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

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 add... Full description

Journal Title: Du M., S. Jiao, S. A. Bien, M. Gala, G. Abecasis, S. Bezieau, H. Brenner, et al. 2016. “Fine-Mapping of Common Genetic Variants Associated with Colorectal Tumor Risk Identified Potential Functional Variants.” PLoS ONE 11 (7): e0157521. doi:10.1371/journal.pone.0157521. http://dx.doi.org/10.1371/journal.pone.0157521.
Main Author: Du, Mengmeng
Other Authors: Jiao, Shuo , Bien, Stephanie A. , Gala, Manish , Abecasis, Goncalo , Bezieau, Stephane , Brenner, Hermann , Butterbach, Katja , Caan, Bette J. , Carlson, Christopher S. , Casey, Graham , Chang-Claude, Jenny , Conti, David V. , Curtis, Keith R. , Duggan, David , Gallinger, Steven , Haile, Robert W. , Harrison, Tabitha A. , Hayes, Richard B. , Hoffmeister, Michael , Hopper, John L. , Hudson, Thomas J. , Jenkins, Mark A. , Küry, Sébastien , Le Marchand, Loic , Leal, Suzanne M. , Newcomb, Polly A. , Nickerson, Deborah A. , Potter, John D. , Schoen, Robert E. , Schumacher, Fredrick R. , Seminara, Daniela , Slattery, Martha L. , Hsu, Li , Chan, Andrew T. , White, Emily , Berndt, Sonja I. , Peters, Ulrike
Format: Electronic Article Electronic Article
Language: English
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ID: ISSN: 1932-6203 ; DOI: 10.1371/journal.pone.0157521
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title: Fine-Mapping of Common Genetic Variants Associated with Colorectal Tumor Risk Identified Potential Functional Variants
format: Article
creator:
  • Du, Mengmeng
  • Jiao, Shuo
  • Bien, Stephanie A.
  • Gala, Manish
  • Abecasis, Goncalo
  • Bezieau, Stephane
  • Brenner, Hermann
  • Butterbach, Katja
  • Caan, Bette J.
  • Carlson, Christopher S.
  • Casey, Graham
  • Chang-Claude, Jenny
  • Conti, David V.
  • Curtis, Keith R.
  • Duggan, David
  • Gallinger, Steven
  • Haile, Robert W.
  • Harrison, Tabitha A.
  • Hayes, Richard B.
  • Hoffmeister, Michael
  • Hopper, John L.
  • Hudson, Thomas J.
  • Jenkins, Mark A.
  • Küry, Sébastien
  • Le Marchand, Loic
  • Leal, Suzanne M.
  • Newcomb, Polly A.
  • Nickerson, Deborah A.
  • Potter, John D.
  • Schoen, Robert E.
  • Schumacher, Fredrick R.
  • Seminara, Daniela
  • Slattery, Martha L.
  • Hsu, Li
  • Chan, Andrew T.
  • White, Emily
  • Berndt, Sonja I.
  • Peters, Ulrike
subjects:
  • Medicine And Health Sciences
  • Oncology
  • Cancers And Neoplasms
  • Colorectal Cancer
  • Biology And Life Sciences
  • Computational Biology
  • Genome Analysis
  • Genome-Wide Association Studies
  • Genetics
  • Genomics
  • Human Genetics
  • Database And Informatics Methods
  • Biological Databases
  • Genomic Databases
  • Functional Genomics
  • Cell Biology
  • Signal Transduction
  • Cell Signaling
  • Genomic Signal Processing
  • Genetic Loci
  • Bioinformatics
  • Alleles
ispartof: Du, M., S. Jiao, S. A. Bien, M. Gala, G. Abecasis, S. Bezieau, H. Brenner, et al. 2016. “Fine-Mapping of Common Genetic Variants Associated with Colorectal Tumor Risk Identified Potential Functional Variants.” PLoS ONE 11 (7): e0157521. doi:10.1371/journal.pone.0157521. http://dx.doi.org/10.1371/journal.pone.0157521.
description: 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).
language: eng
source:
identifier: ISSN: 1932-6203 ; DOI: 10.1371/journal.pone.0157521
fulltext: fulltext_linktorsrc
issn:
  • 1932-6203
  • 19326203
url: Link


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titleFine-Mapping of Common Genetic Variants Associated with Colorectal Tumor Risk Identified Potential Functional Variants
creatorDu, Mengmeng ; Jiao, Shuo ; Bien, Stephanie A. ; Gala, Manish ; Abecasis, Goncalo ; Bezieau, Stephane ; Brenner, Hermann ; Butterbach, Katja ; Caan, Bette J. ; Carlson, Christopher S. ; Casey, Graham ; Chang-Claude, Jenny ; Conti, David V. ; Curtis, Keith R. ; Duggan, David ; Gallinger, Steven ; Haile, Robert W. ; Harrison, Tabitha A. ; Hayes, Richard B. ; Hoffmeister, Michael ; Hopper, John L. ; Hudson, Thomas J. ; Jenkins, Mark A. ; Küry, Sébastien ; Le Marchand, Loic ; Leal, Suzanne M. ; Newcomb, Polly A. ; Nickerson, Deborah A. ; Potter, John D. ; Schoen, Robert E. ; Schumacher, Fredrick R. ; Seminara, Daniela ; Slattery, Martha L. ; Hsu, Li ; Chan, Andrew T. ; White, Emily ; Berndt, Sonja I. ; Peters, Ulrike
ispartofDu, M., S. Jiao, S. A. Bien, M. Gala, G. Abecasis, S. Bezieau, H. Brenner, et al. 2016. “Fine-Mapping of Common Genetic Variants Associated with Colorectal Tumor Risk Identified Potential Functional Variants.” PLoS ONE 11 (7): e0157521. doi:10.1371/journal.pone.0157521. http://dx.doi.org/10.1371/journal.pone.0157521.
identifierISSN: 1932-6203 ; DOI: 10.1371/journal.pone.0157521
subjectMedicine And Health Sciences ; Oncology ; Cancers And Neoplasms ; Colorectal Cancer ; Biology And Life Sciences ; Computational Biology ; Genome Analysis ; Genome-Wide Association Studies ; Genetics ; Genomics ; Human Genetics ; Database And Informatics Methods ; Biological Databases ; Genomic Databases ; Functional Genomics ; Cell Biology ; Signal Transduction ; Cell Signaling ; Genomic Signal Processing ; Genetic Loci ; Bioinformatics ; Alleles
descriptionGenome-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).
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21Hudson, Thomas J.
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23Küry, Sébastien
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27Nickerson, Deborah A.
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29Schoen, Robert E.
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33Hsu, Li
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36Berndt, Sonja I.
37Peters, Ulrike
titleFine-Mapping of Common Genetic Variants Associated with Colorectal Tumor Risk Identified Potential Functional Variants
descriptionGenome-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).
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1Oncology
2Cancers and Neoplasms
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4Biology and Life Sciences
5Computational Biology
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7Genome-Wide Association Studies
8Genetics
9Genomics
10Human Genetics
11Database and Informatics Methods
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titleFine-Mapping of Common Genetic Variants Associated with Colorectal Tumor Risk Identified Potential Functional Variants
authorDu, Mengmeng ; Jiao, Shuo ; Bien, Stephanie A. ; Gala, Manish ; Abecasis, Goncalo ; Bezieau, Stephane ; Brenner, Hermann ; Butterbach, Katja ; Caan, Bette J. ; Carlson, Christopher S. ; Casey, Graham ; Chang-Claude, Jenny ; Conti, David V. ; Curtis, Keith R. ; Duggan, David ; Gallinger, Steven ; Haile, Robert W. ; Harrison, Tabitha A. ; Hayes, Richard B. ; Hoffmeister, Michael ; Hopper, John L. ; Hudson, Thomas J. ; Jenkins, Mark A. ; Küry, Sébastien ; Le Marchand, Loic ; Leal, Suzanne M. ; Newcomb, Polly A. ; Nickerson, Deborah A. ; Potter, John D. ; Schoen, Robert E. ; Schumacher, Fredrick R. ; Seminara, Daniela ; Slattery, Martha L. ; Hsu, Li ; Chan, Andrew T. ; White, Emily ; Berndt, Sonja I. ; Peters, Ulrike
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15Cell Biology
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9Carlson, Christopher S
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29Schoen, Robert E
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34Chan, Andrew T
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atitleFine-Mapping of Common Genetic Variants Associated with Colorectal Tumor Risk Identified Potential Functional Variants
jtitlePLoS ONE
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abstractGenome-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).
pubPublic Library of Science
doi10.1371/journal.pone.0157521
urlhttp://www.ncbi.nlm.nih.gov/pmc/articles/PMC4933364/pdf/
volume11
pagese0157521
issue7
oafree_for_read