IDEAS home Printed from https://ideas.repec.org/a/plo/pone00/0070774.html
   My bibliography  Save this article

From Interaction to Co-Association —A Fisher r-To-z Transformation-Based Simple Statistic for Real World Genome-Wide Association Study

Author

Listed:
  • Zhongshang Yuan
  • Hong Liu
  • Xiaoshuai Zhang
  • Fangyu Li
  • Jinghua Zhao
  • Furen Zhang
  • Fuzhong Xue

Abstract

Currently, the genetic variants identified by genome wide association study (GWAS) generally only account for a small proportion of the total heritability for complex disease. One crucial reason is the underutilization of gene-gene joint effects commonly encountered in GWAS, which includes their main effects and co-association. However, gene-gene co-association is often customarily put into the framework of gene-gene interaction vaguely. From the causal graph perspective, we elucidate in detail the concept and rationality of gene-gene co-association as well as its relationship with traditional gene-gene interaction, and propose two Fisher r-to-z transformation-based simple statistics to detect it. Three series of simulations further highlight that gene-gene co-association refers to the extent to which the joint effects of two genes differs from the main effects, not only due to the traditional interaction under the nearly independent condition but the correlation between two genes. The proposed statistics are more powerful than logistic regression under various situations, cannot be affected by linkage disequilibrium and can have acceptable false positive rate as long as strictly following the reasonable GWAS data analysis roadmap. Furthermore, an application to gene pathway analysis associated with leprosy confirms in practice that our proposed gene-gene co-association concepts as well as the correspondingly proposed statistics are strongly in line with reality.

Suggested Citation

  • Zhongshang Yuan & Hong Liu & Xiaoshuai Zhang & Fangyu Li & Jinghua Zhao & Furen Zhang & Fuzhong Xue, 2013. "From Interaction to Co-Association —A Fisher r-To-z Transformation-Based Simple Statistic for Real World Genome-Wide Association Study," PLOS ONE, Public Library of Science, vol. 8(7), pages 1-8, July.
  • Handle: RePEc:plo:pone00:0070774
    DOI: 10.1371/journal.pone.0070774
    as

    Download full text from publisher

    File URL: https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0070774
    Download Restriction: no

    File URL: https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0070774&type=printable
    Download Restriction: no

    File URL: https://libkey.io/10.1371/journal.pone.0070774?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
    ---><---

    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:pone00:0070774. 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.

    We have no bibliographic references for this item. You can help adding them by using 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.