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Cross-ethnic meta-analysis identifies association of the GPX3-TNIP1 locus with amyotrophic lateral sclerosis

Author

Listed:
  • Beben Benyamin

    (The University of Queensland
    The University of Queensland)

  • Ji He

    (Peking University, Third Hospital)

  • Qiongyi Zhao

    (The University of Queensland)

  • Jacob Gratten

    (The University of Queensland
    The University of Queensland)

  • Fleur Garton

    (The University of Queensland
    The University of Queensland)

  • Paul J. Leo

    (University of Queensland Diamantina Institute, The University of Queensland, Translational Research Institute
    Queensland University of Technology, Translational Research Institute)

  • Zhijun Liu

    (The University of Queensland
    The University of Queensland)

  • Marie Mangelsdorf

    (The University of Queensland)

  • Ammar Al-Chalabi

    (King’s College London)

  • Lisa Anderson

    (University of Queensland Diamantina Institute, The University of Queensland, Translational Research Institute
    Queensland University of Technology, Translational Research Institute)

  • Timothy J. Butler

    (The University of Queensland)

  • Lu Chen

    (Peking University, Third Hospital)

  • Xiang-Ding Chen

    (Hunan Normal University)

  • Katie Cremin

    (University of Queensland Diamantina Institute, The University of Queensland, Translational Research Institute
    Queensland University of Technology, Translational Research Institute)

  • Hong-Weng Deng

    (Tulane University)

  • Matthew Devine

    (Royal Brisbane & Women’s Hospital)

  • Janette Edson

    (The University of Queensland)

  • Jennifer A. Fifita

    (Macquarie University)

  • Sarah Furlong

    (The University of Queensland)

  • Ying-Ying Han

    (University of Shanghai for Science and Technology)

  • Jessica Harris

    (University of Queensland Diamantina Institute, The University of Queensland, Translational Research Institute
    Queensland University of Technology, Translational Research Institute)

  • Anjali K. Henders

    (The University of Queensland
    The University of Queensland)

  • Rosalind L. Jeffree

    (Royal Brisbane & Women’s Hospital)

  • Zi-Bing Jin

    (The Eye Hospital of Wenzhou Medical University)

  • Zhongshan Li

    (Wenzhou Medical University)

  • Ting Li

    (The Second Military Medical University)

  • Mengmeng Li

    (The Second Military Medical University)

  • Yong Lin

    (University of Shanghai for Science and Technology)

  • Xiaolu Liu

    (Peking University, Third Hospital)

  • Mhairi Marshall

    (University of Queensland Diamantina Institute, The University of Queensland, Translational Research Institute
    Queensland University of Technology, Translational Research Institute)

  • Emily P. McCann

    (Macquarie University)

  • Bryan J. Mowry

    (The University of Queensland)

  • Shyuan T. Ngo

    (The University of Queensland
    The University of Queensland)

  • Roger Pamphlett

    (The University of Sydney)

  • Shu Ran

    (University of Shanghai for Science and Technology)

  • David C. Reutens

    (The University of Queensland)

  • Dominic B. Rowe

    (Macquarie University)

  • Perminder Sachdev

    (The University of New South Wales
    Prince of Wales Hospital)

  • Sonia Shah

    (The University of Queensland)

  • Sharon Song

    (University of Queensland Diamantina Institute, The University of Queensland, Translational Research Institute
    Queensland University of Technology, Translational Research Institute)

  • Li-Jun Tan

    (Hunan Normal University)

  • Lu Tang

    (Peking University, Third Hospital)

  • Leonard H. Berg

    (University Medical Center Utrecht)

  • Wouter Rheenen

    (University Medical Center Utrecht)

  • Jan H. Veldink

    (University Medical Center Utrecht)

  • Robyn H. Wallace

    (The University of Queensland)

  • Lawrie Wheeler

    (University of Queensland Diamantina Institute, The University of Queensland, Translational Research Institute
    Queensland University of Technology, Translational Research Institute)

  • Kelly L. Williams

    (Macquarie University)

  • Jinyu Wu

    (Wenzhou Medical University)

  • Xin Wu

    (The Second Military Medical University)

  • Jian Yang

    (The University of Queensland
    The University of Queensland)

  • Weihua Yue

    (Peking University
    Peking University)

  • Zong-Hong Zhang

    (The University of Queensland)

  • Dai Zhang

    (Peking University
    Peking University)

  • Peter G. Noakes

    (Royal Brisbane & Women’s Hospital)

  • Ian P. Blair

    (Macquarie University)

  • Robert D. Henderson

    (The University of Queensland
    Royal Brisbane & Women’s Hospital)

  • Pamela A. McCombe

    (Royal Brisbane & Women’s Hospital
    The University of Queensland, Royal Brisbane & Women’s Hospital)

  • Peter M. Visscher

    (The University of Queensland
    The University of Queensland)

  • Huji Xu

    (The Second Military Medical University)

  • Perry F. Bartlett

    (The University of Queensland)

  • Matthew A. Brown

    (University of Queensland Diamantina Institute, The University of Queensland, Translational Research Institute
    Queensland University of Technology, Translational Research Institute)

  • Naomi R. Wray

    (The University of Queensland
    The University of Queensland)

  • Dongsheng Fan

    (Peking University, Third Hospital)

Abstract

Cross-ethnic genetic studies can leverage power from differences in disease epidemiology and population-specific genetic architecture. In particular, the differences in linkage disequilibrium and allele frequency patterns across ethnic groups may increase gene-mapping resolution. Here we use cross-ethnic genetic data in sporadic amyotrophic lateral sclerosis (ALS), an adult-onset, rapidly progressing neurodegenerative disease. We report analyses of novel genome-wide association study data of 1,234 ALS cases and 2,850 controls. We find a significant association of rs10463311 spanning GPX3-TNIP1 with ALS (p = 1.3 × 10−8), with replication support from two independent Australian samples (combined 576 cases and 683 controls, p = 1.7 × 10−3). Both GPX3 and TNIP1 interact with other known ALS genes (SOD1 and OPTN, respectively). In addition, GGNBP2 was identified using gene-based analysis and summary statistics-based Mendelian randomization analysis, although further replication is needed to confirm this result. Our results increase our understanding of genetic aetiology of ALS.

Suggested Citation

  • Beben Benyamin & Ji He & Qiongyi Zhao & Jacob Gratten & Fleur Garton & Paul J. Leo & Zhijun Liu & Marie Mangelsdorf & Ammar Al-Chalabi & Lisa Anderson & Timothy J. Butler & Lu Chen & Xiang-Ding Chen &, 2017. "Cross-ethnic meta-analysis identifies association of the GPX3-TNIP1 locus with amyotrophic lateral sclerosis," Nature Communications, Nature, vol. 8(1), pages 1-7, December.
    • Handle: RePEc:nat:natcom:v:8:y:2017:i:1:d:10.1038_s41467-017-00471-1
    DOI: 10.1038/s41467-017-00471-1
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