IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v9y2018i1d10.1038_s41467-018-06705-0.html
   My bibliography  Save this article

A missense variant in SLC39A8 is associated with severe idiopathic scoliosis

Author

Listed:
  • Gabe Haller

    (Washington University)

  • Kevin McCall

    (Washington University)

  • Supak Jenkitkasemwong

    (University of Florida)

  • Brooke Sadler

    (Washington University)

  • Lilian Antunes

    (Washington University)

  • Momchil Nikolov

    (Washington University)

  • Julia Whittle

    (Washington University)

  • Zachary Upshaw

    (Washington University)

  • Jimann Shin

    (Washington University School of Medicine)

  • Erin Baschal

    (University of Colorado)

  • Carlos Cruchaga

    (Washington University)

  • Matthew Harms

    (Columbia University)

  • Cathleen Raggio

    (Hospital for Special Surgery)

  • Jose A. Morcuende

    (University of Iowa)

  • Philip Giampietro

    (Drexel University)

  • Nancy H. Miller

    (University of Colorado)

  • Carol Wise

    (Texas Scottish Rite Hospital for Children
    University of Texas Southwestern Medical Center at Dallas
    University of Texas Southwestern Medical Center at Dallas)

  • Ryan S. Gray

    (The University of Texas at Austin)

  • Lila Solnica-Krezel

    (Washington University School of Medicine)

  • Mitchell Knutson

    (University of Florida)

  • Matthew B. Dobbs

    (Washington University
    Shriners Hospital for Children)

  • Christina A. Gurnett

    (Washington University
    Washington University
    Washington University)

Abstract

Genetic factors predictive of severe adolescent idiopathic scoliosis (AIS) are largely unknown. To identify genetic variation associated with severe AIS, we performed an exome-wide association study of 457 severe AIS cases and 987 controls. We find a missense SNP in SLC39A8 (p.Ala391Thr, rs13107325) associated with severe AIS (P = 1.60 × 10−7, OR = 2.01, CI = 1.54–2.62). This pleiotropic SNP was previously associated with BMI, blood pressure, cholesterol, and blood manganese level. We replicate the association in a second cohort (841 cases and 1095 controls) resulting in a combined P = 7.02 × 10−14, OR = 1.94, CI = 1.63–2.34. Clinically, the minor allele of rs13107325 is associated with greater spinal curvature, decreased height, increased BMI and lower plasma manganese in our AIS cohort. Functional studies demonstrate reduced manganese influx mediated by the SLC39A8 p.Ala391Thr variant and vertebral abnormalities, impaired growth, and decreased motor activity in slc39a8 mutant zebrafish. Our results suggest the possibility that scoliosis may be amenable to dietary intervention.

Suggested Citation

  • Gabe Haller & Kevin McCall & Supak Jenkitkasemwong & Brooke Sadler & Lilian Antunes & Momchil Nikolov & Julia Whittle & Zachary Upshaw & Jimann Shin & Erin Baschal & Carlos Cruchaga & Matthew Harms & , 2018. "A missense variant in SLC39A8 is associated with severe idiopathic scoliosis," Nature Communications, Nature, vol. 9(1), pages 1-7, December.
    • Handle: RePEc:nat:natcom:v:9:y:2018:i:1:d:10.1038_s41467-018-06705-0
    DOI: 10.1038/s41467-018-06705-0
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-018-06705-0
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/s41467-018-06705-0?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
    ---><---

    Citations

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


    Cited by:

    1. Liina Nagirnaja & Alexandra M. Lopes & Wu-Lin Charng & Brian Miller & Rytis Stakaitis & Ieva Golubickaite & Alexandra Stendahl & Tianpengcheng Luan & Corinna Friedrich & Eisa Mahyari & Eloise Fadial &, 2022. "Diverse monogenic subforms of human spermatogenic failure," Nature Communications, Nature, vol. 13(1), pages 1-18, December.
    2. Gianmarco Mignogna & Caitlin E. Carey & Robbee Wedow & Nikolas Baya & Mattia Cordioli & Nicola Pirastu & Rino Bellocco & Kathryn Fiuza Malerbi & Michel G. Nivard & Benjamin M. Neale & Raymond K. Walte, 2023. "Patterns of item nonresponse behaviour to survey questionnaires are systematic and associated with genetic loci," Nature Human Behaviour, Nature, vol. 7(8), pages 1371-1387, August.

    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:nat:natcom:v:9:y:2018:i:1:d:10.1038_s41467-018-06705-0. 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: Sonal Shukla or Springer Nature Abstracting and Indexing (email available below). General contact details of provider: http://www.nature.com .

    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.