Large-scale GWAS of strabismus identifies risk loci and provides support for a link with maternal smoking
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...
Saved in:
| Main Authors: | , , , , , , , , , , , , , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Nature Portfolio
2025-08-01
|
| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-025-62456-9 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1849226109313351680 |
|---|---|
| author | Weixiong He Peter J. van der Most Jue-Sheng Ong Liang-Dar Hwang Yeda Wu Morten S. Magnø Jelle Vehof Kristi Krebs Laura 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 Stuart MacGregor |
| author_facet | Weixiong He Peter J. van der Most Jue-Sheng Ong Liang-Dar Hwang Yeda Wu Morten S. Magnø Jelle Vehof Kristi Krebs Laura 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 Stuart MacGregor |
| author_sort | Weixiong He |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-022eb5fe224c4ddfa1f9cb4a15ccd649 |
| institution | Kabale University |
| issn | 2041-1723 |
| language | English |
| publishDate | 2025-08-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Nature Communications |
| spelling | doaj-art-022eb5fe224c4ddfa1f9cb4a15ccd6492025-08-24T11:37:43ZengNature PortfolioNature Communications2041-17232025-08-0116111410.1038/s41467-025-62456-9Large-scale GWAS of strabismus identifies risk loci and provides support for a link with maternal smokingWeixiong He0Peter J. van der Most1Jue-Sheng Ong2Liang-Dar Hwang3Yeda Wu4Morten S. Magnø5Jelle Vehof6Kristi Krebs7Laura Mauring8Katrin Õunap9Erik Abner10Nicholas G. Martin11Denis Plotnikov12Chen Jiang13Ronald B. Melles14Puya Gharahkhani15Harold Snieder16Teele Palumaa17Kuldar Kaljurand18Jeremy A. Guggenheim19David A. Mackey20Elizabeth C. Engle21Hélène Choquet22Lifelines Cohort StudyStuart MacGregor23QIMR Berghofer Medical Research InstituteDepartment of Epidemiology, University Medical Center Groningen, University of GroningenQIMR Berghofer Medical Research InstituteInstitute for Molecular Bioscience, University of QueenslandQIMR Berghofer Medical Research InstituteDepartment of Ophthalmology, University Medical Center Groningen, University of GroningenDepartment of Twin Research and Genetic Epidemiology, King’s College LondonEstonian Genome Center, Institute of Genomics, University of TartuGenetics and Personalized Medicine Clinic, Tartu University HospitalGenetics and Personalized Medicine Clinic, Tartu University HospitalEstonian Genome Center, Institute of Genomics, University of TartuQIMR Berghofer Medical Research InstituteCentral Research Laboratory, Kazan State Medical UniversityDivision of Research, Kaiser Permanente Northern CaliforniaDivision of Research, Kaiser Permanente Northern CaliforniaQIMR Berghofer Medical Research InstituteDepartment of Epidemiology, University Medical Center Groningen, University of GroningenEstonian Genome Center, Institute of Genomics, University of TartuEye Clinic, Tartu University HospitalSchool of Optometry & Vision Sciences, Cardiff UniversityLions Eye Institute, Centre for Ophthalmology and Visual Science, University of Western AustraliaDepartment of Ophthalmology, Boston Children’s Hospital and Harvard Medical SchoolDivision of Research, Kaiser Permanente Northern CaliforniaQIMR Berghofer Medical Research InstituteAbstract 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.https://doi.org/10.1038/s41467-025-62456-9 |
| spellingShingle | Weixiong He Peter J. van der Most Jue-Sheng Ong Liang-Dar Hwang Yeda Wu Morten S. Magnø Jelle Vehof Kristi Krebs Laura 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 Stuart MacGregor Large-scale GWAS of strabismus identifies risk loci and provides support for a link with maternal smoking Nature Communications |
| title | Large-scale GWAS of strabismus identifies risk loci and provides support for a link with maternal smoking |
| title_full | Large-scale GWAS of strabismus identifies risk loci and provides support for a link with maternal smoking |
| title_fullStr | Large-scale GWAS of strabismus identifies risk loci and provides support for a link with maternal smoking |
| title_full_unstemmed | Large-scale GWAS of strabismus identifies risk loci and provides support for a link with maternal smoking |
| title_short | Large-scale GWAS of strabismus identifies risk loci and provides support for a link with maternal smoking |
| title_sort | large scale gwas of strabismus identifies risk loci and provides support for a link with maternal smoking |
| url | https://doi.org/10.1038/s41467-025-62456-9 |
| work_keys_str_mv | AT weixionghe largescalegwasofstrabismusidentifiesrisklociandprovidessupportforalinkwithmaternalsmoking AT peterjvandermost largescalegwasofstrabismusidentifiesrisklociandprovidessupportforalinkwithmaternalsmoking AT jueshengong largescalegwasofstrabismusidentifiesrisklociandprovidessupportforalinkwithmaternalsmoking AT liangdarhwang largescalegwasofstrabismusidentifiesrisklociandprovidessupportforalinkwithmaternalsmoking AT yedawu largescalegwasofstrabismusidentifiesrisklociandprovidessupportforalinkwithmaternalsmoking AT mortensmagnø largescalegwasofstrabismusidentifiesrisklociandprovidessupportforalinkwithmaternalsmoking AT jellevehof largescalegwasofstrabismusidentifiesrisklociandprovidessupportforalinkwithmaternalsmoking AT kristikrebs largescalegwasofstrabismusidentifiesrisklociandprovidessupportforalinkwithmaternalsmoking AT lauramauring largescalegwasofstrabismusidentifiesrisklociandprovidessupportforalinkwithmaternalsmoking AT katrinounap largescalegwasofstrabismusidentifiesrisklociandprovidessupportforalinkwithmaternalsmoking AT erikabner largescalegwasofstrabismusidentifiesrisklociandprovidessupportforalinkwithmaternalsmoking AT nicholasgmartin largescalegwasofstrabismusidentifiesrisklociandprovidessupportforalinkwithmaternalsmoking AT denisplotnikov largescalegwasofstrabismusidentifiesrisklociandprovidessupportforalinkwithmaternalsmoking AT chenjiang largescalegwasofstrabismusidentifiesrisklociandprovidessupportforalinkwithmaternalsmoking AT ronaldbmelles largescalegwasofstrabismusidentifiesrisklociandprovidessupportforalinkwithmaternalsmoking AT puyagharahkhani largescalegwasofstrabismusidentifiesrisklociandprovidessupportforalinkwithmaternalsmoking AT haroldsnieder largescalegwasofstrabismusidentifiesrisklociandprovidessupportforalinkwithmaternalsmoking AT teelepalumaa largescalegwasofstrabismusidentifiesrisklociandprovidessupportforalinkwithmaternalsmoking AT kuldarkaljurand largescalegwasofstrabismusidentifiesrisklociandprovidessupportforalinkwithmaternalsmoking AT jeremyaguggenheim largescalegwasofstrabismusidentifiesrisklociandprovidessupportforalinkwithmaternalsmoking AT davidamackey largescalegwasofstrabismusidentifiesrisklociandprovidessupportforalinkwithmaternalsmoking AT elizabethcengle largescalegwasofstrabismusidentifiesrisklociandprovidessupportforalinkwithmaternalsmoking AT helenechoquet largescalegwasofstrabismusidentifiesrisklociandprovidessupportforalinkwithmaternalsmoking AT lifelinescohortstudy largescalegwasofstrabismusidentifiesrisklociandprovidessupportforalinkwithmaternalsmoking AT stuartmacgregor largescalegwasofstrabismusidentifiesrisklociandprovidessupportforalinkwithmaternalsmoking |