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

作者：Weixiong He, Peter J. van der Most, Jue‐Sheng Ong, Liang‐Dar Hwang, Yeda Wu, Morten Schjerven Magnø, Jelle Vehof, Kristi Krebs, L. Mauring, Katrin Õunap, Erik Abner, Nicholas G. Martin, Denis Plotnikov, Chen Jiang, Ronald B. Melles, Puya Gharahkhani, Harold Snieder, Teele Palumaa, Kuldar Kaljurand, Jeremy A. Guggenheim, David A. Mackey, Elizabeth C. Engle, Hélène Choquet, Lifelines Cohort Study, Raúl Aguirre‐Gamboa, Patrick Deelen, Lude Franke, Jan Albert Kuivenhoven, Esteban A. Lopera-Maya, Ilja M. Nolte, Serena Sanna, Morris A. Swertz, Peter M. Visscher, Judith M. Vonk, Cisca Wijmenga, Naomi R. Wray, Stuart MacGregor · 发表于：Nature Communications · 年份：2025 · DOI：10.1038/s41467-025-62456-9 · 被引用次数：7 · 研究领域：Genetic Associations and Epidemiology、Liver Disease Diagnosis and Treatment、Birth, Development, and Health

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. This large meta-analysis of 11 GWAS identified 7 genetic loci associated with strabismus, esotropia and exotropia. Mendelian randomisation provided genetic evidence of the causal link between maternal smoking to increased strabismus risk in offspring.