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| PMID |
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| TITLE |
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| Large-scale GWAS of strabismus identifies risk loci and provides support for a link with maternal smoking. |
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| ABSTRACT |
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| 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. |
| © 2025. The Author(s). |
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| DATE PUBLISHED |
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| HISTORY |
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| PUBSTATUS |
PUBSTATUSDATE |
| received |
2023/08/22 |
| accepted |
2025/07/19 |
| medline |
2025/08/26 04:47 |
| pubmed |
2025/08/26 04:46 |
| entrez |
2025/08/23 23:21 |
| pmc-release |
2025/08/23 |
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| AUTHORS |
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| NAME |
COLLECTIVENAME |
LASTNAME |
FORENAME |
INITIALS |
AFFILIATION |
AFFILIATIONINFO |
| He W |
|
He |
Weixiong |
W |
|
Faculty of Medicine, University of Queensland, Brisbane, QLD, Australia. weixiong.he@uq.net.au. |
| van der Most PJ |
|
van der Most |
Peter J |
PJ |
|
Department of Epidemiology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands. |
| Ong JS |
|
Ong |
Jue-Sheng |
JS |
|
QIMR Berghofer Medical Research Institute, Brisbane, QLD, Australia. |
| Hwang LD |
|
Hwang |
Liang-Dar |
LD |
|
Institute for Molecular Bioscience, University of Queensland, Brisbane, QLD, Australia. |
| Wu Y |
|
Wu |
Yeda |
Y |
|
QIMR Berghofer Medical Research Institute, Brisbane, QLD, Australia. |
| Magnø MS |
|
Magnø |
Morten S |
MS |
|
Department of Medical Biochemistry, Oslo University Hospital, Oslo, Norway. |
| Vehof J |
|
Vehof |
Jelle |
J |
|
Department of Ophthalmology, Vestfold Hospital Trust, Tønsberg, Norway. |
| Krebs K |
|
Krebs |
Kristi |
K |
|
Estonian Genome Center, Institute of Genomics, University of Tartu, Tartu, Estonia. |
| Mauring L |
|
Mauring |
Laura |
L |
|
Eye Clinic, Tartu University Hospital, Tartu, Estonia. |
| Õunap K |
|
Õunap |
Katrin |
K |
|
Department of Genetics and Personalized Medicine, Institute of Clinical Medicine, University of Tartu, Tartu, Estonia. |
| Abner E |
|
Abner |
Erik |
E |
|
Estonian Genome Center, Institute of Genomics, University of Tartu, Tartu, Estonia. |
| Martin NG |
|
Martin |
Nicholas G |
NG |
|
QIMR Berghofer Medical Research Institute, Brisbane, QLD, Australia. |
| Plotnikov D |
|
Plotnikov |
Denis |
D |
|
Central Research Laboratory, Kazan State Medical University, Kazan, Russia. |
| Jiang C |
|
Jiang |
Chen |
C |
|
Division of Research, Kaiser Permanente Northern California, Oakland, CA, USA. |
| Melles RB |
|
Melles |
Ronald B |
RB |
|
Division of Research, Kaiser Permanente Northern California, Oakland, CA, USA. |
| Gharahkhani P |
|
Gharahkhani |
Puya |
P |
|
Faculty of Medicine, University of Queensland, Brisbane, QLD, Australia. |
| Snieder H |
|
Snieder |
Harold |
H |
|
Department of Epidemiology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands. |
| Palumaa T |
|
Palumaa |
Teele |
T |
|
Eye Clinic, East Tallinn Central Hospital, Tallinn, Estonia. |
| Kaljurand K |
|
Kaljurand |
Kuldar |
K |
|
Department of Eye Clinic, Institute of Clinical Medicine, University of Tartu, Tartu, Estonia. |
| Guggenheim JA |
|
Guggenheim |
Jeremy A |
JA |
|
School of Optometry & Vision Sciences, Cardiff University, Cardiff, UK. |
| Mackey DA |
|
Mackey |
David A |
DA |
|
Lions Eye Institute, Centre for Ophthalmology and Visual Science, University of Western Australia, Perth, WA, Australia. |
| Engle EC |
|
Engle |
Elizabeth C |
EC |
|
Howard Hughes Medical Institute, Chevy Chase, MD, USA. |
| Choquet H |
|
Choquet |
Hélène |
H |
|
Division of Research, Kaiser Permanente Northern California, Oakland, CA, USA. |
|
Lifelines Cohort Study |
|
|
|
|
|
| MacGregor S |
|
MacGregor |
Stuart |
S |
|
Faculty of Medicine, University of Queensland, Brisbane, QLD, Australia. |
|
| INVESTIGATORS |
|
| LASTNAME |
FORENAME |
INITIALS |
AFFILIATION |
| Aguirre-Gamboa |
Raul |
R |
|
| Deelen |
Patrick |
P |
|
| Franke |
Lude |
L |
|
| Kuivenhoven |
Jan A |
JA |
|
| Maya |
Esteban A Lopera |
EAL |
|
| Nolte |
Ilja M |
IM |
|
| Sanna |
Serena |
S |
|
| Swertz |
Morris A |
MA |
|
| Visscher |
Peter M |
PM |
|
| Vonk |
Judith M |
JM |
|
| Wijmenga |
Cisca |
C |
|
| Wray |
Naomi |
N |
|
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| JOURNAL |
|
| VOLUME: 16 |
| ISSUE: 1 |
| TITLE: Nature communications |
| ISOABBREVIATION: Nat Commun |
| YEAR: 2025 |
| MONTH: Aug |
| DAY: 23 |
| MEDLINEDATE: |
| SEASON: |
| CITEDMEDIUM: Internet |
| ISSN: 2041-1723 |
| ISSNTYPE: Electronic |
|
| MEDLINE JOURNAL |
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| MEDLINETA: Nat Commun |
| COUNTRY: England |
| ISSNLINKING: 2041-1723 |
| NLMUNIQUEID: 101528555 |
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| PUBLICATION TYPE |
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| PUBLICATIONTYPE TEXT |
| Journal Article |
| Meta-Analysis |
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| COMMENTS AND CORRECTIONS |
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| GRANTS |
|
| GRANTID |
AGENCY |
COUNTRY |
| R01 EY027004 |
NEI NIH HHS |
United States |
| R01 EY033010 |
NEI NIH HHS |
United States |
| RC2 AG036607 |
NIA NIH HHS |
United States |
|
| GENERAL NOTE |
|
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| KEYWORDS |
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| MESH HEADINGS |
|
| DESCRIPTORNAME |
QUALIFIERNAME |
| Humans |
|
| Genome-Wide Association Study |
|
| Female |
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| Strabismus |
etiology |
| Smoking |
adverse effects |
| Genetic Predisposition to Disease |
adverse effects |
| Risk Factors |
adverse effects |
| Polymorphism, Single Nucleotide |
adverse effects |
| Mendelian Randomization Analysis |
adverse effects |
| Male |
adverse effects |
| Pregnancy |
adverse effects |
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| SUPPLEMENTARY MESH |
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| GENE SYMBOLS |
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| CHEMICALS |
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| OTHER ID's |
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