Rare variant analyses across multiethnic cohorts identify novel genes for refractive error

Anthony M. Musolf, Annechien E.G. Haarman, Robert N. Luben, Jue Sheng Ong, Karina Patasova, Rolando Hernandez Trapero, Joseph Marsh, Ishika Jain, Riya Jain, Paul Zhiping Wang, Deyana D. Lewis, Milly S. Tedja, Hengtong Li, Cameron S. Cowan, Consortium for Refractive Error and Myopia (CREAM), Ginevra Biino, Alison P. Klein, Priya Duggal, David A. Mackey, Caroline HaywardToomas Haller, Andres Metspalu, Juho Wedenoja, Olavi Pärssinen, Cheng Ching-Yu, Seang Mei Saw, Dwight Stambolian, Pirro G Hysi, Anthony P. Khawaja, Veronique Vitart, Christopher J. Hammond, Cornelia M. van Dujin, Virginie J. M. Verhoeven, Caroline C. W. Klaver, Joan E. Bailey-Wilson

Research output: Contribution to journalArticleScientificpeer-review

2 Citations (Scopus)


Refractive error, measured here as mean spherical equivalent (SER), is a complex eye condition caused by both genetic and environmental factors. Individuals with strong positive or negative values of SER require spectacles or other approaches for vision correction. Common genetic risk factors have been identified by genome-wide association studies (GWAS), but a great part of the refractive error heritability is still missing. Some of this heritability may be explained by rare variants (minor allele frequency [MAF] ≤ 0.01.). We performed multiple gene-based association tests of mean Spherical Equivalent with rare variants in exome array data from the Consortium for Refractive Error and Myopia (CREAM). The dataset consisted of over 27,000 total subjects from five cohorts of Indo-European and Eastern Asian ethnicity. We identified 129 unique genes associated with refractive error, many of which were replicated in multiple cohorts. Our best novel candidates included the retina expressed PDCD6IP, the circadian rhythm gene PER3, and P4HTM, which affects eye morphology. Future work will include functional studies and validation. Identification of genes contributing to refractive error and future understanding of their function may lead to better treatment and prevention of refractive errors, which themselves are important risk factors for various blinding conditions.

Original languageEnglish
Article number6
JournalCommunications biology
Publication statusPublished - Jan 2023
Publication typeA1 Journal article-refereed

ASJC Scopus subject areas

  • Medicine (miscellaneous)
  • General Biochemistry,Genetics and Molecular Biology
  • General Agricultural and Biological Sciences


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