A genome-wide association study yields five novel thyroid cancer risk loci

Guðmundsson, Júlíus; Þorleifsson, Guðmar; Sigurðsson, Jón K.; Stefánsdóttir, Lilja; Jónasson, Jón G.; Guðjónsson, Sigurjón Axel; Gudbjartsson, Daniel; Másson, Gísli; Jóhannsdóttir, Hrefna; Halldórsson, Gísli H.; Stacey, Simon N.; Helgason, Hannes; sulem, patrick; Senter, Leigha; He, Huiling; Liyanarachchi, Sandya; Ringel, Matthew D.; Aguillo, Esperanza; Panadero, Angeles; Prats, Enrique; Garcia-Castaño, Almudena; De Juan, Ana; Rivera, Fernando; Xu, Li; Kiemeney, Lambertus A.; Eyjólfsson, Guðmundur I.; Sigurðardóttir, Ólöf; Ólafsson, Ísleifur; Kristvinsson, Höskuldur; Netea-Maier, Romana T.; Jónsson, Þorvaldur; Mayordomo, Jose I.; Plantinga, Theo S.; Hjartarson, Hannes; Hrafnkelsson, Jón; Sturgis, Erich M.; Þorsteinsdóttir, Unnur; Rafnar, Thorunn; de la Chapelle, Albert; Stefansson, Kari

Opin vísindi
→
Háskóli Íslands
→
Greinar- HÍ
→
Skoða verk

dc.contributor	Háskóli Íslands
dc.contributor	University of Iceland
dc.contributor.advisor
dc.contributor.author	Guðmundsson, Júlíus
dc.contributor.author	Þorleifsson, Guðmar
dc.contributor.author	Sigurðsson, Jón K.
dc.contributor.author	Stefánsdóttir, Lilja
dc.contributor.author	Jónasson, Jón G.
dc.contributor.author	Guðjónsson, Sigurjón Axel
dc.contributor.author	Gudbjartsson, Daniel
dc.contributor.author	orcid.org/0000-0003-0493-8242 Másson, Gísli
dc.contributor.author	Jóhannsdóttir, Hrefna
dc.contributor.author	Halldórsson, Gísli H.
dc.contributor.author	Stacey, Simon N.
dc.contributor.author	Helgason, Hannes
dc.contributor.author	orcid.org/0000-0001-7123-6123 sulem, patrick
dc.contributor.author	Senter, Leigha
dc.contributor.author	He, Huiling
dc.contributor.author	Liyanarachchi, Sandya
dc.contributor.author	Ringel, Matthew D.
dc.contributor.author	Aguillo, Esperanza
dc.contributor.author	Panadero, Angeles
dc.contributor.author	Prats, Enrique
dc.contributor.author	Garcia-Castaño, Almudena
dc.contributor.author	De Juan, Ana
dc.contributor.author	Rivera, Fernando
dc.contributor.author	Xu, Li
dc.contributor.author	Kiemeney, Lambertus A.
dc.contributor.author	Eyjólfsson, Guðmundur I.
dc.contributor.author	Sigurðardóttir, Ólöf
dc.contributor.author	Ólafsson, Ísleifur
dc.contributor.author	Kristvinsson, Höskuldur
dc.contributor.author	Netea-Maier, Romana T.
dc.contributor.author	Jónsson, Þorvaldur
dc.contributor.author	Mayordomo, Jose I.
dc.contributor.author	Plantinga, Theo S.
dc.contributor.author	Hjartarson, Hannes
dc.contributor.author	Hrafnkelsson, Jón
dc.contributor.author	Sturgis, Erich M.
dc.contributor.author	Þorsteinsdóttir, Unnur
dc.contributor.author	orcid.org/0000-0003-0491-7046 Rafnar, Thorunn
dc.contributor.author	de la Chapelle, Albert
dc.contributor.author	orcid.org/0000-0003-1676-864X Stefansson, Kari
dc.date.accessioned	2017-06-14T13:58:15Z
dc.date.available	2017-06-14T13:58:15Z
dc.date.issued	2017-02-14
dc.identifier.citation	Gudmundsson, J. et al. A genome-wide association study yields five novel thyroid cancer risk loci. Nat. Commun. 8, 14517 doi: 10.1038/ncomms14517 (2017).
dc.identifier.issn	2041-1723
dc.identifier.uri	https://hdl.handle.net/20.500.11815/304
dc.description.abstract	The great majority of thyroid cancers are of the non-medullary type. Here we report findings from a genome-wide association study of non-medullary thyroid cancer, including in total 3,001 patients and 287,550 controls from five study groups of European descent. Our results yield five novel loci (all with Pcombined<3 × 10−8): 1q42.2 (rs12129938 in PCNXL2), 3q26.2 (rs6793295 a missense mutation in LRCC34 near TERC), 5q22.1 (rs73227498 between NREP and EPB41L4A), 10q24.33 (rs7902587 near OBFC1), and two independently associated variants at 15q22.33 (rs2289261 and rs56062135; both in SMAD3). We also confirm recently published association results from a Chinese study of a variant on 5p15.33 (rs2736100 near the TERT gene) and present a stronger association result for a moderately correlated variant (rs10069690; OR=1.20, P=3.2 × 10−7) based on our study of individuals of European ancestry. In combination, these results raise several opportunities for future studies of the pathogenesis of thyroid cancer.
dc.description.sponsorship	We thank the patients whose contribution made this work possible. The study was supported in part by grants from the National Institutes of Health: CA16058 (to the Ohio State University Comprehensive Cancer Center) and CA168505 (to M.D.R. and A.d.l.C.). This work was supported in part by The University of Texas MD Anderson Cancer Center start-up funds (to E.M.S.); an American Thyroid Association research grant (to E.M.S.), National Institutes of Health (NIH) grant U01 DE019765-01 (to E.M.S.); and Cancer Center Support Grant CA016672 to the University of Texas MD Anderson Cancer Center. This study makes use of data generated by the Genome of the Netherlands Project (GoNL). A full list of the investigators is available from http://www.nlgenome.nl. Funding for the GoNL project was provided by the Netherlands Organization for Scientific Research under award number 184021007, dated 9 July 2009 and made available as a Rainbow Project of the Biobanking and Biomolecular Research Infrastructure Netherlands (BBMRI-NL). The sequencing was carried out in collaboration with the Beijing Institute for Genomics (BGI). This study also makes use of data generated by the GTEx Consortium and we are grateful for early stage sharing of RNA-seq and genotypic data. The following acknowledgement refers to the GTEx data: The Genotype-Tissue Expression (GTEx) Project was supported by the Common Fund of the Office of the Director of the National Institutes of Health. Additional funds were provided by the NCI, NHGRI, NHLBI, NIDA, NIMH and NINDS. Donors were enrolled at Biospecimen Source Sites funded by NCI\SAIC-Frederick, Inc. (SAIC-F) subcontracts to the National Disease Research Interchange (10XS170), Roswell Park Cancer Institute (10XS171) and Science Care, Inc. (X10S172). The Laboratory, Data Analysis and Coordinating Center (LDACC) was funded through a contract (HHSN268201000029C) to The Broad Institute, Inc. Biorepository operations were funded through an SAIC-F subcontract to Van Andel Institute (10ST1035). Additional data repository and project management were provided by SAIC-F (HHSN261200800001E). The Brain Bank was supported by supplements to University of Miami grants DA006227 and DA033684 and to contract N01MH000028. Statistical Methods development grants were made to the University of Geneva (MH090941 and MH101814), the University of Chicago (MH090951, MH090937, MH101820 and MH101825), the University of North Carolina—Chapel Hill (MH090936 and MH101819), Harvard University (MH090948), Stanford University (MH101782), Washington University St Louis (MH101810) and the University of Pennsylvania (MH101822).
dc.format.extent	14517
dc.language.iso	en
dc.publisher	Springer Nature
dc.relation.ispartofseries	Nature Communications;8
dc.rights	info:eu-repo/semantics/openAccess
dc.subject	Cancer genetics
dc.subject	Genome-wide association studies
dc.subject	Krabbamein
dc.subject	Erfðafræði
dc.subject	Rannsóknir
dc.title	A genome-wide association study yields five novel thyroid cancer risk loci
dc.type	info:eu-repo/semantics/article
dcterms.license	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 http://creativecommons.org/licenses/by/4.0/
dc.description.version	Peer Reviewed
dc.identifier.journal	Nature Communications
dc.identifier.doi	10.1038/ncomms14517
dc.relation.url	https://www.nature.com/articles/ncomms14517
dc.contributor.department	Læknadeild (HÍ)
dc.contributor.department	Faculty of Medicine (UI)
dc.contributor.school	Heilbrigðisvísindasvið (HÍ)
dc.contributor.school	School of Health Sciences (UI)
dc.contributor.school	Verkfræði- og náttúruvísindasvið (HÍ)
dc.contributor.school	School of Engineering and Natural Sciences (UI)