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

He, Weixiong, van der Most, Peter J., Ong, Jue-Sheng, Hwang, Liang-Dar, Wu, Yeda, Magnø, Morten S., Vehof, Jelle, Krebs, Kristi, Mauring, Laura, Õunap, Katrin, Abner, Erik, Martin, Nicholas G., Plotnikov, Denis, Jiang, Chen, Melles, Ronald B., Gharahkhani, Puya, Snieder, Harold, Palumaa, Teele, Kaljurand, Kuldar, Guggenheim, Jeremy A. ORCID: https://orcid.org/0000-0001-5164-340X, Mackey, David A., Engle, Elizabeth C., Choquet, Hélène, Aguirre-Gamboa, Raul, Deelen, Patrick, Franke, Lude, Kuivenhoven, Jan A., Maya, Esteban A. Lopera, Nolte, Ilja M., Sanna, Serena, Swertz, Morris A., Visscher, Peter M., Vonk, Judith M., Wijmenga, Cisca, Wray, Naomi and MacGregor, Stuart 2025. Large-scale GWAS of strabismus identifies risk loci and provides support for a link with maternal smoking. Nature Communications 16 (1) , 7890. 10.1038/s41467-025-62456-9

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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.

Item Type:	Article
Date Type:	Published Online
Status:	Published
Schools:	Schools > Optometry and Vision Sciences
Publisher:	Nature Research
ISSN:	2041-1723
Date of First Compliant Deposit:	25 August 2025
Date of Acceptance:	19 July 2025
Last Modified:	26 Aug 2025 09:30
URI:	https://orca.cardiff.ac.uk/id/eprint/180612

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