="center" valign="top" charoff="50">3.46 × 10<sup>−6</sup>
</td>
<td align="center" valign="top" charoff="50">4.19 × 10<sup>−5</sup>
</td>
<td align="center" valign="top" charoff="50">0.287</td>
<td align="center" valign="top" charoff="50">19.9</td>
<td align="center" valign="top" charoff="50">1.51 (1.26–1.81)</td>
<td align="center" valign="top" charoff="50">7.91 × 10<sup>−6</sup>
</td>
<td align="center" valign="top" charoff="50">2.21 × 10<sup>−4</sup>
</td>
<td align="center" valign="top" charoff="50">1.48 (1.32–1.67)</td>
<td align="center" valign="top" charoff="50">1.21 × 10<sup>−10</sup>
</td>
<td align="center" valign="top" charoff="50">3.47 × 10<sup>−8</sup>
</td>
</tr>
<tr><td align="left" valign="top" charoff="50">rs662463</td>
<td align="center" valign="top" charoff="50">22,030,438</td>
<td align="center" valign="top" charoff="50">0.70</td>
<td align="center" valign="top" charoff="50">A/G</td>
<td align="center" valign="top" char="(" charoff="50">1.46 (1.24–1.71)</td>
<td align="center" valign="top" charoff="50">3.71 × 10<sup>−6</sup>
</td>
<td align="center" valign="top" charoff="50">4.43 × 10<sup>−5</sup>
</td>
<td align="center" valign="top" charoff="50">0.288</td>
<td align="center" valign="top" charoff="50">19.7</td>
<td align="center" valign="top" charoff="50">1.50 (1.25–1.79)</td>
<td align="center" valign="top" charoff="50">1.16 × 10<sup>−5</sup>
</td>
<td align="center" valign="top" charoff="50">3.03 × 10<sup>−4</sup>
</td>
<td align="center" valign="top" charoff="50">1.48 (1.31–1.66)</td>
<td align="center" valign="top" charoff="50">1.87 × 10<sup>−10</sup>
</td>
<td align="center" valign="top" charoff="50">4.97 × 10<sup>−8</sup>
</td>
</tr>
<tr><td align="left" valign="top" charoff="50">rs79985856</td>
<td align="center" valign="top" charoff="50">22,033,824</td>
<td align="center" valign="top" charoff="50">0.79</td>
<td align="center" valign="top" charoff="50">T/C</td>
<td align="center" valign="top" char="(" charoff="50">1.61 (1.37–1.91)</td>
<td align="center" valign="top" charoff="50">2.03 × 10<sup>−8</sup>
</td>
<td align="center" valign="top" charoff="50">3.29 × 10<sup>−7</sup>
</td>
<td align="center" valign="top" charoff="50">0.657</td>
<td align="center" valign="top" charoff="50">0</td>
<td align="center" valign="top" charoff="50">1.56 (1.30–1.89)</td>
<td align="center" valign="top" charoff="50">2.86 × 10<sup>−6</sup>
</td>
<td align="center" valign="top" charoff="50">7.22 × 10<sup>−5</sup>
</td>
<td align="center" valign="top" charoff="50">1.59 (1.41–1.80)</td>
<td align="center" valign="top" charoff="50">2.84 × 10<sup>−13</sup>
</td>
<td align="center" valign="top" charoff="50">1.08 × 10<sup>−10</sup>
</td>
</tr>
<tr><td align="left" valign="top" charoff="50">rs79182326</td>
<td align="center" valign="top" charoff="50">22,034,267</td>
<td align="center" valign="top" charoff="50">0.69</td>
<td align="center" valign="top" charoff="50">T/C</td>
<td align="center" valign="top" char="(" charoff="50">1.45 (1.24–1.70)</td>
<td align="center" valign="top" charoff="50">4.30 × 10<sup>−6</sup>
</td>
<td align="center" valign="top" charoff="50">5.47 × 10<sup>−5</sup>
</td>
<td align="center" valign="top" charoff="50">0.303</td>
<td align="center" valign="top" charoff="50">16.3</td>
<td align="center" valign="top" charoff="50">1.45 (1.21–1.73)</td>
<td align="center" valign="top" charoff="50">4.72 × 10<sup>−5</sup>
</td>
<td align="center" valign="top" charoff="50">1.00 × 10<sup>−3</sup>
</td>
<td align="center" valign="top" charoff="50">1.45 (1.29–1.63)</td>
<td align="center" valign="top" charoff="50">8.33 × 10<sup>−10</sup>
</td>
<td align="center" valign="top" charoff="50">1.96 × 10<sup>−7</sup>
</td>
</tr>
<tr><td align="left" valign="top" charoff="50">rs76213463</td>
<td align="center" valign="top" charoff="50">22,040,839</td>
<td align="center" valign="top" charoff="50">0.79</td>
<td align="center" valign="top" charoff="50">A/G</td>
<td align="center" valign="top" char="(" charoff="50">1.62 (1.37–1.91)</td>
<td align="center" valign="top" charoff="50">1.68 × 10<sup>−8</sup>
</td>
<td align="center" valign="top" charoff="50">2.76 × 10<sup>−7</sup>
</td>
<td align="center" valign="top" charoff="50">0.636</td>
<td align="center" valign="top" charoff="50">0</td>
<td align="center" valign="top" charoff="50">1.56 (1.29–1.88)</td>
<td align="center" valign="top" charoff="50">3.70 × 10<sup>−6</sup>
</td>
<td align="center" valign="top" charoff="50">8.62 × 10<sup>−5</sup>
</td>
<td align="center" valign="top" charoff="50">1.59 (1.40–1.80)</td>
<td align="center" valign="top" charoff="50">3.08 × 10<sup>−13</sup>
</td>
<td align="center" valign="top" charoff="50">1.11 × 10<sup>−10</sup>
</td>
</tr>
<tr><td align="left" valign="top" charoff="50">rs80166549</td>
<td align="center" valign="top" charoff="50">22,041,155</td>
<td align="center" valign="top" charoff="50">0.79</td>
<td align="center" valign="top" charoff="50">G/A</td>
<td align="center" valign="top" char="(" charoff="50">1.62 (1.37–1.91)</td>
<td align="center" valign="top" charoff="50">1.67 × 10<sup>−8</sup>
</td>
<td align="center" valign="top" charoff="50">2.74 × 10<sup>−7</sup>
</td>
<td align="center" valign="top" charoff="50">0.635</td>
<td align="center" valign="top" charoff="50">0</td>
<td align="center" valign="top" charoff="50">1.56 (1.29–1.88)</td>
<td align="center" valign="top" charoff="50">3.70 × 10<sup>−6</sup>
</td>
<td align="center" valign="top" charoff="50">8.62 × 10<sup>−5</sup>
</td>
<td align="center" valign="top" charoff="50">1.59 (1.40–1.80)</td>
<td align="center" valign="top" charoff="50">3.06 × 10<sup>−13</sup>
</td>
<td align="center" valign="top" charoff="50">1.10 × 10<sup>−10</sup>
</td>
</tr>
<tr><td align="left" valign="top" charoff="50">rs1333035</td>
<td align="center" valign="top" charoff="50">22,044,059</td>
<td align="center" valign="top" charoff="50">0.69</td>
<td align="center" valign="top" charoff="50">G/A</td>
<td align="center" valign="top" char="(" charoff="50">1.46 (1.25–1.71)</td>
<td align="center" valign="top" charoff="50">1.78 × 10<sup>−6</sup>
</td>
<td align="center" valign="top" charoff="50">2.50 × 10<sup>−5</sup>
</td>
<td align="center" valign="top" charoff="50">0.238</td>
<td align="center" valign="top" charoff="50">30.2</td>
<td align="center" valign="top" charoff="50">1.50 (1.26–1.78)</td>
<td align="center" valign="top" charoff="50">6.87 × 10<sup>−6</sup>
</td>
<td align="center" valign="top" charoff="50">1.42 × 10<sup>−4</sup>
</td>
<td align="center" valign="top" charoff="50">1.48 (1.31–1.66)</td>
<td align="center" valign="top" charoff="50">5.45 × 10<sup>−11</sup>
</td>
<td align="center" valign="top" charoff="50">1.36 × 10<sup>−8</sup>
</td>
</tr>
<tr><td align="left" valign="top" charoff="50">rs1333034</td>
<td align="center" valign="top" charoff="50">22,044,122</td>
<td align="center" valign="top" charoff="50">0.70</td>
<td align="center" valign="top" charoff="50">C/T</td>
<td align="center" valign="top" char="(" charoff="50">1.47 (1.25–1.72)</td>
<td align="center" valign="top" charoff="50">2.93 × 10<sup>−6</sup>
</td>
<td align="center" valign="top" charoff="50">3.58 × 10<sup>−5</sup>
</td>
<td align="center" valign="top" charoff="50">0.307</td>
<td align="center" valign="top" charoff="50">15.3</td>
<td align="center" valign="top" charoff="50">1.50 (1.26–1.80)</td>
<td align="center" valign="top" charoff="50">9.04 × 10<sup>−6</sup>
</td>
<td align="center" valign="top" charoff="50">2.34 × 10<sup>−4</sup>
</td>
<td align="center" valign="top" charoff="50">1.48 (1.32–1.67)</td>
<td align="center" valign="top" charoff="50">1.17 × 10<sup>−10</sup>
</td>
<td align="center" valign="top" charoff="50">3.14 × 10<sup>−8</sup>
</td>
</tr>
<tr><td align="left" valign="top" charoff="50">rs17694555</td>
<td align="center" valign="top" charoff="50">22,051,295</td>
<td align="center" valign="top" charoff="50">0.78</td>
<td align="center" valign="top" charoff="50">G/A</td>
<td align="center" valign="top" char="(" charoff="50">1.61 (1.35–1.92)</td>
<td align="center" valign="top" charoff="50">1.61 × 10<sup>−7</sup>
</td>
<td align="center" valign="top" charoff="50">2.24 × 10<sup>−6</sup>
</td>
<td align="center" valign="top" charoff="50">0.458</td>
<td align="center" valign="top" charoff="50">0</td>
<td align="center" valign="top" charoff="50">1.59 (1.40–1.78)</td>
<td align="center" valign="top" charoff="50">1.85 × 10<sup>−6</sup>
</td>
<td align="center" valign="top" charoff="50">4.28 × 10<sup>−5</sup>
</td>
<td align="center" valign="top" charoff="50">1.60 (1.41–1.82)</td>
<td align="center" valign="top" charoff="50">1.40 × 10<sup>−12</sup>
</td>
<td align="center" valign="top" charoff="50">4.08 × 10<sup>−10</sup>
</td>
</tr>
<tr><td align="left" valign="top" charoff="50">rs17756311</td>
<td align="center" valign="top" charoff="50">22,053,895</td>
<td align="center" valign="top" charoff="50">0.77</td>
<td align="center" valign="top" charoff="50">A/G</td>
<td align="center" valign="top" char="(" charoff="50">1.63 (1.37–1.94)</td>
<td align="center" valign="top" charoff="50">3.95 × 10<sup>−8</sup>
</td>
<td align="center" valign="top" charoff="50">7.00 × 10<sup>−7</sup>
</td>
<td align="center" valign="top" charoff="50">0.531</td>
<td align="center" valign="top" charoff="50">0</td>
<td align="center" valign="top" charoff="50">1.57 (1.30–1.90)</td>
<td align="center" valign="top" charoff="50">2.92 × 10<sup>−6</sup>
</td>
<td align="center" valign="top" charoff="50">5.74 × 10<sup>−5</sup>
</td>
<td align="center" valign="top" charoff="50">1.60 (1.41–1.82)</td>
<td align="center" valign="top" charoff="50">5.66 × 10<sup>−13</sup>
</td>
<td align="center" valign="top" charoff="50">1.81 × 10<sup>−10</sup>
</td>
</tr>
<tr><td align="left" valign="top" charoff="50">rs74655961</td>
<td align="center" valign="top" charoff="50">22,054,164</td>
<td align="center" valign="top" charoff="50">0.77</td>
<td align="center" valign="top" charoff="50">G/A</td>
<td align="center" valign="top" char="(" charoff="50">1.64 (1.38–1.95)</td>
<td align="center" valign="top" charoff="50">2.90 × 10<sup>−8</sup>
</td>
<td align="center" valign="top" charoff="50">5.16 × 10<sup>−7</sup>
</td>
<td align="center" valign="top" charoff="50">0.557</td>
<td align="center" valign="top" charoff="50">0</td>
<td align="center" valign="top" charoff="50">1.55 (1.28–1.87)</td>
<td align="center" valign="top" charoff="50">5.85 × 10<sup>−6</sup>
</td>
<td align="center" valign="top" charoff="50">1.11 × 10<sup>−4</sup>
</td>
<td align="center" valign="top" charoff="50">1.60 (1.40–1.82)</td>
<td align="center" valign="top" charoff="50">8.63 × 10<sup>−13</sup>
</td>
<td align="center" valign="top" charoff="50">2.71 × 10<sup>−10</sup>
</td>
</tr>
<tr><td align="left" valign="top" charoff="50">rs17694572</td>
<td align="center" valign="top" charoff="50">22,054,356</td>
<td align="center" valign="top" charoff="50">0.77</td>
<td align="center" valign="top" charoff="50">A/G</td>
<td align="center" valign="top" char="(" charoff="50">1.63 (1.37–1.94)</td>
<td align="center" valign="top" charoff="50">2.89 × 10<sup>−8</sup>
</td>
<td align="center" valign="top" charoff="50">4.98 × 10<sup>−7</sup>
</td>
<td align="center" valign="top" charoff="50">0.526</td>
<td align="center" valign="top" charoff="50">0</td>
<td align="center" valign="top" charoff="50">1.54 (1.28–1.87)</td>
<td align="center" valign="top" charoff="50">6.87 × 10<sup>−6</sup>
</td>
<td align="center" valign="top" charoff="50">1.28 × 10<sup>−4</sup>
</td>
<td align="center" valign="top" charoff="50">1.59 (1.40–1.81)</td>
<td align="center" valign="top" charoff="50">1.01 × 10<sup>−12</sup>
</td>
<td align="center" valign="top" charoff="50">3.02 × 10<sup>−10</sup>
</td>
</tr>
<tr><td align="left" valign="top" charoff="50">rs77728904</td>
<td align="center" valign="top" charoff="50">22,057,530</td>
<td align="center" valign="top" charoff="50">—</td>
<td align="center" valign="top" charoff="50">C/A</td>
<td align="center" valign="top" char="(" charoff="50">1.71 (1.42–2.05)</td>
<td align="center" valign="top" charoff="50">1.02 × 10<sup>−8</sup>
</td>
<td align="center" valign="top" charoff="50">1.25 × 10<sup>−7</sup>
</td>
<td align="center" valign="top" charoff="50">0.687</td>
<td align="center" valign="top" charoff="50">0</td>
<td align="center" valign="top" charoff="50">1.74 (1.42–2.12)</td>
<td align="center" valign="top" charoff="50">6.28 × 10<sup>−8</sup>
</td>
<td align="center" valign="top" charoff="50">1.59 × 10<sup>−6</sup>
</td>
<td align="center" valign="top" charoff="50">1.72 (1.50–1.97)</td>
<td align="center" valign="top" charoff="50">3.32 × 10<sup>−15</sup>
</td>
<td align="center" valign="top" charoff="50">9.34 × 10<sup>−13</sup>
</td>
</tr>
<tr><td align="left" valign="top" charoff="50">rs115574830</td>
<td align="center" valign="top" charoff="50">22,059,061</td>
<td align="center" valign="top" charoff="50">0.87</td>
<td align="center" valign="top" charoff="50">A/T</td>
<td align="center" valign="top" char="(" charoff="50">1.61 (1.35–1.92)</td>
<td align="center" valign="top" charoff="50">7.09 × 10<sup>−8</sup>
</td>
<td align="center" valign="top" charoff="50">8.60 × 10<sup>−7</sup>
</td>
<td align="center" valign="top" charoff="50">0.574</td>
<td align="center" valign="top" charoff="50">0</td>
<td align="center" valign="top" charoff="50">1.55 (1.28–1.88)</td>
<td align="center" valign="top" charoff="50">8.34 × 10<sup>−6</sup>
</td>
<td align="center" valign="top" charoff="50">1.38 × 10<sup>−4</sup>
</td>
<td align="center" valign="top" charoff="50">1.58 (1.39–1.80)</td>
<td align="center" valign="top" charoff="50">2.83 × 10<sup>−12</sup>
</td>
<td align="center" valign="top" charoff="50">5.32 × 10<sup>−10</sup>
</td>
</tr>
</tbody>
</table>
<table-wrap-foot><fn id="t1-fn1"><p>AA, African American; BCP-ALL, B-cell precursor acute lymphoblastic leukaemia; CI, confidence interval; GWAS, genome-wide association study; LD, linkage disequilibrium; OR, odds ratio; SNP, single-nucleotide polymorphism.</p>
</fn>
<fn id="t1-fn2"><p>Highlighted are SNPs with the smallest <italic>P</italic>
-values for each part of the analysis (rs77728904 in blue for the discovery GWAS, the replication analysis and the combined analysis; rs662463 in green for AA in the multi-ethnic analysis).</p>
</fn>
<fn id="t1-fn3"><p><sup>*</sup>
OR with 95% CI.</p>
</fn>
<fn id="t1-fn4"><p><sup>†</sup>
SNPs in LD (<italic>r</italic>
<sup>2</sup>
<sub>EUR</sub>
>0.60 in 1,000 Genomes Phase 1 (ref. <xref ref-type="bibr" rid="b17">17</xref>
) from HaploReg<xref ref-type="bibr" rid="b24">24</xref>
) with rs77728904 (rs115939893 and rs72654280 were not included, because they were not present in the replication and multi-ethnic analyses; all SNPs in <italic>r</italic>
<sup>2</sup>
<sub>EUR</sub>
>0.2 are listed in <xref ref-type="supplementary-material" rid="S1">Supplementary Table 4</xref>
).</p>
</fn>
<fn id="t1-fn5"><p><sup>‡</sup>
Physical positions on chromosome 9 are from NCBI build 37/hg19.</p>
</fn>
<fn id="t1-fn6"><p><sup>§</sup>
LD (<italic>r</italic>
<sup>2</sup>
) with the index SNP (rs77728904).</p>
</fn>
<fn id="t1-fn7"><p><sup>‖</sup>
Minor/major allele.</p>
</fn>
<fn id="t1-fn8"><p><sup>¶</sup>
Cochran's test of heterogeneity in the studies comprising the discovery meta-analysis.</p>
</fn>
<fn id="t1-fn9"><p><sup>#</sup>
Percentage of variation in the meta-analysis due to heterogeneity.</p>
</fn>
<fn id="t1-fn10"><p><sup>**</sup>
Unconditional <italic>P</italic>
-values for listed SNPs.</p>
</fn>
<fn id="t1-fn11"><p><sup>††</sup>
<italic>P</italic>
values for listed SNPs when conditioned on rs3731217.</p>
</fn>
</table-wrap-foot>
</table-wrap>
<table-wrap position="float" id="t2"><label>Table 2</label>
<caption><title>Association of SNPs in the 9p21.3 locus<xref ref-type="fn" rid="t2-fn3">*</xref>
with BCP-ALL in HAs and AAs.</title>
</caption>
<table frame="hsides" rules="groups" border="1"><colgroup><col align="left"></col>
<col align="center"></col>
<col align="center"></col>
<col align="center"></col>
<col align="center"></col>
<col align="center"></col>
<col align="center"></col>
<col align="center"></col>
<col align="center"></col>
<col align="center"></col>
<col align="center"></col>
</colgroup>
<thead valign="bottom"><tr><th align="left" valign="top" charoff="50"><bold>SNP (rsID)</bold>
</th>
<th align="center" valign="top" charoff="50"><bold>Position (bp)</bold>
<xref ref-type="fn" rid="t2-fn4">†</xref>
</th>
<th colspan="3" align="center" valign="top" charoff="50"><bold>LD (</bold>
<italic><bold>r</bold>
</italic>
<sup><bold>2</bold>
</sup>
<bold>) by population</bold>
<xref ref-type="fn" rid="t2-fn3">*</xref>
<hr></hr>
</th>
<th colspan="3" align="center" valign="top" charoff="50"><bold>HA (NA>10% and NA>YRI</bold>
)<xref ref-type="fn" rid="t2-fn5">‡</xref>
<bold>(391 cases and 1,008 controls)</bold>
<hr></hr>
</th>
<th colspan="3" align="center" valign="top" charoff="50"><bold>AA (YRI>70%)</bold>
<xref ref-type="fn" rid="t2-fn6">§</xref>
<bold>(203 cases and 1,363 controls)</bold>
<hr></hr>
</th>
</tr>
<tr><th align="left" valign="top" charoff="50"> </th>
<th align="center" valign="top" charoff="50"> </th>
<th align="center" valign="top" charoff="50"><bold>EUR</bold>
<xref ref-type="fn" rid="t2-fn7">‖</xref>
</th>
<th align="center" valign="top" charoff="50"><bold>MXL</bold>
<xref ref-type="fn" rid="t2-fn8">¶</xref>
</th>
<th align="center" valign="top" charoff="50"><bold>ASW</bold>
<xref ref-type="fn" rid="t2-fn9">#</xref>
</th>
<th align="center" valign="top" charoff="50"><bold>OR (95% CI)</bold>
<xref ref-type="fn" rid="t2-fn10">**</xref>
</th>
<th colspan="2" align="center" valign="top" charoff="50"><italic><bold>P</bold>
</italic>
<sub><bold>HA</bold>
</sub>
<bold>value</bold>
<hr></hr>
</th>
<th align="center" valign="top" charoff="50"><bold>OR (95% CI)</bold>
<xref ref-type="fn" rid="t2-fn10">**</xref>
</th>
<th colspan="2" align="center" valign="top" charoff="50"><italic><bold>P</bold>
</italic>
<sub><bold>AA</bold>
</sub>
<bold>value</bold>
<hr></hr>
</th>
</tr>
<tr><th align="left" valign="top" charoff="50"> </th>
<th align="center" valign="top" charoff="50"> </th>
<th align="center" valign="top" charoff="50"> </th>
<th align="center" valign="top" charoff="50"> </th>
<th align="center" valign="top" charoff="50"> </th>
<th align="center" valign="top" charoff="50"> </th>
<th align="center" valign="top" charoff="50"><bold>Unconditional</bold>
<xref ref-type="fn" rid="t2-fn11">††</xref>
</th>
<th align="center" valign="top" charoff="50"><bold>Conditional</bold>
<xref ref-type="fn" rid="t2-fn12">‡‡</xref>
</th>
<th align="center" valign="top" charoff="50"> </th>
<th align="center" valign="top" charoff="50"><bold>Unconditional</bold>
<xref ref-type="fn" rid="t2-fn11">††</xref>
</th>
<th align="center" valign="top" charoff="50"><bold>Conditional</bold>
<xref ref-type="fn" rid="t2-fn12">‡‡</xref>
</th>
</tr>
</thead>
<tbody valign="top"><tr><td align="left" valign="top" charoff="50">rs78545330</td>
<td align="center" valign="top" charoff="50">21,995,941</td>
<td align="center" valign="top" charoff="50">0.77</td>
<td align="center" valign="top" charoff="50">0.83</td>
<td align="center" valign="top" charoff="50">0.28</td>
<td align="center" valign="top" charoff="50">1.51 (1.09–2.09)</td>
<td align="center" valign="top" charoff="50">0.014</td>
<td align="center" valign="top" charoff="50">0.014</td>
<td align="center" valign="top" charoff="50">1.18 (0.92–1.50)</td>
<td align="center" valign="top" charoff="50">0.185</td>
<td align="center" valign="top" charoff="50">0.255</td>
</tr>
<tr><td align="left" valign="top" charoff="50">rs2811712</td>
<td align="center" valign="top" charoff="50">21,998,035</td>
<td align="center" valign="top" charoff="50">0.69</td>
<td align="center" valign="top" charoff="50">0.83</td>
<td align="center" valign="top" charoff="50">0.28</td>
<td align="center" valign="top" charoff="50">1.48 (1.16–1.80)</td>
<td align="center" valign="top" charoff="50">0.017</td>
<td align="center" valign="top" charoff="50">0.018</td>
<td align="center" valign="top" charoff="50">1.15 (0.90–1.40)</td>
<td align="center" valign="top" charoff="50">0.276</td>
<td align="center" valign="top" charoff="50">0.329</td>
</tr>
<tr><td align="left" valign="top" charoff="50">rs3218018</td>
<td align="center" valign="top" charoff="50">21,998,139</td>
<td align="center" valign="top" charoff="50">0.79</td>
<td align="center" valign="top" charoff="50">0.83</td>
<td align="center" valign="top" charoff="50">0.86</td>
<td align="center" valign="top" charoff="50">1.54 (1.08–2.20)</td>
<td align="center" valign="top" charoff="50">0.017</td>
<td align="center" valign="top" charoff="50">0.030</td>
<td align="center" valign="top" charoff="50">1.13 (0.79–1.60)</td>
<td align="center" valign="top" charoff="50">0.512</td>
<td align="center" valign="top" charoff="50">0.404</td>
</tr>
<tr><td align="left" valign="top" charoff="50">rs3218007</td>
<td align="center" valign="top" charoff="50">21,999,800</td>
<td align="center" valign="top" charoff="50">0.77</td>
<td align="center" valign="top" charoff="50">0.83</td>
<td align="center" valign="top" charoff="50">0.28</td>
<td align="center" valign="top" charoff="50">1.47 (1.06–2.03)</td>
<td align="center" valign="top" charoff="50">0.021</td>
<td align="center" valign="top" charoff="50">0.023</td>
<td align="center" valign="top" charoff="50">1.14 (0.89–1.46)</td>
<td align="center" valign="top" charoff="50">0.288</td>
<td align="center" valign="top" charoff="50">0.347</td>
</tr>
<tr><td align="left" valign="top" charoff="50">rs3218005</td>
<td align="center" valign="top" charoff="50">22,000,247</td>
<td align="center" valign="top" charoff="50">0.77</td>
<td align="center" valign="top" charoff="50">0.83</td>
<td align="center" valign="top" charoff="50">0.28</td>
<td align="center" valign="top" charoff="50">1.51 (1.09–2.09)</td>
<td align="center" valign="top" charoff="50">0.014</td>
<td align="center" valign="top" charoff="50">0.014</td>
<td align="center" valign="top" charoff="50">1.14 (0.89–1.47)</td>
<td align="center" valign="top" charoff="50">0.285</td>
<td align="center" valign="top" charoff="50">0.342</td>
</tr>
<tr><td align="left" valign="top" charoff="50">rs3218002</td>
<td align="center" valign="top" charoff="50">22,000,841</td>
<td align="center" valign="top" charoff="50">0.77</td>
<td align="center" valign="top" charoff="50">0.83</td>
<td align="center" valign="top" charoff="50">0.28</td>
<td align="center" valign="top" charoff="50">1.49 (1.08–2.06)</td>
<td align="center" valign="top" charoff="50">0.016</td>
<td align="center" valign="top" charoff="50">0.014</td>
<td align="center" valign="top" charoff="50">1.15 (0.90–1.48)</td>
<td align="center" valign="top" charoff="50">0.253</td>
<td align="center" valign="top" charoff="50">0.315</td>
</tr>
<tr><td align="left" valign="top" charoff="50">rs2069426</td>
<td align="center" valign="top" charoff="50">22,006,273</td>
<td align="center" valign="top" charoff="50">0.79</td>
<td align="center" valign="top" charoff="50">0.83</td>
<td align="center" valign="top" charoff="50">0.86</td>
<td align="center" valign="top" charoff="50">1.51 (1.06–2.16)</td>
<td align="center" valign="top" charoff="50">0.024</td>
<td align="center" valign="top" charoff="50">0.035</td>
<td align="center" valign="top" charoff="50">1.16 (0.82–1.64)</td>
<td align="center" valign="top" charoff="50">0.409</td>
<td align="center" valign="top" charoff="50">0.333</td>
</tr>
<tr><td align="left" valign="top" charoff="50">rs974336</td>
<td align="center" valign="top" charoff="50">22,006,348</td>
<td align="center" valign="top" charoff="50">0.77</td>
<td align="center" valign="top" charoff="50">0.83</td>
<td align="center" valign="top" charoff="50">0.30</td>
<td align="center" valign="top" charoff="50">1.48 (1.07–2.05)</td>
<td align="center" valign="top" charoff="50">0.017</td>
<td align="center" valign="top" charoff="50">0.014</td>
<td align="center" valign="top" charoff="50">1.11 (0.87–1.42)</td>
<td align="center" valign="top" charoff="50">0.391</td>
<td align="center" valign="top" charoff="50">0.477</td>
</tr>
<tr><td align="left" valign="top" charoff="50">rs2069422</td>
<td align="center" valign="top" charoff="50">22,008,026</td>
<td align="center" valign="top" charoff="50">0.70</td>
<td align="center" valign="top" charoff="50">0.83</td>
<td align="center" valign="top" charoff="50">0.86</td>
<td align="center" valign="top" charoff="50">1.47 (1.12–1.82)</td>
<td align="center" valign="top" charoff="50">0.028</td>
<td align="center" valign="top" charoff="50">0.042</td>
<td align="center" valign="top" charoff="50">1.28 (0.92–1.64)</td>
<td align="center" valign="top" charoff="50">0.179</td>
<td align="center" valign="top" charoff="50">0.157</td>
</tr>
<tr><td align="left" valign="top" charoff="50">rs77920300</td>
<td align="center" valign="top" charoff="50">22,012,441</td>
<td align="center" valign="top" charoff="50">0.79</td>
<td align="center" valign="top" charoff="50">0.83</td>
<td align="center" valign="top" charoff="50">0.93</td>
<td align="center" valign="top" charoff="50">1.50 (1.05–2.14)</td>
<td align="center" valign="top" charoff="50">0.025</td>
<td align="center" valign="top" charoff="50">0.036</td>
<td align="center" valign="top" charoff="50">1.12 (0.79–1.58)</td>
<td align="center" valign="top" charoff="50">0.529</td>
<td align="center" valign="top" charoff="50">0.401</td>
</tr>
<tr><td align="left" valign="top" charoff="50">rs116729641</td>
<td align="center" valign="top" charoff="50">22,025,432</td>
<td align="center" valign="top" charoff="50">0.79</td>
<td align="center" valign="top" charoff="50">0.83</td>
<td align="center" valign="top" charoff="50">0.86</td>
<td align="center" valign="top" charoff="50">1.48 (1.04–2.12)</td>
<td align="center" valign="top" charoff="50">0.029</td>
<td align="center" valign="top" charoff="50">0.043</td>
<td align="center" valign="top" charoff="50">1.12 (0.79–1.58)</td>
<td align="center" valign="top" charoff="50">0.537</td>
<td align="center" valign="top" charoff="50">0.409</td>
</tr>
<tr><td align="left" valign="top" charoff="50">rs77284052</td>
<td align="center" valign="top" charoff="50">22,025,885</td>
<td align="center" valign="top" charoff="50">0.79</td>
<td align="center" valign="top" charoff="50">0.83</td>
<td align="center" valign="top" charoff="50">0.93</td>
<td align="center" valign="top" charoff="50">1.48 (1.04–2.12)</td>
<td align="center" valign="top" charoff="50">0.029</td>
<td align="center" valign="top" charoff="50">0.043</td>
<td align="center" valign="top" charoff="50">1.12 (0.79–1.58)</td>
<td align="center" valign="top" charoff="50">0.533</td>
<td align="center" valign="top" charoff="50">0.406</td>
</tr>
<tr><td align="left" valign="top" charoff="50">rs598664</td>
<td align="center" valign="top" charoff="50">22,027,551</td>
<td align="center" valign="top" charoff="50">0.70</td>
<td align="center" valign="top" charoff="50">0.83</td>
<td align="center" valign="top" charoff="50">0.93</td>
<td align="center" valign="top" charoff="50">1.44 (1.02–2.05)</td>
<td align="center" valign="top" charoff="50">0.038</td>
<td align="center" valign="top" charoff="50">0.057</td>
<td align="center" valign="top" charoff="50">1.10 (0.78–1.56)</td>
<td align="center" valign="top" charoff="50">0.580</td>
<td align="center" valign="top" charoff="50">0.437</td>
</tr>
<tr><td align="left" valign="top" charoff="50">rs662463</td>
<td align="center" valign="top" charoff="50">22,030,438</td>
<td align="center" valign="top" charoff="50">0.70</td>
<td align="center" valign="top" charoff="50">0.83</td>
<td align="center" valign="top" charoff="50">0.58</td>
<td align="center" valign="top" charoff="50">1.45 (1.03–2.06)</td>
<td align="center" valign="top" charoff="50">0.034</td>
<td align="center" valign="top" charoff="50">0.051</td>
<td align="center" valign="top" charoff="50"><bold>1.55</bold>
(<bold>1.16–2.06)</bold>
</td>
<td align="center" valign="top" charoff="50"><bold>0.003</bold>
</td>
<td align="center" valign="top" charoff="50"><bold>0.002</bold>
</td>
</tr>
<tr><td align="left" valign="top" charoff="50">rs79985856</td>
<td align="center" valign="top" charoff="50">22,033,824</td>
<td align="center" valign="top" charoff="50">0.79</td>
<td align="center" valign="top" charoff="50">0.83</td>
<td align="center" valign="top" charoff="50">0.93</td>
<td align="center" valign="top" charoff="50">1.50 (1.05–2.14)</td>
<td align="center" valign="top" charoff="50">0.026</td>
<td align="center" valign="top" charoff="50">0.039</td>
<td align="center" valign="top" charoff="50">1.14 (0.81–1.62)</td>
<td align="center" valign="top" charoff="50">0.450</td>
<td align="center" valign="top" charoff="50">0.332</td>
</tr>
<tr><td align="left" valign="top" charoff="50">rs79182326</td>
<td align="center" valign="top" charoff="50">22,034,267</td>
<td align="center" valign="top" charoff="50">0.69</td>
<td align="center" valign="top" charoff="50">0.70</td>
<td align="center" valign="top" charoff="50">0.93</td>
<td align="center" valign="top" charoff="50">1.41 (1.00–2.00)</td>
<td align="center" valign="top" charoff="50">0.049</td>
<td align="center" valign="top" charoff="50">0.073</td>
<td align="center" valign="top" charoff="50">1.15 (0.81–1.63)</td>
<td align="center" valign="top" charoff="50">0.425</td>
<td align="center" valign="top" charoff="50">0.297</td>
</tr>
<tr><td align="left" valign="top" charoff="50">rs76213463</td>
<td align="center" valign="top" charoff="50">22,040,839</td>
<td align="center" valign="top" charoff="50">0.79</td>
<td align="center" valign="top" charoff="50">0.83</td>
<td align="center" valign="top" charoff="50">0.93</td>
<td align="center" valign="top" charoff="50">1.50 (1.05–2.15)</td>
<td align="center" valign="top" charoff="50">0.025</td>
<td align="center" valign="top" charoff="50">0.036</td>
<td align="center" valign="top" charoff="50">1.17 (0.83–1.63)</td>
<td align="center" valign="top" charoff="50">0.364</td>
<td align="center" valign="top" charoff="50">0.292</td>
</tr>
<tr><td align="left" valign="top" charoff="50">rs80166549</td>
<td align="center" valign="top" charoff="50">22,041,155</td>
<td align="center" valign="top" charoff="50">0.79</td>
<td align="center" valign="top" charoff="50">0.83</td>
<td align="center" valign="top" charoff="50">0.93</td>
<td align="center" valign="top" charoff="50">1.51 (1.05–2.15)</td>
<td align="center" valign="top" charoff="50">0.024</td>
<td align="center" valign="top" charoff="50">0.035</td>
<td align="center" valign="top" charoff="50">1.14 (0.81–1.59)</td>
<td align="center" valign="top" charoff="50">0.454</td>
<td align="center" valign="top" charoff="50">0.379</td>
</tr>
<tr><td align="left" valign="top" charoff="50">rs1333035</td>
<td align="center" valign="top" charoff="50">22,044,059</td>
<td align="center" valign="top" charoff="50">0.69</td>
<td align="center" valign="top" charoff="50">0.83</td>
<td align="center" valign="top" charoff="50">0.32</td>
<td align="center" valign="top" charoff="50">1.41 (1.02–1.94)</td>
<td align="center" valign="top" charoff="50">0.037</td>
<td align="center" valign="top" charoff="50">0.032</td>
<td align="center" valign="top" charoff="50">1.10 (0.87–1.41)</td>
<td align="center" valign="top" charoff="50">0.427</td>
<td align="center" valign="top" charoff="50">0.505</td>
</tr>
<tr><td align="left" valign="top" charoff="50">rs1333034</td>
<td align="center" valign="top" charoff="50">22,044,122</td>
<td align="center" valign="top" charoff="50">0.70</td>
<td align="center" valign="top" charoff="50">0.83</td>
<td align="center" valign="top" charoff="50">0.93</td>
<td align="center" valign="top" charoff="50">1.48 (1.05–2.10)</td>
<td align="center" valign="top" charoff="50">0.026</td>
<td align="center" valign="top" charoff="50">0.039</td>
<td align="center" valign="top" charoff="50">1.12 (0.80–1.57)</td>
<td align="center" valign="top" charoff="50">0.500</td>
<td align="center" valign="top" charoff="50">0.413</td>
</tr>
<tr><td align="left" valign="top" charoff="50">rs17694555</td>
<td align="center" valign="top" charoff="50">22,051,295</td>
<td align="center" valign="top" charoff="50">0.78</td>
<td align="center" valign="top" charoff="50">0.83</td>
<td align="center" valign="top" charoff="50">0.11</td>
<td align="center" valign="top" charoff="50">1.71 (1.31–2.11)</td>
<td align="center" valign="top" charoff="50">0.008</td>
<td align="center" valign="top" charoff="50">0.015</td>
<td align="center" valign="top" charoff="50">1.79 (0.33–3.25)</td>
<td align="center" valign="top" charoff="50">0.430</td>
<td align="center" valign="top" charoff="50">0.386</td>
</tr>
<tr><td align="left" valign="top" charoff="50">rs17756311</td>
<td align="center" valign="top" charoff="50">22,053,895</td>
<td align="center" valign="top" charoff="50">0.77</td>
<td align="center" valign="top" charoff="50">0.83</td>
<td align="center" valign="top" charoff="50">1</td>
<td align="center" valign="top" charoff="50">1.43 (0.99–2.05)</td>
<td align="center" valign="top" charoff="50">0.055</td>
<td align="center" valign="top" charoff="50">0.076</td>
<td align="center" valign="top" charoff="50">1.05 (0.75–1.49)</td>
<td align="center" valign="top" charoff="50">0.766</td>
<td align="center" valign="top" charoff="50">0.665</td>
</tr>
<tr><td align="left" valign="top" charoff="50">rs74655961</td>
<td align="center" valign="top" charoff="50">22054164</td>
<td align="center" valign="top" charoff="50">0.77</td>
<td align="center" valign="top" charoff="50">0.83</td>
<td align="center" valign="top" charoff="50">1</td>
<td align="center" valign="top" charoff="50">1.46 (1.01–2.10)</td>
<td align="center" valign="top" charoff="50">0.041</td>
<td align="center" valign="top" charoff="50">0.058</td>
<td align="center" valign="top" charoff="50">1.14 (0.82–1.60)</td>
<td align="center" valign="top" charoff="50">0.430</td>
<td align="center" valign="top" charoff="50">0.355</td>
</tr>
<tr><td align="left" valign="top" charoff="50">rs17694572</td>
<td align="center" valign="top" charoff="50">22,054,356</td>
<td align="center" valign="top" charoff="50">0.77</td>
<td align="center" valign="top" charoff="50">0.83</td>
<td align="center" valign="top" charoff="50">1</td>
<td align="center" valign="top" charoff="50">1.46 (1.02–2.10)</td>
<td align="center" valign="top" charoff="50">0.041</td>
<td align="center" valign="top" charoff="50">0.058</td>
<td align="center" valign="top" charoff="50">1.11 (0.80–1.56)</td>
<td align="center" valign="top" charoff="50">0.528</td>
<td align="center" valign="top" charoff="50">0.445</td>
</tr>
<tr><td align="left" valign="top" charoff="50">rs77728904</td>
<td align="center" valign="top" charoff="50">22,057,530</td>
<td align="center" valign="top" charoff="50">—</td>
<td align="center" valign="top" charoff="50">—</td>
<td align="center" valign="top" charoff="50">—</td>
<td align="center" valign="top" charoff="50">1.76 (1.21–2.57)</td>
<td align="center" valign="top" charoff="50">0.003</td>
<td align="center" valign="top" charoff="50">0.005</td>
<td align="center" valign="top" charoff="50">1.16 (0.82–1.64)</td>
<td align="center" valign="top" charoff="50">0.403</td>
<td align="center" valign="top" charoff="50">0.281</td>
</tr>
<tr><td align="left" valign="top" charoff="50">rs115574830</td>
<td align="center" valign="top" charoff="50">22,059,061</td>
<td align="center" valign="top" charoff="50">0.87</td>
<td align="center" valign="top" charoff="50">1</td>
<td align="center" valign="top" charoff="50">1</td>
<td align="center" valign="top" charoff="50">1.70 (1.17–2.48)</td>
<td align="center" valign="top" charoff="50">0.005</td>
<td align="center" valign="top" charoff="50">0.007</td>
<td align="center" valign="top" charoff="50">1.26 (0.90–1.76)</td>
<td align="center" valign="top" charoff="50">0.186</td>
<td align="center" valign="top" charoff="50">0.120</td>
</tr>
</tbody>
</table>
<table-wrap-foot><fn id="t2-fn1"><p>AA, African Americans; ASW, AA ancestry; BCP-ALL, B-cell precursor acute lymphoblastic leukaemia; CI, confidence interval; EUR, European ancestry; HA, Hispanic Americans; LD, linkage disequilibrium; MXL, Hispanic ancestry; NA, Native Americans; OR, odds ratio; SNP, single-nucleotide polymorphism.</p>
</fn>
<fn id="t2-fn2"><p>Highlighted are SNPs with the smallest <italic>P</italic>
-values for each stage of the analysis (see <xref ref-type="table" rid="t1">Table 1</xref>
legend). rs662463 is the only SNP significantly associated with BCP-ALL in AAs (bold).</p>
</fn>
<fn id="t2-fn3"><p><sup>*</sup>
Correlation (<italic>r</italic>
<sup>2</sup>
) with rs77728904 in individuals of EUR, MXL and ASW in 1,000 Genomes Phase 1 (ref. <xref ref-type="bibr" rid="b17">17</xref>
).</p>
</fn>
<fn id="t2-fn4"><p><sup>†</sup>
Physical positions on chromosome 9 are from NCBI build 37/hg19.</p>
</fn>
<fn id="t2-fn5"><p><sup>‡</sup>
HA ancestry defined as >10% NA with % of NA>YRI (African ancestry).</p>
</fn>
<fn id="t2-fn6"><p><sup>§</sup>
AA ancestry defined as >70% YRI ancestry.</p>
</fn>
<fn id="t2-fn7"><p><sup>‖</sup>
SNPs in LD (<italic>r</italic>
<sup>2</sup>
>0.60) with rs77728904 and present in the discovery, replication and multi-ethnic analyses.</p>
</fn>
<fn id="t2-fn8"><p><sup>¶</sup>
1,000 Genomes population of Mexican ancestry from Los Angeles, CA, used as a proxy for HA ancestry.</p>
</fn>
<fn id="t2-fn9"><p><sup>#</sup>
1,000 Genomes population of African ancestry in Southwest USA, used as a proxy for AA ancestry.</p>
</fn>
<fn id="t2-fn10"><p><sup>**</sup>
OR with 95%CI.</p>
</fn>
<fn id="t2-fn11"><p><sup>††</sup>
Unconditional <italic>P</italic>
-values for listed SNPs.</p>
</fn>
<fn id="t2-fn12"><p><sup>‡‡</sup>
<italic>P</italic>
-values for listed SNPs when conditioned on rs3731217.</p>
</fn>
</table-wrap-foot>
</table-wrap>
</floats-group>
</pmc>
<affiliations><list><country><li>Allemagne</li>
<li>Australie</li>
<li>France</li>
<li>Pays-Bas</li>
<li>États-Unis</li>
</country>
</list>
<tree><country name="États-Unis"><noRegion><name sortKey="Hungate, Eric A" sort="Hungate, Eric A" uniqKey="Hungate E" first="Eric A." last="Hungate">Eric A. Hungate</name>
</noRegion>
<name sortKey="Best, Timothy" sort="Best, Timothy" uniqKey="Best T" first="Timothy" last="Best">Timothy Best</name>
<name sortKey="Cox, Nancy J" sort="Cox, Nancy J" uniqKey="Cox N" first="Nancy J." last="Cox">Nancy J. Cox</name>
<name sortKey="Gamazon, Eric R" sort="Gamazon, Eric R" uniqKey="Gamazon E" first="Eric R." last="Gamazon">Eric R. Gamazon</name>
<name sortKey="Hulur, Imge" sort="Hulur, Imge" uniqKey="Hulur I" first="Imge" last="Hulur">Imge Hulur</name>
<name sortKey="Lee, Younghee" sort="Lee, Younghee" uniqKey="Lee Y" first="Younghee" last="Lee">Younghee Lee</name>
<name sortKey="Loh, Mignon L" sort="Loh, Mignon L" uniqKey="Loh M" first="Mignon L." last="Loh">Mignon L. Loh</name>
<name sortKey="Moriyama, Takaya" sort="Moriyama, Takaya" uniqKey="Moriyama T" first="Takaya" last="Moriyama">Takaya Moriyama</name>
<name sortKey="Onel, Kenan" sort="Onel, Kenan" uniqKey="Onel K" first="Kenan" last="Onel">Kenan Onel</name>
<name sortKey="Pui, Ching Hon" sort="Pui, Ching Hon" uniqKey="Pui C" first="Ching-Hon" last="Pui">Ching-Hon Pui</name>
<name sortKey="Skol, Andrew D" sort="Skol, Andrew D" uniqKey="Skol A" first="Andrew D." last="Skol">Andrew D. Skol</name>
<name sortKey="Vora, Sapana R" sort="Vora, Sapana R" uniqKey="Vora S" first="Sapana R." last="Vora">Sapana R. Vora</name>
<name sortKey="Yang, Jun J" sort="Yang, Jun J" uniqKey="Yang J" first="Jun J." last="Yang">Jun J. Yang</name>
</country>
<country name="Pays-Bas"><noRegion><name sortKey="Gamazon, Eric R" sort="Gamazon, Eric R" uniqKey="Gamazon E" first="Eric R." last="Gamazon">Eric R. Gamazon</name>
</noRegion>
</country>
<country name="Australie"><noRegion><name sortKey="Evans, Tiffany Jane" sort="Evans, Tiffany Jane" uniqKey="Evans T" first="Tiffany-Jane" last="Evans">Tiffany-Jane Evans</name>
</noRegion>
<name sortKey="Milne, Elizabeth" sort="Milne, Elizabeth" uniqKey="Milne E" first="Elizabeth" last="Milne">Elizabeth Milne</name>
<name sortKey="Scott, Rodney J" sort="Scott, Rodney J" uniqKey="Scott R" first="Rodney J." last="Scott">Rodney J. Scott</name>
<name sortKey="Scott, Rodney J" sort="Scott, Rodney J" uniqKey="Scott R" first="Rodney J." last="Scott">Rodney J. Scott</name>
</country>
<country name="Allemagne"><noRegion><name sortKey="Ellinghaus, Eva" sort="Ellinghaus, Eva" uniqKey="Ellinghaus E" first="Eva" last="Ellinghaus">Eva Ellinghaus</name>
</noRegion>
<name sortKey="Stanulla, Martin" sort="Stanulla, Martin" uniqKey="Stanulla M" first="Martin" last="Stanulla">Martin Stanulla</name>
</country>
<country name="France"><noRegion><name sortKey="Rudant, Jeremie" sort="Rudant, Jeremie" uniqKey="Rudant J" first="Jéremie" last="Rudant">Jéremie Rudant</name>
</noRegion>
<name sortKey="Clavel, Jacqueline" sort="Clavel, Jacqueline" uniqKey="Clavel J" first="Jacqueline" last="Clavel">Jacqueline Clavel</name>
<name sortKey="Clavel, Jacqueline" sort="Clavel, Jacqueline" uniqKey="Clavel J" first="Jacqueline" last="Clavel">Jacqueline Clavel</name>
<name sortKey="Clavel, Jacqueline" sort="Clavel, Jacqueline" uniqKey="Clavel J" first="Jacqueline" last="Clavel">Jacqueline Clavel</name>
<name sortKey="Orsi, Laurent" sort="Orsi, Laurent" uniqKey="Orsi L" first="Laurent" last="Orsi">Laurent Orsi</name>
<name sortKey="Orsi, Laurent" sort="Orsi, Laurent" uniqKey="Orsi L" first="Laurent" last="Orsi">Laurent Orsi</name>
<name sortKey="Rudant, Jeremie" sort="Rudant, Jeremie" uniqKey="Rudant J" first="Jéremie" last="Rudant">Jéremie Rudant</name>
</country>
</tree>
</affiliations>
</record>
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