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Large-scale GWAS of strabismus identifies risk loci and provides support for a link with maternal smoking

Author

Listed:
  • Weixiong He

    (QIMR Berghofer Medical Research Institute
    University of Queensland)

  • Peter J. Most

    (University of Groningen)

  • Jue-Sheng Ong

    (QIMR Berghofer Medical Research Institute)

  • Liang-Dar Hwang

    (University of Queensland)

  • Yeda Wu

    (QIMR Berghofer Medical Research Institute)

  • Morten S. Magnø

    (University of Groningen
    Sørlandet Hospital Arendal
    Oslo University Hospital)

  • Jelle Vehof

    (King’s College London
    University of Groningen
    Vestfold Hospital Trust)

  • Kristi Krebs

    (University of Tartu)

  • Laura Mauring

    (Tartu University Hospital
    University of Tartu
    Tartu University Hospital)

  • Katrin Õunap

    (Tartu University Hospital
    University of Tartu)

  • Erik Abner

    (University of Tartu)

  • Nicholas G. Martin

    (QIMR Berghofer Medical Research Institute)

  • Denis Plotnikov

    (Kazan State Medical University)

  • Chen Jiang

    (Kaiser Permanente Northern California)

  • Ronald B. Melles

    (Kaiser Permanente Northern California)

  • Puya Gharahkhani

    (QIMR Berghofer Medical Research Institute
    University of Queensland)

  • Harold Snieder

    (University of Groningen)

  • Teele Palumaa

    (University of Tartu
    East Tallinn Central Hospital)

  • Kuldar Kaljurand

    (Tartu University Hospital
    University of Tartu)

  • Jeremy A. Guggenheim

    (Cardiff University)

  • David A. Mackey

    (University of Western Australia)

  • Elizabeth C. Engle

    (Boston Children’s Hospital and Harvard Medical School
    Boston Children’s Hospital and Harvard Medical School
    Howard Hughes Medical Institute)

  • Hélène Choquet

    (Kaiser Permanente Northern California)

  • Stuart MacGregor

    (QIMR Berghofer Medical Research Institute
    University of Queensland)

Abstract

Strabismus is a common pediatric eye misalignment and has complex genetic and environmental causes. Previous genome-wide association studies (GWAS) encountered difficulties in identifying strabismus risk variants due to heterogeneity and small samples. We performed large meta-analyses of 11 European-ancestry GWAS (7 sources), analysing broad strabismus (20,464 cases, 954,921 controls) and subtypes (esotropia/exotropia). We discovered 4 loci (e.g., NPLOC4-TSPAN10-PDE6G-FAAP100, COL6A1) for strabismus and 5 additional loci (e.g., CHRNA4, MAD1L1) for strabismus subtypes and we successfully replicated the previously reported strabismus variant near NPLOC4-TSPAN10-PDE6G-FAAP100. Using mendelian randomisation, we found genetic evidence supporting maternal smoking as a causal risk factor for strabismus in offspring.

Suggested Citation

  • Weixiong He & Peter J. Most & Jue-Sheng Ong & Liang-Dar Hwang & Yeda Wu & Morten S. Magnø & Jelle Vehof & Kristi Krebs & Laura Mauring & Katrin Õunap & Erik Abner & Nicholas G. Martin & Denis Plotniko, 2025. "Large-scale GWAS of strabismus identifies risk loci and provides support for a link with maternal smoking," Nature Communications, Nature, vol. 16(1), pages 1-14, December.
    • Handle: RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-62456-9
    DOI: 10.1038/s41467-025-62456-9
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    1. Clare Bycroft & Colin Freeman & Desislava Petkova & Gavin Band & Lloyd T. Elliott & Kevin Sharp & Allan Motyer & Damjan Vukcevic & Olivier Delaneau & Jared O’Connell & Adrian Cortes & Samantha Welsh &, 2018. "The UK Biobank resource with deep phenotyping and genomic data," Nature, Nature, vol. 562(7726), pages 203-209, October.
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