IDEAS home Printed from https://ideas.repec.org/a/plo/pone00/0101178.html
   My bibliography  Save this article

A Colorectal Cancer Susceptibility New Variant at 4q26 in the Spanish Population Identified by Genome-Wide Association Analysis

Author

Listed:
  • Luis M Real
  • Agustín Ruiz
  • Javier Gayán
  • Antonio González-Pérez
  • María E Sáez
  • Reposo Ramírez-Lorca
  • Francisco J Morón
  • Juan Velasco
  • Ruth Marginet-Flinch
  • Eva Musulén
  • José M Carrasco
  • Concha Moreno-Rey
  • Enrique Vázquez
  • Manuel Chaves-Conde
  • Jose A Moreno-Nogueira
  • Manuel Hidalgo-Pascual
  • Eduardo Ferrero-Herrero
  • Sergi Castellví-Bel
  • Antoni Castells
  • Ceres Fernandez-Rozadilla
  • Clara Ruiz-Ponte
  • Angel Carracedo
  • Beatriz González
  • Sergio Alonso
  • Manuel Perucho

Abstract

Background: Non-hereditary colorectal cancer (CRC) is a complex disorder resulting from the combination of genetic and non-genetic factors. Genome–wide association studies (GWAS) are useful for identifying such genetic susceptibility factors. However, the single loci so far associated with CRC only represent a fraction of the genetic risk for CRC development in the general population. Therefore, many other genetic risk variants alone and in combination must still remain to be discovered. The aim of this work was to search for genetic risk factors for CRC, by performing single-locus and two-locus GWAS in the Spanish population. Results: A total of 801 controls and 500 CRC cases were included in the discovery GWAS dataset. 77 single nucleotide polymorphisms (SNP)s from single-locus and 243 SNPs from two-locus association analyses were selected for replication in 423 additional CRC cases and 1382 controls. In the meta-analysis, one SNP, rs3987 at 4q26, reached GWAS significant p-value (p = 4.02×10−8), and one SNP pair, rs1100508 CG and rs8111948 AA, showed a trend for two-locus association (p = 4.35×10−11). Additionally, our GWAS confirmed the previously reported association with CRC of five SNPs located at 3q36.2 (rs10936599), 8q24 (rs10505477), 8q24.21(rs6983267), 11q13.4 (rs3824999) and 14q22.2 (rs4444235). Conclusions: Our GWAS for CRC patients from Spain confirmed some previously reported associations for CRC and yielded a novel candidate risk SNP, located at 4q26. Epistasis analyses also yielded several novel candidate susceptibility pairs that need to be validated in independent analyses.

Suggested Citation

  • Luis M Real & Agustín Ruiz & Javier Gayán & Antonio González-Pérez & María E Sáez & Reposo Ramírez-Lorca & Francisco J Morón & Juan Velasco & Ruth Marginet-Flinch & Eva Musulén & José M Carrasco & Con, 2014. "A Colorectal Cancer Susceptibility New Variant at 4q26 in the Spanish Population Identified by Genome-Wide Association Analysis," PLOS ONE, Public Library of Science, vol. 9(6), pages 1-11, June.
    • Handle: RePEc:plo:pone00:0101178
    DOI: 10.1371/journal.pone.0101178
    as

    Download full text from publisher

    File URL: https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0101178
    Download Restriction: no
    File URL: https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0101178&type=printable
    Download Restriction: no
    File URL: https://libkey.io/10.1371/journal.pone.0101178?utm_source=ideas
    LibKey link: if access is restricted and if your library uses this service, LibKey will redirect you to where you can use your library subscription to access this item
    ---><---

    References listed on IDEAS

    as
    1. Nick Patterson & Alkes L Price & David Reich, 2006. "Population Structure and Eigenanalysis," PLOS Genetics, Public Library of Science, vol. 2(12), pages 1-20, December.
    2. Shuo Jiao & Li Hsu & Sonja Berndt & Stéphane Bézieau & Hermann Brenner & Daniel Buchanan & Bette J Caan & Peter T Campbell & Christopher S Carlson & Graham Casey & Andrew T Chan & Jenny Chang-Claude &, 2012. "Genome-Wide Search for Gene-Gene Interactions in Colorectal Cancer," PLOS ONE, Public Library of Science, vol. 7(12), pages 1-14, December.
    3. Gregory S Barsh & Gregory P Copenhaver & Greg Gibson & Scott M Williams, 2012. "Guidelines for Genome-Wide Association Studies," PLOS Genetics, Public Library of Science, vol. 8(7), pages 1-2, July.
    Full references (including those not matched with items on IDEAS)

    Most related items

    These are the items that most often cite the same works as this one and are cited by the same works as this one.
    1. Gyaneshwer Chaubey & Anurag Kadian & Saroj Bala & Vadlamudi Raghavendra Rao, 2015. "Genetic Affinity of the Bhil, Kol and Gond Mentioned in Epic Ramayana," PLOS ONE, Public Library of Science, vol. 10(6), pages 1-11, June.
    2. Daniel Svensson & Matilda Rentoft & Anna M Dahlin & Emma Lundholm & Pall I Olason & Andreas Sjödin & Carin Nylander & Beatrice S Melin & Johan Trygg & Erik Johansson, 2020. "A whole-genome sequenced control population in northern Sweden reveals subregional genetic differences," PLOS ONE, Public Library of Science, vol. 15(9), pages 1-18, September.
    3. Estavoyer, Maxime & François, Olivier, 2022. "Theoretical analysis of principal components in an umbrella model of intraspecific evolution," Theoretical Population Biology, Elsevier, vol. 148(C), pages 11-21.
    4. Felsenstein, Joseph, 2015. "Covariation of gene frequencies in a stepping-stone lattice of populations," Theoretical Population Biology, Elsevier, vol. 100(C), pages 88-97.
    5. Yaron Granot & Omri Tal & Saharon Rosset & Karl Skorecki, 2016. "On the Apportionment of Population Structure," PLOS ONE, Public Library of Science, vol. 11(8), pages 1-24, August.
    6. Özkan İş & Xue Wang & Joseph S. Reddy & Yuhao Min & Elanur Yilmaz & Prabesh Bhattarai & Tulsi Patel & Jeremiah Bergman & Zachary Quicksall & Michael G. Heckman & Frederick Q. Tutor-New & Birsen Can De, 2024. "Gliovascular transcriptional perturbations in Alzheimer’s disease reveal molecular mechanisms of blood brain barrier dysfunction," Nature Communications, Nature, vol. 15(1), pages 1-23, December.
    7. Hyosik Jang & Ian M Ehrenreich, 2012. "Genome-Wide Characterization of Genetic Variation in the Unicellular, Green Alga Chlamydomonas reinhardtii," PLOS ONE, Public Library of Science, vol. 7(7), pages 1-9, July.
    8. Mathieu Gautier & Denis Laloë & Katayoun Moazami-Goudarzi, 2010. "Insights into the Genetic History of French Cattle from Dense SNP Data on 47 Worldwide Breeds," PLOS ONE, Public Library of Science, vol. 5(9), pages 1-11, September.
    9. Xiaofeng Cai & Xuepeng Sun & Chenxi Xu & Honghe Sun & Xiaoli Wang & Chenhui Ge & Zhonghua Zhang & Quanxi Wang & Zhangjun Fei & Chen Jiao & Quanhua Wang, 2021. "Genomic analyses provide insights into spinach domestication and the genetic basis of agronomic traits," Nature Communications, Nature, vol. 12(1), pages 1-12, December.
    10. Lee, Anthony J. & Hibbs, Courtney & Wright, Margaret J. & Martin, Nicholas G. & Keller, Matthew C. & Zietsch, Brendan P., 2017. "Assessing the accuracy of perceptions of intelligence based on heritable facial features," Intelligence, Elsevier, vol. 64(C), pages 1-8.
    11. Thompson Katherine L. & Linnen Catherine R. & Kubatko Laura, 2016. "Tree-based quantitative trait mapping in the presence of external covariates," Statistical Applications in Genetics and Molecular Biology, De Gruyter, vol. 15(6), pages 473-490, December.
    12. Matthieu Bouaziz & Caroline Paccard & Mickael Guedj & Christophe Ambroise, 2012. "SHIPS: Spectral Hierarchical Clustering for the Inference of Population Structure in Genetic Studies," PLOS ONE, Public Library of Science, vol. 7(10), pages 1-17, October.
    13. Jacobo Pardo-Seco & Alberto Gómez-Carballa & Jorge Amigo & Federico Martinón-Torres & Antonio Salas, 2014. "A Genome-Wide Study of Modern-Day Tuscans: Revisiting Herodotus's Theory on the Origin of the Etruscans," PLOS ONE, Public Library of Science, vol. 9(9), pages 1-11, September.
    14. Andrey V Khrunin & Denis V Khokhrin & Irina N Filippova & Tõnu Esko & Mari Nelis & Natalia A Bebyakova & Natalia L Bolotova & Janis Klovins & Liene Nikitina-Zake & Karola Rehnström & Samuli Ripatti & , 2013. "A Genome-Wide Analysis of Populations from European Russia Reveals a New Pole of Genetic Diversity in Northern Europe," PLOS ONE, Public Library of Science, vol. 8(3), pages 1-9, March.
    15. Ilja M Nolte & Chris Wallace & Stephen J Newhouse & Daryl Waggott & Jingyuan Fu & Nicole Soranzo & Rhian Gwilliam & Panos Deloukas & Irina Savelieva & Dongling Zheng & Chrysoula Dalageorgou & Martin F, 2009. "Common Genetic Variation Near the Phospholamban Gene Is Associated with Cardiac Repolarisation: Meta-Analysis of Three Genome-Wide Association Studies," PLOS ONE, Public Library of Science, vol. 4(7), pages 1-10, July.
    16. Hoicheong Siu & Li Jin & Momiao Xiong, 2012. "Manifold Learning for Human Population Structure Studies," PLOS ONE, Public Library of Science, vol. 7(1), pages 1-18, January.
    17. Elodie Persyn & Richard Redon & Lise Bellanger & Christian Dina, 2018. "The impact of a fine-scale population stratification on rare variant association test results," PLOS ONE, Public Library of Science, vol. 13(12), pages 1-17, December.
    18. Andre Krumel Portella & Afroditi Papantoni & Catherine Paquet & Spencer Moore & Keri Shiels Rosch & Stewart Mostofsky & Richard S Lee & Kimberly R Smith & Robert Levitan & Patricia Pelufo Silveira & S, 2020. "Predicted DRD4 prefrontal gene expression moderates snack intake and stress perception in response to the environment in adolescents," PLOS ONE, Public Library of Science, vol. 15(6), pages 1-20, June.
    19. Lindsay Fernández-Rhodes & Jennifer R Malinowski & Yujie Wang & Ran Tao & Nathan Pankratz & Janina M Jeff & Sachiko Yoneyama & Cara L Carty & V Wendy Setiawan & Loic Le Marchand & Christopher Haiman &, 2018. "The genetic underpinnings of variation in ages at menarche and natural menopause among women from the multi-ethnic Population Architecture using Genomics and Epidemiology (PAGE) Study: A trans-ethnic ," PLOS ONE, Public Library of Science, vol. 13(7), pages 1-21, July.
    20. Pierre Luisi & Angelina García & Juan Manuel Berros & Josefina M B Motti & Darío A Demarchi & Emma Alfaro & Eliana Aquilano & Carina Argüelles & Sergio Avena & Graciela Bailliet & Julieta Beltramo & C, 2020. "Fine-scale genomic analyses of admixed individuals reveal unrecognized genetic ancestry components in Argentina," PLOS ONE, Public Library of Science, vol. 15(7), pages 1-30, July.

    More about this item

    Statistics

    Access and download statistics

    Corrections

    All material on this site has been provided by the respective publishers and authors. You can help correct errors and omissions. When requesting a correction, please mention this item's handle: RePEc:plo:pone00:0101178. See general information about how to correct material in RePEc.

    If you have authored this item and are not yet registered with RePEc, we encourage you to do it here. This allows to link your profile to this item. It also allows you to accept potential citations to this item that we are uncertain about.

    If CitEc recognized a bibliographic reference but did not link an item in RePEc to it, you can help with this form .

    If you know of missing items citing this one, you can help us creating those links by adding the relevant references in the same way as above, for each refering item. If you are a registered author of this item, you may also want to check the "citations" tab in your RePEc Author Service profile, as there may be some citations waiting for confirmation.

    For technical questions regarding this item, or to correct its authors, title, abstract, bibliographic or download information, contact: plosone (email available below). General contact details of provider: https://journals.plos.org/plosone/ .

    Please note that corrections may take a couple of weeks to filter through the various RePEc services.

    IDEAS is a RePEc service. RePEc uses bibliographic data supplied by the respective publishers.