Serveur d'exploration sur les relations entre la France et l'Australie

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Fine-Mapping of Common Genetic Variants Associated with Colorectal Tumor Risk Identified Potential Functional Variants

Identifieur interne : 001E89 ( Main/Exploration ); précédent : 001E88; suivant : 001E90

Fine-Mapping of Common Genetic Variants Associated with Colorectal Tumor Risk Identified Potential Functional Variants

Auteurs : Mengmeng Du [États-Unis] ; Shuo Jiao [États-Unis] ; Stephanie A. Bien [États-Unis] ; Manish Gala [États-Unis] ; Goncalo Abecasis [États-Unis] ; Stephane Bezieau [France] ; Hermann Brenner [Allemagne] ; Katja Butterbach [Allemagne] ; Bette J. Caan [États-Unis] ; Christopher S. Carlson [États-Unis] ; Graham Casey [États-Unis] ; Jenny Chang-Claude [Allemagne] ; David V. Conti [États-Unis] ; Keith R. Curtis [États-Unis] ; David Duggan [États-Unis] ; Steven Gallinger [Canada] ; Robert W. Haile [États-Unis] ; Tabitha A. Harrison [États-Unis] ; Richard B. Hayes [États-Unis] ; Michael Hoffmeister [Allemagne] ; John L. Hopper [Australie] ; Thomas J. Hudson [Canada] ; Mark A. Jenkins [Australie] ; Sébastien Küry [France] ; Loic Le Marchand [États-Unis] ; Suzanne M. Leal [États-Unis] ; Polly A. Newcomb [États-Unis] ; Deborah A. Nickerson [États-Unis] ; John D. Potter [États-Unis, Nouvelle-Zélande] ; Robert E. Schoen [États-Unis] ; Fredrick R. Schumacher [États-Unis] ; Daniela Seminara [États-Unis] ; Martha L. Slattery [États-Unis] ; Li Hsu [États-Unis] ; Andrew T. Chan [États-Unis] ; Emily White [États-Unis] ; Sonja I. Berndt [États-Unis] ; Ulrike Peters [États-Unis]

Source :

RBID : PMC:4933364

Descripteurs français

English descriptors

Abstract

Genome-wide association studies (GWAS) have identified many common single nucleotide polymorphisms (SNPs) associated with colorectal cancer risk. These SNPs may tag correlated variants with biological importance. Fine-mapping around GWAS loci can facilitate detection of functional candidates and additional independent risk variants. We analyzed 11,900 cases and 14,311 controls in the Genetics and Epidemiology of Colorectal Cancer Consortium and the Colon Cancer Family Registry. To fine-map genomic regions containing all known common risk variants, we imputed high-density genetic data from the 1000 Genomes Project. We tested single-variant associations with colorectal tumor risk for all variants spanning genomic regions 250-kb upstream or downstream of 31 GWAS-identified SNPs (index SNPs). We queried the University of California, Santa Cruz Genome Browser to examine evidence for biological function. Index SNPs did not show the strongest association signals with colorectal tumor risk in their respective genomic regions. Bioinformatics analysis of SNPs showing smaller P-values in each region revealed 21 functional candidates in 12 loci (5q31.1, 8q24, 11q13.4, 11q23, 12p13.32, 12q24.21, 14q22.2, 15q13, 18q21, 19q13.1, 20p12.3, and 20q13.33). We did not observe evidence of additional independent association signals in GWAS-identified regions. Our results support the utility of integrating data from comprehensive fine-mapping with expanding publicly available genomic databases to help clarify GWAS associations and identify functional candidates that warrant more onerous laboratory follow-up. Such efforts may aid the eventual discovery of disease-causing variant(s).


Url:
DOI: 10.1371/journal.pone.0157521
PubMed: 27379672
PubMed Central: 4933364


Affiliations:


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Le document en format XML

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<name sortKey="Chang Claude, Jenny" sort="Chang Claude, Jenny" uniqKey="Chang Claude J" first="Jenny" last="Chang-Claude">Jenny Chang-Claude</name>
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<region type="state">Washington (État)</region>
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<title xml:lang="en" level="a" type="main">Fine-Mapping of Common Genetic Variants Associated with Colorectal Tumor Risk Identified Potential Functional Variants</title>
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</nlm:aff>
<country xml:lang="fr">Allemagne</country>
<wicri:regionArea>Division of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ), Heidelberg</wicri:regionArea>
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<region type="state">Washington (État)</region>
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</placeName>
<orgName type="university">Université de Californie du Sud</orgName>
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<nlm:aff id="aff011">
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</nlm:aff>
<country xml:lang="fr">Allemagne</country>
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</placeName>
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</placeName>
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</author>
<author>
<name sortKey="Hayes, Richard B" sort="Hayes, Richard B" uniqKey="Hayes R" first="Richard B." last="Hayes">Richard B. Hayes</name>
<affiliation wicri:level="2">
<nlm:aff id="aff014">
<addr-line>Division of Epidemiology, Department of Population Health, New York University School of Medicine, New York, NY, United States of America</addr-line>
</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Division of Epidemiology, Department of Population Health, New York University School of Medicine, New York, NY</wicri:regionArea>
<placeName>
<region type="state">État de New York</region>
</placeName>
</affiliation>
</author>
<author>
<name sortKey="Hoffmeister, Michael" sort="Hoffmeister, Michael" uniqKey="Hoffmeister M" first="Michael" last="Hoffmeister">Michael Hoffmeister</name>
<affiliation wicri:level="3">
<nlm:aff id="aff007">
<addr-line>Division of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ), Heidelberg, Germany</addr-line>
</nlm:aff>
<country xml:lang="fr">Allemagne</country>
<wicri:regionArea>Division of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ), Heidelberg</wicri:regionArea>
<placeName>
<region type="land" nuts="1">Bade-Wurtemberg</region>
<region type="district" nuts="2">District de Karlsruhe</region>
<settlement type="city">Heidelberg</settlement>
</placeName>
</affiliation>
</author>
<author>
<name sortKey="Hopper, John L" sort="Hopper, John L" uniqKey="Hopper J" first="John L." last="Hopper">John L. Hopper</name>
<affiliation wicri:level="4">
<nlm:aff id="aff015">
<addr-line>Melbourne School of Population and Global Health, The University of Melbourne, Melbourne, Victoria, Australia</addr-line>
</nlm:aff>
<country xml:lang="fr">Australie</country>
<wicri:regionArea>Melbourne School of Population and Global Health, The University of Melbourne, Melbourne, Victoria</wicri:regionArea>
<orgName type="university">Université de Melbourne</orgName>
<placeName>
<settlement type="city">Melbourne</settlement>
<region type="état">Victoria (État)</region>
</placeName>
</affiliation>
</author>
<author>
<name sortKey="Hudson, Thomas J" sort="Hudson, Thomas J" uniqKey="Hudson T" first="Thomas J." last="Hudson">Thomas J. Hudson</name>
<affiliation wicri:level="1">
<nlm:aff id="aff016">
<addr-line>Ontario Institute for Cancer Research, Toronto, ON, Canada</addr-line>
</nlm:aff>
<country xml:lang="fr">Canada</country>
<wicri:regionArea>Ontario Institute for Cancer Research, Toronto, ON</wicri:regionArea>
<wicri:noRegion>ON</wicri:noRegion>
</affiliation>
<affiliation wicri:level="4">
<nlm:aff id="aff017">
<addr-line>Departments of Medical Biophysics and Molecular Genetics, University of Toronto, Toronto, ON, Canada</addr-line>
</nlm:aff>
<country xml:lang="fr">Canada</country>
<wicri:regionArea>Departments of Medical Biophysics and Molecular Genetics, University of Toronto, Toronto, ON</wicri:regionArea>
<orgName type="university">Université de Toronto</orgName>
<placeName>
<settlement type="city">Toronto</settlement>
<region type="state">Ontario</region>
</placeName>
</affiliation>
</author>
<author>
<name sortKey="Jenkins, Mark A" sort="Jenkins, Mark A" uniqKey="Jenkins M" first="Mark A." last="Jenkins">Mark A. Jenkins</name>
<affiliation wicri:level="4">
<nlm:aff id="aff015">
<addr-line>Melbourne School of Population and Global Health, The University of Melbourne, Melbourne, Victoria, Australia</addr-line>
</nlm:aff>
<country xml:lang="fr">Australie</country>
<wicri:regionArea>Melbourne School of Population and Global Health, The University of Melbourne, Melbourne, Victoria</wicri:regionArea>
<orgName type="university">Université de Melbourne</orgName>
<placeName>
<settlement type="city">Melbourne</settlement>
<region type="état">Victoria (État)</region>
</placeName>
</affiliation>
</author>
<author>
<name sortKey="Kury, Sebastien" sort="Kury, Sebastien" uniqKey="Kury S" first="Sébastien" last="Küry">Sébastien Küry</name>
<affiliation wicri:level="3">
<nlm:aff id="aff006">
<addr-line>Service de Génétique Médicale, CHU Nantes, Nantes, France</addr-line>
</nlm:aff>
<country xml:lang="fr">France</country>
<wicri:regionArea>Service de Génétique Médicale, CHU Nantes, Nantes</wicri:regionArea>
<placeName>
<region type="region">Pays de la Loire</region>
<region type="old region">Pays de la Loire</region>
<settlement type="city">Nantes</settlement>
</placeName>
</affiliation>
</author>
<author>
<name sortKey="Le Marchand, Loic" sort="Le Marchand, Loic" uniqKey="Le Marchand L" first="Loic" last="Le Marchand">Loic Le Marchand</name>
<affiliation wicri:level="2">
<nlm:aff id="aff018">
<addr-line>Epidemiology Program, University of Hawaii Cancer Center, Honolulu, HI, United States of America</addr-line>
</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Epidemiology Program, University of Hawaii Cancer Center, Honolulu, HI</wicri:regionArea>
<placeName>
<region type="state">Hawaï</region>
</placeName>
</affiliation>
</author>
<author>
<name sortKey="Leal, Suzanne M" sort="Leal, Suzanne M" uniqKey="Leal S" first="Suzanne M." last="Leal">Suzanne M. Leal</name>
<affiliation wicri:level="2">
<nlm:aff id="aff019">
<addr-line>Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX, United States of America</addr-line>
</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX</wicri:regionArea>
<placeName>
<region type="state">Texas</region>
</placeName>
</affiliation>
</author>
<author>
<name sortKey="Newcomb, Polly A" sort="Newcomb, Polly A" uniqKey="Newcomb P" first="Polly A." last="Newcomb">Polly A. Newcomb</name>
<affiliation wicri:level="2">
<nlm:aff id="aff002">
<addr-line>Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, WA, United States of America</addr-line>
</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, WA</wicri:regionArea>
<placeName>
<region type="state">Washington (État)</region>
</placeName>
</affiliation>
<affiliation wicri:level="4">
<nlm:aff id="aff003">
<addr-line>School of Public Health, University of Washington, Seattle, WA, United States of America</addr-line>
</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>School of Public Health, University of Washington, Seattle, WA</wicri:regionArea>
<placeName>
<region type="state">Washington (État)</region>
<settlement type="city">Seattle</settlement>
</placeName>
<orgName type="university">Université de Washington</orgName>
</affiliation>
</author>
<author>
<name sortKey="Nickerson, Deborah A" sort="Nickerson, Deborah A" uniqKey="Nickerson D" first="Deborah A." last="Nickerson">Deborah A. Nickerson</name>
<affiliation wicri:level="4">
<nlm:aff id="aff020">
<addr-line>Genome Sciences, University of Washington, Seattle, WA, United States of America</addr-line>
</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Genome Sciences, University of Washington, Seattle, WA</wicri:regionArea>
<placeName>
<region type="state">Washington (État)</region>
<settlement type="city">Seattle</settlement>
</placeName>
<orgName type="university">Université de Washington</orgName>
</affiliation>
</author>
<author>
<name sortKey="Potter, John D" sort="Potter, John D" uniqKey="Potter J" first="John D." last="Potter">John D. Potter</name>
<affiliation wicri:level="2">
<nlm:aff id="aff002">
<addr-line>Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, WA, United States of America</addr-line>
</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, WA</wicri:regionArea>
<placeName>
<region type="state">Washington (État)</region>
</placeName>
</affiliation>
<affiliation wicri:level="4">
<nlm:aff id="aff003">
<addr-line>School of Public Health, University of Washington, Seattle, WA, United States of America</addr-line>
</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>School of Public Health, University of Washington, Seattle, WA</wicri:regionArea>
<placeName>
<region type="state">Washington (État)</region>
<settlement type="city">Seattle</settlement>
</placeName>
<orgName type="university">Université de Washington</orgName>
</affiliation>
<affiliation wicri:level="1">
<nlm:aff id="aff021">
<addr-line>Centre for Public Health Research, Massey University, Wellington, New Zealand</addr-line>
</nlm:aff>
<country xml:lang="fr">Nouvelle-Zélande</country>
<wicri:regionArea>Centre for Public Health Research, Massey University, Wellington</wicri:regionArea>
<wicri:noRegion>Wellington</wicri:noRegion>
</affiliation>
</author>
<author>
<name sortKey="Schoen, Robert E" sort="Schoen, Robert E" uniqKey="Schoen R" first="Robert E." last="Schoen">Robert E. Schoen</name>
<affiliation wicri:level="2">
<nlm:aff id="aff022">
<addr-line>Department of Medicine and Epidemiology, University of Pittsburgh Medical Center, Pittsburgh, PA, United States of America</addr-line>
</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Department of Medicine and Epidemiology, University of Pittsburgh Medical Center, Pittsburgh, PA</wicri:regionArea>
<placeName>
<region type="state">Pennsylvanie</region>
</placeName>
</affiliation>
</author>
<author>
<name sortKey="Schumacher, Fredrick R" sort="Schumacher, Fredrick R" uniqKey="Schumacher F" first="Fredrick R." last="Schumacher">Fredrick R. Schumacher</name>
<affiliation wicri:level="4">
<nlm:aff id="aff010">
<addr-line>Keck School of Medicine, University of Southern California, Los Angeles, CA, United States of America</addr-line>
</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Keck School of Medicine, University of Southern California, Los Angeles, CA</wicri:regionArea>
<placeName>
<region type="state">Californie</region>
<settlement type="city">Los Angeles</settlement>
</placeName>
<orgName type="university">Université de Californie du Sud</orgName>
</affiliation>
</author>
<author>
<name sortKey="Seminara, Daniela" sort="Seminara, Daniela" uniqKey="Seminara D" first="Daniela" last="Seminara">Daniela Seminara</name>
<affiliation wicri:level="2">
<nlm:aff id="aff023">
<addr-line>Division of Cancer Control and Population Sciences, National Cancer Institute, Bethesda, MD, United States of America</addr-line>
</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Division of Cancer Control and Population Sciences, National Cancer Institute, Bethesda, MD</wicri:regionArea>
<placeName>
<region type="state">Maryland</region>
</placeName>
</affiliation>
</author>
<author>
<name sortKey="Slattery, Martha L" sort="Slattery, Martha L" uniqKey="Slattery M" first="Martha L." last="Slattery">Martha L. Slattery</name>
<affiliation wicri:level="2">
<nlm:aff id="aff024">
<addr-line>Department of Internal Medicine, University of Utah Health Sciences Center, Salt Lake City, UT, United States of America</addr-line>
</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Department of Internal Medicine, University of Utah Health Sciences Center, Salt Lake City, UT</wicri:regionArea>
<placeName>
<region type="state">Utah</region>
</placeName>
</affiliation>
</author>
<author>
<name sortKey="Hsu, Li" sort="Hsu, Li" uniqKey="Hsu L" first="Li" last="Hsu">Li Hsu</name>
<affiliation wicri:level="2">
<nlm:aff id="aff002">
<addr-line>Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, WA, United States of America</addr-line>
</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, WA</wicri:regionArea>
<placeName>
<region type="state">Washington (État)</region>
</placeName>
</affiliation>
</author>
<author>
<name sortKey="Chan, Andrew T" sort="Chan, Andrew T" uniqKey="Chan A" first="Andrew T." last="Chan">Andrew T. Chan</name>
<affiliation wicri:level="2">
<nlm:aff id="aff004">
<addr-line>Division of Gastroenterology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, United States of America</addr-line>
</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Division of Gastroenterology, Massachusetts General Hospital and Harvard Medical School, Boston, MA</wicri:regionArea>
<placeName>
<region type="state">Massachusetts</region>
</placeName>
</affiliation>
<affiliation wicri:level="2">
<nlm:aff id="aff025">
<addr-line>Channing Division of Network Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, United States of America</addr-line>
</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Channing Division of Network Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA</wicri:regionArea>
<placeName>
<region type="state">Massachusetts</region>
</placeName>
</affiliation>
</author>
<author>
<name sortKey="White, Emily" sort="White, Emily" uniqKey="White E" first="Emily" last="White">Emily White</name>
<affiliation wicri:level="2">
<nlm:aff id="aff002">
<addr-line>Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, WA, United States of America</addr-line>
</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, WA</wicri:regionArea>
<placeName>
<region type="state">Washington (État)</region>
</placeName>
</affiliation>
<affiliation wicri:level="4">
<nlm:aff id="aff003">
<addr-line>School of Public Health, University of Washington, Seattle, WA, United States of America</addr-line>
</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>School of Public Health, University of Washington, Seattle, WA</wicri:regionArea>
<placeName>
<region type="state">Washington (État)</region>
<settlement type="city">Seattle</settlement>
</placeName>
<orgName type="university">Université de Washington</orgName>
</affiliation>
</author>
<author>
<name sortKey="Berndt, Sonja I" sort="Berndt, Sonja I" uniqKey="Berndt S" first="Sonja I." last="Berndt">Sonja I. Berndt</name>
<affiliation wicri:level="2">
<nlm:aff id="aff026">
<addr-line>Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD, United States of America</addr-line>
</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD</wicri:regionArea>
<placeName>
<region type="state">Maryland</region>
</placeName>
</affiliation>
</author>
<author>
<name sortKey="Peters, Ulrike" sort="Peters, Ulrike" uniqKey="Peters U" first="Ulrike" last="Peters">Ulrike Peters</name>
<affiliation wicri:level="2">
<nlm:aff id="aff002">
<addr-line>Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, WA, United States of America</addr-line>
</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, WA</wicri:regionArea>
<placeName>
<region type="state">Washington (État)</region>
</placeName>
</affiliation>
<affiliation wicri:level="4">
<nlm:aff id="aff003">
<addr-line>School of Public Health, University of Washington, Seattle, WA, United States of America</addr-line>
</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>School of Public Health, University of Washington, Seattle, WA</wicri:regionArea>
<placeName>
<region type="state">Washington (État)</region>
<settlement type="city">Seattle</settlement>
</placeName>
<orgName type="university">Université de Washington</orgName>
</affiliation>
</author>
</analytic>
<series>
<title level="j">PLoS ONE</title>
<idno type="eISSN">1932-6203</idno>
<imprint>
<date when="2016">2016</date>
</imprint>
</series>
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<keywords scheme="KwdEn" xml:lang="en">
<term>A549 Cells</term>
<term>Adult</term>
<term>Aged</term>
<term>Aged, 80 and over</term>
<term>Caco-2 Cells</term>
<term>Chromosome Mapping</term>
<term>Colorectal Neoplasms (genetics)</term>
<term>Colorectal Neoplasms (pathology)</term>
<term>Computational Biology (methods)</term>
<term>Female</term>
<term>Genetic Predisposition to Disease (genetics)</term>
<term>Genetic Variation</term>
<term>Genome-Wide Association Study (methods)</term>
<term>Genotype</term>
<term>HCT116 Cells</term>
<term>Hep G2 Cells</term>
<term>Humans</term>
<term>Male</term>
<term>Middle Aged</term>
<term>Polymorphism, Single Nucleotide</term>
<term>Registries (statistics & numerical data)</term>
<term>Risk Factors</term>
<term>Young Adult</term>
</keywords>
<keywords scheme="KwdFr" xml:lang="fr">
<term>Adulte</term>
<term>Adulte d'âge moyen</term>
<term>Biologie informatique ()</term>
<term>Cartographie chromosomique</term>
<term>Cellules A549</term>
<term>Cellules Caco-2</term>
<term>Cellules HCT116</term>
<term>Cellules HepG2</term>
<term>Enregistrements ()</term>
<term>Facteurs de risque</term>
<term>Femelle</term>
<term>Génotype</term>
<term>Humains</term>
<term>Jeune adulte</term>
<term>Mâle</term>
<term>Polymorphisme de nucléotide simple</term>
<term>Prédisposition génétique à une maladie (génétique)</term>
<term>Sujet âgé</term>
<term>Sujet âgé de 80 ans ou plus</term>
<term>Tumeurs colorectales (anatomopathologie)</term>
<term>Tumeurs colorectales (génétique)</term>
<term>Variation génétique</term>
<term>Étude d'association pangénomique ()</term>
</keywords>
<keywords scheme="MESH" qualifier="anatomopathologie" xml:lang="fr">
<term>Tumeurs colorectales</term>
</keywords>
<keywords scheme="MESH" qualifier="genetics" xml:lang="en">
<term>Colorectal Neoplasms</term>
<term>Genetic Predisposition to Disease</term>
</keywords>
<keywords scheme="MESH" qualifier="génétique" xml:lang="fr">
<term>Prédisposition génétique à une maladie</term>
<term>Tumeurs colorectales</term>
</keywords>
<keywords scheme="MESH" qualifier="methods" xml:lang="en">
<term>Computational Biology</term>
<term>Genome-Wide Association Study</term>
</keywords>
<keywords scheme="MESH" qualifier="pathology" xml:lang="en">
<term>Colorectal Neoplasms</term>
</keywords>
<keywords scheme="MESH" qualifier="statistics & numerical data" xml:lang="en">
<term>Registries</term>
</keywords>
<keywords scheme="MESH" xml:lang="en">
<term>A549 Cells</term>
<term>Adult</term>
<term>Aged</term>
<term>Aged, 80 and over</term>
<term>Caco-2 Cells</term>
<term>Chromosome Mapping</term>
<term>Female</term>
<term>Genetic Variation</term>
<term>Genotype</term>
<term>HCT116 Cells</term>
<term>Hep G2 Cells</term>
<term>Humans</term>
<term>Male</term>
<term>Middle Aged</term>
<term>Polymorphism, Single Nucleotide</term>
<term>Risk Factors</term>
<term>Young Adult</term>
</keywords>
<keywords scheme="MESH" xml:lang="fr">
<term>Adulte</term>
<term>Adulte d'âge moyen</term>
<term>Biologie informatique</term>
<term>Cartographie chromosomique</term>
<term>Cellules A549</term>
<term>Cellules Caco-2</term>
<term>Cellules HCT116</term>
<term>Cellules HepG2</term>
<term>Enregistrements</term>
<term>Facteurs de risque</term>
<term>Femelle</term>
<term>Génotype</term>
<term>Humains</term>
<term>Jeune adulte</term>
<term>Mâle</term>
<term>Polymorphisme de nucléotide simple</term>
<term>Sujet âgé</term>
<term>Sujet âgé de 80 ans ou plus</term>
<term>Variation génétique</term>
<term>Étude d'association pangénomique</term>
</keywords>
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<front>
<div type="abstract" xml:lang="en">
<p>Genome-wide association studies (GWAS) have identified many common single nucleotide polymorphisms (SNPs) associated with colorectal cancer risk. These SNPs may tag correlated variants with biological importance. Fine-mapping around GWAS loci can facilitate detection of functional candidates and additional independent risk variants. We analyzed 11,900 cases and 14,311 controls in the Genetics and Epidemiology of Colorectal Cancer Consortium and the Colon Cancer Family Registry. To fine-map genomic regions containing all known common risk variants, we imputed high-density genetic data from the 1000 Genomes Project. We tested single-variant associations with colorectal tumor risk for all variants spanning genomic regions 250-kb upstream or downstream of 31 GWAS-identified SNPs (index SNPs). We queried the University of California, Santa Cruz Genome Browser to examine evidence for biological function. Index SNPs did not show the strongest association signals with colorectal tumor risk in their respective genomic regions. Bioinformatics analysis of SNPs showing smaller
<italic>P</italic>
-values in each region revealed 21 functional candidates in 12 loci (5q31.1, 8q24, 11q13.4, 11q23, 12p13.32, 12q24.21, 14q22.2, 15q13, 18q21, 19q13.1, 20p12.3, and 20q13.33). We did not observe evidence of additional independent association signals in GWAS-identified regions. Our results support the utility of integrating data from comprehensive fine-mapping with expanding publicly available genomic databases to help clarify GWAS associations and identify functional candidates that warrant more onerous laboratory follow-up. Such efforts may aid the eventual discovery of disease-causing variant(s).</p>
</div>
</front>
<back>
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<author>
<name sortKey="Rosenberg, Na" uniqKey="Rosenberg N">NA Rosenberg</name>
</author>
</analytic>
</biblStruct>
<biblStruct>
<analytic>
<author>
<name sortKey="Zheng, J" uniqKey="Zheng J">J Zheng</name>
</author>
<author>
<name sortKey="Li, Y" uniqKey="Li Y">Y Li</name>
</author>
<author>
<name sortKey="Abecasis, Gr" uniqKey="Abecasis G">GR Abecasis</name>
</author>
<author>
<name sortKey="Scheet, P" uniqKey="Scheet P">P Scheet</name>
</author>
</analytic>
</biblStruct>
</listBibl>
</div1>
</back>
</TEI>
<affiliations>
<list>
<country>
<li>Allemagne</li>
<li>Australie</li>
<li>Canada</li>
<li>France</li>
<li>Nouvelle-Zélande</li>
<li>États-Unis</li>
</country>
<region>
<li>Arizona</li>
<li>Bade-Wurtemberg</li>
<li>Californie</li>
<li>District de Karlsruhe</li>
<li>Hawaï</li>
<li>Maryland</li>
<li>Massachusetts</li>
<li>Michigan</li>
<li>Ontario</li>
<li>Pays de la Loire</li>
<li>Pennsylvanie</li>
<li>Texas</li>
<li>Utah</li>
<li>Victoria (État)</li>
<li>Washington (État)</li>
<li>État de New York</li>
</region>
<settlement>
<li>Heidelberg</li>
<li>Los Angeles</li>
<li>Melbourne</li>
<li>Nantes</li>
<li>Seattle</li>
<li>Toronto</li>
</settlement>
<orgName>
<li>Université de Californie du Sud</li>
<li>Université de Melbourne</li>
<li>Université de Toronto</li>
<li>Université de Washington</li>
</orgName>
</list>
<tree>
<country name="États-Unis">
<region name="État de New York">
<name sortKey="Du, Mengmeng" sort="Du, Mengmeng" uniqKey="Du M" first="Mengmeng" last="Du">Mengmeng Du</name>
</region>
<name sortKey="Abecasis, Goncalo" sort="Abecasis, Goncalo" uniqKey="Abecasis G" first="Goncalo" last="Abecasis">Goncalo Abecasis</name>
<name sortKey="Berndt, Sonja I" sort="Berndt, Sonja I" uniqKey="Berndt S" first="Sonja I." last="Berndt">Sonja I. Berndt</name>
<name sortKey="Bien, Stephanie A" sort="Bien, Stephanie A" uniqKey="Bien S" first="Stephanie A." last="Bien">Stephanie A. Bien</name>
<name sortKey="Bien, Stephanie A" sort="Bien, Stephanie A" uniqKey="Bien S" first="Stephanie A." last="Bien">Stephanie A. Bien</name>
<name sortKey="Caan, Bette J" sort="Caan, Bette J" uniqKey="Caan B" first="Bette J." last="Caan">Bette J. Caan</name>
<name sortKey="Carlson, Christopher S" sort="Carlson, Christopher S" uniqKey="Carlson C" first="Christopher S." last="Carlson">Christopher S. Carlson</name>
<name sortKey="Casey, Graham" sort="Casey, Graham" uniqKey="Casey G" first="Graham" last="Casey">Graham Casey</name>
<name sortKey="Chan, Andrew T" sort="Chan, Andrew T" uniqKey="Chan A" first="Andrew T." last="Chan">Andrew T. Chan</name>
<name sortKey="Chan, Andrew T" sort="Chan, Andrew T" uniqKey="Chan A" first="Andrew T." last="Chan">Andrew T. Chan</name>
<name sortKey="Conti, David V" sort="Conti, David V" uniqKey="Conti D" first="David V." last="Conti">David V. Conti</name>
<name sortKey="Curtis, Keith R" sort="Curtis, Keith R" uniqKey="Curtis K" first="Keith R." last="Curtis">Keith R. Curtis</name>
<name sortKey="Du, Mengmeng" sort="Du, Mengmeng" uniqKey="Du M" first="Mengmeng" last="Du">Mengmeng Du</name>
<name sortKey="Duggan, David" sort="Duggan, David" uniqKey="Duggan D" first="David" last="Duggan">David Duggan</name>
<name sortKey="Gala, Manish" sort="Gala, Manish" uniqKey="Gala M" first="Manish" last="Gala">Manish Gala</name>
<name sortKey="Haile, Robert W" sort="Haile, Robert W" uniqKey="Haile R" first="Robert W." last="Haile">Robert W. Haile</name>
<name sortKey="Harrison, Tabitha A" sort="Harrison, Tabitha A" uniqKey="Harrison T" first="Tabitha A." last="Harrison">Tabitha A. Harrison</name>
<name sortKey="Hayes, Richard B" sort="Hayes, Richard B" uniqKey="Hayes R" first="Richard B." last="Hayes">Richard B. Hayes</name>
<name sortKey="Hsu, Li" sort="Hsu, Li" uniqKey="Hsu L" first="Li" last="Hsu">Li Hsu</name>
<name sortKey="Jiao, Shuo" sort="Jiao, Shuo" uniqKey="Jiao S" first="Shuo" last="Jiao">Shuo Jiao</name>
<name sortKey="Le Marchand, Loic" sort="Le Marchand, Loic" uniqKey="Le Marchand L" first="Loic" last="Le Marchand">Loic Le Marchand</name>
<name sortKey="Leal, Suzanne M" sort="Leal, Suzanne M" uniqKey="Leal S" first="Suzanne M." last="Leal">Suzanne M. Leal</name>
<name sortKey="Newcomb, Polly A" sort="Newcomb, Polly A" uniqKey="Newcomb P" first="Polly A." last="Newcomb">Polly A. Newcomb</name>
<name sortKey="Newcomb, Polly A" sort="Newcomb, Polly A" uniqKey="Newcomb P" first="Polly A." last="Newcomb">Polly A. Newcomb</name>
<name sortKey="Nickerson, Deborah A" sort="Nickerson, Deborah A" uniqKey="Nickerson D" first="Deborah A." last="Nickerson">Deborah A. Nickerson</name>
<name sortKey="Peters, Ulrike" sort="Peters, Ulrike" uniqKey="Peters U" first="Ulrike" last="Peters">Ulrike Peters</name>
<name sortKey="Peters, Ulrike" sort="Peters, Ulrike" uniqKey="Peters U" first="Ulrike" last="Peters">Ulrike Peters</name>
<name sortKey="Potter, John D" sort="Potter, John D" uniqKey="Potter J" first="John D." last="Potter">John D. Potter</name>
<name sortKey="Potter, John D" sort="Potter, John D" uniqKey="Potter J" first="John D." last="Potter">John D. Potter</name>
<name sortKey="Schoen, Robert E" sort="Schoen, Robert E" uniqKey="Schoen R" first="Robert E." last="Schoen">Robert E. Schoen</name>
<name sortKey="Schumacher, Fredrick R" sort="Schumacher, Fredrick R" uniqKey="Schumacher F" first="Fredrick R." last="Schumacher">Fredrick R. Schumacher</name>
<name sortKey="Seminara, Daniela" sort="Seminara, Daniela" uniqKey="Seminara D" first="Daniela" last="Seminara">Daniela Seminara</name>
<name sortKey="Slattery, Martha L" sort="Slattery, Martha L" uniqKey="Slattery M" first="Martha L." last="Slattery">Martha L. Slattery</name>
<name sortKey="White, Emily" sort="White, Emily" uniqKey="White E" first="Emily" last="White">Emily White</name>
<name sortKey="White, Emily" sort="White, Emily" uniqKey="White E" first="Emily" last="White">Emily White</name>
</country>
<country name="France">
<region name="Pays de la Loire">
<name sortKey="Bezieau, Stephane" sort="Bezieau, Stephane" uniqKey="Bezieau S" first="Stephane" last="Bezieau">Stephane Bezieau</name>
</region>
<name sortKey="Kury, Sebastien" sort="Kury, Sebastien" uniqKey="Kury S" first="Sébastien" last="Küry">Sébastien Küry</name>
</country>
<country name="Allemagne">
<region name="Bade-Wurtemberg">
<name sortKey="Brenner, Hermann" sort="Brenner, Hermann" uniqKey="Brenner H" first="Hermann" last="Brenner">Hermann Brenner</name>
</region>
<name sortKey="Brenner, Hermann" sort="Brenner, Hermann" uniqKey="Brenner H" first="Hermann" last="Brenner">Hermann Brenner</name>
<name sortKey="Butterbach, Katja" sort="Butterbach, Katja" uniqKey="Butterbach K" first="Katja" last="Butterbach">Katja Butterbach</name>
<name sortKey="Chang Claude, Jenny" sort="Chang Claude, Jenny" uniqKey="Chang Claude J" first="Jenny" last="Chang-Claude">Jenny Chang-Claude</name>
<name sortKey="Hoffmeister, Michael" sort="Hoffmeister, Michael" uniqKey="Hoffmeister M" first="Michael" last="Hoffmeister">Michael Hoffmeister</name>
</country>
<country name="Canada">
<noRegion>
<name sortKey="Gallinger, Steven" sort="Gallinger, Steven" uniqKey="Gallinger S" first="Steven" last="Gallinger">Steven Gallinger</name>
</noRegion>
<name sortKey="Hudson, Thomas J" sort="Hudson, Thomas J" uniqKey="Hudson T" first="Thomas J." last="Hudson">Thomas J. Hudson</name>
<name sortKey="Hudson, Thomas J" sort="Hudson, Thomas J" uniqKey="Hudson T" first="Thomas J." last="Hudson">Thomas J. Hudson</name>
</country>
<country name="Australie">
<region name="Victoria (État)">
<name sortKey="Hopper, John L" sort="Hopper, John L" uniqKey="Hopper J" first="John L." last="Hopper">John L. Hopper</name>
</region>
<name sortKey="Jenkins, Mark A" sort="Jenkins, Mark A" uniqKey="Jenkins M" first="Mark A." last="Jenkins">Mark A. Jenkins</name>
</country>
<country name="Nouvelle-Zélande">
<noRegion>
<name sortKey="Potter, John D" sort="Potter, John D" uniqKey="Potter J" first="John D." last="Potter">John D. Potter</name>
</noRegion>
</country>
</tree>
</affiliations>
</record>

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