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Uncovering genetic loci and biological pathways associated with age-related cataracts through GWAS meta-analysis

Author

Listed:
  • Santiago Diaz-Torres

    (QIMR Berghofer Medical Research Institute
    The University of Queensland)

  • Samantha Sze-Yee Lee

    (The University of Western Australia)

  • Luis M. García-Marín

    (QIMR Berghofer Medical Research Institute
    The University of Queensland)

  • Adrian I. Campos

    (QIMR Berghofer Medical Research Institute
    The University of Queensland
    Regeneron Genetics Center)

  • Garreth Lingham

    (The University of Western Australia)

  • Jue-Sheng Ong

    (QIMR Berghofer Medical Research Institute)

  • David A. Mackey

    (The University of Western Australia)

  • Kathryn P. Burdon

    (University of Tasmania)

  • Michael Hunter

    (The University of Western Australia)

  • Xianjun Dong

    (Brigham and Women’s Hospital and Harvard Medical School
    Brigham and Women’s Hospital and Harvard Medical School)

  • Stuart MacGregor

    (QIMR Berghofer Medical Research Institute
    The University of Queensland)

  • Puya Gharahkhani

    (QIMR Berghofer Medical Research Institute
    The University of Queensland
    Queensland University of Technology (QUT))

  • Miguel E. Rentería

    (QIMR Berghofer Medical Research Institute
    The University of Queensland)

Abstract

Age-related cataracts is a highly prevalent eye disorder that results in the clouding of the crystalline lens and is one of the leading causes of visual impairment and blindness. The disease is influenced by multiple factors including genetics, prolonged exposure to ultraviolet radiation, and a history of diabetes. However, the extent to which each of these factors contributes to the development of cataracts remains unclear. Our study identified 101 independent genome-wide significant loci, 57 of which are novel. We identified multiple genes and biological pathways associated with the cataracts, including four drug-gene interactions. Our results suggest a causal association between type 1 diabetes and cataracts. Also, we highlighted a surrogate measure of UV light exposure as a marker of cataract risk in adults.

Suggested Citation

  • Santiago Diaz-Torres & Samantha Sze-Yee Lee & Luis M. García-Marín & Adrian I. Campos & Garreth Lingham & Jue-Sheng Ong & David A. Mackey & Kathryn P. Burdon & Michael Hunter & Xianjun Dong & Stuart M, 2024. "Uncovering genetic loci and biological pathways associated with age-related cataracts through GWAS meta-analysis," Nature Communications, Nature, vol. 15(1), pages 1-10, December.
    • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-53212-6
    DOI: 10.1038/s41467-024-53212-6
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    References listed on IDEAS

    as
    1. Christiaan A de Leeuw & Joris M Mooij & Tom Heskes & Danielle Posthuma, 2015. "MAGMA: Generalized Gene-Set Analysis of GWAS Data," PLOS Computational Biology, Public Library of Science, vol. 11(4), pages 1-19, April.
    2. Mitja I. Kurki & Juha Karjalainen & Priit Palta & Timo P. Sipilä & Kati Kristiansson & Kati M. Donner & Mary P. Reeve & Hannele Laivuori & Mervi Aavikko & Mari A. Kaunisto & Anu Loukola & Elisa Lahtel, 2023. "Author Correction: FinnGen provides genetic insights from a well-phenotyped isolated population," Nature, Nature, vol. 615(7952), pages 19-19, March.
    3. Zhihong Zhu & Zhili Zheng & Futao Zhang & Yang Wu & Maciej Trzaskowski & Robert Maier & Matthew R. Robinson & John J. McGrath & Peter M. Visscher & Naomi R. Wray & Jian Yang, 2018. "Causal associations between risk factors and common diseases inferred from GWAS summary data," Nature Communications, Nature, vol. 9(1), pages 1-12, December.
    4. Heli Julkunen & Anna Cichońska & Mika Tiainen & Harri Koskela & Kristian Nybo & Valtteri Mäkelä & Jussi Nokso-Koivisto & Kati Kristiansson & Markus Perola & Veikko Salomaa & Pekka Jousilahti & Annamar, 2023. "Atlas of plasma NMR biomarkers for health and disease in 118,461 individuals from the UK Biobank," Nature Communications, Nature, vol. 14(1), pages 1-15, December.
    5. Seula Shin & Hao Zhou & Chenxi He & Yanjun Wei & Yunfei Wang & Takashi Shingu & Ailiang Zeng & Shaobo Wang & Xin Zhou & Hongtao Li & Qiang Zhang & Qinling Mo & Jiafu Long & Fei Lan & Yiwen Chen & Jian, 2021. "Qki activates Srebp2-mediated cholesterol biosynthesis for maintenance of eye lens transparency," Nature Communications, Nature, vol. 12(1), pages 1-18, December.
    6. Joshua Chiou & Ryan J. Geusz & Mei-Lin Okino & Jee Yun Han & Michael Miller & Rebecca Melton & Elisha Beebe & Paola Benaglio & Serina Huang & Katha Korgaonkar & Sandra Heller & Alexander Kleger & Seba, 2021. "Interpreting type 1 diabetes risk with genetics and single-cell epigenomics," Nature, Nature, vol. 594(7863), pages 398-402, June.
    7. repec:plo:pone00:0218857 is not listed on IDEAS
    8. Mitja I. Kurki & Juha Karjalainen & Priit Palta & Timo P. Sipilä & Kati Kristiansson & Kati M. Donner & Mary P. Reeve & Hannele Laivuori & Mervi Aavikko & Mari A. Kaunisto & Anu Loukola & Elisa Lahtel, 2023. "FinnGen provides genetic insights from a well-phenotyped isolated population," Nature, Nature, vol. 613(7944), pages 508-518, January.
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