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Sequence variation at ANAPC1 accounts for 24% of the variability in corneal endothelial cell density

Author

Listed:
  • Erna V. Ivarsdottir

    (deCODE genetics/Amgen
    University of Iceland)

  • Stefania Benonisdottir

    (deCODE genetics/Amgen)

  • Gudmar Thorleifsson

    (deCODE genetics/Amgen)

  • Patrick Sulem

    (deCODE genetics/Amgen)

  • Asmundur Oddsson

    (deCODE genetics/Amgen)

  • Unnur Styrkarsdottir

    (deCODE genetics/Amgen)

  • Snaedis Kristmundsdottir

    (deCODE genetics/Amgen)

  • Gudny A. Arnadottir

    (deCODE genetics/Amgen)

  • Gudmundur Thorgeirsson

    (deCODE genetics/Amgen
    University of Iceland
    Landspitali, The National University Hospital of Iceland)

  • Ingileif Jonsdottir

    (deCODE genetics/Amgen
    University of Iceland
    Landspitali, The National University Hospital of Iceland)

  • Gunnar M. Zoega

    (Landspitali, The National University Hospital of Iceland)

  • Unnur Thorsteinsdottir

    (deCODE genetics/Amgen
    University of Iceland)

  • Daniel F. Gudbjartsson

    (deCODE genetics/Amgen
    University of Iceland)

  • Fridbert Jonasson

    (University of Iceland
    Landspitali, The National University Hospital of Iceland)

  • Hilma Holm

    (deCODE genetics/Amgen)

  • Kari Stefansson

    (deCODE genetics/Amgen
    University of Iceland)

Abstract

The corneal endothelium is vital for transparency and proper hydration of the cornea. Here, we conduct a genome-wide association study of corneal endothelial cell density (cells/mm2), coefficient of cell size variation (CV), percentage of hexagonal cells (HEX) and central corneal thickness (CCT) in 6,125 Icelanders and find associations at 10 loci, including 7 novel. We assess the effects of these variants on various ocular biomechanics such as corneal hysteresis (CH), as well as eye diseases such as glaucoma and corneal dystrophies. Most notably, an intergenic variant close to ANAPC1 (rs78658973[A], frequency = 28.3%) strongly associates with decreased cell density and accounts for 24% of the population variance in cell density (β = −0.77 SD, P = 1.8 × 10−314) and associates with increased CH (β = 0.19 SD, P = 2.6 × 10−19) without affecting risk of corneal diseases and glaucoma. Our findings indicate that despite correlations between cell density and eye diseases, low cell density does not increase the risk of disease.

Suggested Citation

  • Erna V. Ivarsdottir & Stefania Benonisdottir & Gudmar Thorleifsson & Patrick Sulem & Asmundur Oddsson & Unnur Styrkarsdottir & Snaedis Kristmundsdottir & Gudny A. Arnadottir & Gudmundur Thorgeirsson &, 2019. "Sequence variation at ANAPC1 accounts for 24% of the variability in corneal endothelial cell density," Nature Communications, Nature, vol. 10(1), pages 1-10, December.
    • Handle: RePEc:nat:natcom:v:10:y:2019:i:1:d:10.1038_s41467-019-09304-9
    DOI: 10.1038/s41467-019-09304-9
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    Cited by:

    1. Yu Huang & Denis Plotnikov & Huan Wang & Danli Shi & Cong Li & Xueli Zhang & Xiayin Zhang & Shulin Tang & Xianwen Shang & Yijun Hu & Honghua Yu & Hongyang Zhang & Jeremy A. Guggenheim & Mingguang He, 2024. "GWAS-by-subtraction reveals an IOP-independent component of primary open angle glaucoma," Nature Communications, Nature, vol. 15(1), pages 1-15, December.
    2. Jonsdottir, Gudrun A. & Einarsson, Gudmundur & Thorleifsson, Gudmar & Magnusson, Sigurdur H. & Gunnarsson, Arni F. & Frigge, Michael L. & Gisladottir, Rosa S. & Unnsteinsdottir, Unnur & Gunnarsson, Bj, 2021. "Genetic propensities for verbal and spatial ability have opposite effects on body mass index and risk of schizophrenia," Intelligence, Elsevier, vol. 88(C).
    3. Andrew R. Hamel & Wenjun Yan & John M. Rouhana & Aboozar Monovarfeshani & Xinyi Jiang & Puja A. Mehta & Jayshree Advani & Yuyang Luo & Qingnan Liang & Skanda Rajasundaram & Arushi Shrivastava & Kather, 2024. "Integrating genetic regulation and single-cell expression with GWAS prioritizes causal genes and cell types for glaucoma," Nature Communications, Nature, vol. 15(1), pages 1-25, December.

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