IDEAS home Printed from https://ideas.repec.org/a/plo/pone00/0115614.html
   My bibliography  Save this article

The Effect of Inversion at 8p23 on BLK Association with Lupus in Caucasian Population

Author

Listed:
  • Bahram Namjou
  • Yizhao Ni
  • Isaac T W Harley
  • Iouri Chepelev
  • Beth Cobb
  • Leah C Kottyan
  • Patrick M Gaffney
  • Joel M Guthridge
  • Kenneth Kaufman
  • John B Harley

Abstract

To explore the potential influence of the polymorphic 8p23.1 inversion on known autoimmune susceptibility risk at or near BLK locus, we validated a new bioinformatics method that utilizes SNP data to enable accurate, high-throughput genotyping of the 8p23.1 inversion in a Caucasian population. Methods: Principal components analysis (PCA) was performed using markers inside the inversion territory followed by k-means cluster analyses on 7416 European derived and 267 HapMaP CEU and TSI samples. A logistic regression conditional analysis was performed. Results: Three subgroups have been identified; inversion homozygous, heterozygous and non-inversion homozygous. The status of inversion was further validated using HapMap samples that had previously undergone Fluorescence in situ hybridization (FISH) assays with a concordance rate of above 98%. Conditional analyses based on the status of inversion were performed. We found that overall association signals in the BLK region remain significant after controlling for inversion status. The proportion of lupus cases and controls (cases/controls) in each subgroup was determined to be 0.97 for the inverted homozygous group (1067 cases and 1095 controls), 1.12 for the inverted heterozygous group (1935 cases 1717 controls) and 1.36 for non-inverted subgroups (924 cases and 678 controls). After calculating the linkage disequilibrium between inversion status and lupus risk haplotype we found that the lupus risk haplotype tends to reside on non-inversion background. As a result, a new association effect between non-inversion status and lupus phenotype has been identified ((p = 8.18×10−7, OR = 1.18, 95%CI = 1.10–1.26). Conclusion: Our results demonstrate that both known lupus risk haplotype and inversion status act additively in the pathogenesis of lupus. Since inversion regulates expression of many genes in its territory, altered expression of other genes might also be involved in the development of lupus.

Suggested Citation

  • Bahram Namjou & Yizhao Ni & Isaac T W Harley & Iouri Chepelev & Beth Cobb & Leah C Kottyan & Patrick M Gaffney & Joel M Guthridge & Kenneth Kaufman & John B Harley, 2014. "The Effect of Inversion at 8p23 on BLK Association with Lupus in Caucasian Population," PLOS ONE, Public Library of Science, vol. 9(12), pages 1-13, December.
    • Handle: RePEc:plo:pone00:0115614
    DOI: 10.1371/journal.pone.0115614
    as

    Download full text from publisher

    File URL: https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0115614
    Download Restriction: no
    File URL: https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0115614&type=printable
    Download Restriction: no
    File URL: https://libkey.io/10.1371/journal.pone.0115614?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. Jianzhong Ma & Christopher I Amos, 2012. "Investigation of Inversion Polymorphisms in the Human Genome Using Principal Components Analysis," PLOS ONE, Public Library of Science, vol. 7(7), pages 1-12, July.
    Full references (including those not matched with items on IDEAS)

    Citations

    Citations are extracted by the CitEc Project, subscribe to its RSS feed for this item.
    as


    Cited by:

    1. Thomas Charlon & Manuel Martínez-Bueno & Lara Bossini-Castillo & F David Carmona & Alessandro Di Cara & Jérôme Wojcik & Sviatoslav Voloshynovskiy & Javier Martín & Marta E Alarcón-Riquelme, 2016. "Single Nucleotide Polymorphism Clustering in Systemic Autoimmune Diseases," PLOS ONE, Public Library of Science, vol. 11(8), pages 1-10, August.

    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. Ronald J Nowling & Krystal R Manke & Scott J Emrich, 2020. "Detecting inversions with PCA in the presence of population structure," PLOS ONE, Public Library of Science, vol. 15(10), pages 1-20, October.

    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:pone00:0115614. 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.