Nguyen, Thu Nga, Terry, Louise  ORCID: https://orcid.org/0000-0002-6200-8230 and Guggenheim, Jeremy A. ORCID: https://orcid.org/0000-0001-5164-340X
2025.
Mendelian randomization studies of myopia: choosing the right summary statistics.
Investigative Ophthalmology & Visual Science
66
(13)
, 57.
10.1167/iovs.66.13.57
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Abstract
Purpose: To examine whether the choice of genome-wide association study (GWAS) summary statistics can yield invalid or misleading conclusions in Mendelian randomization (MR) studies of myopia. Methods: The relationships between (1) years of full-time education and myopia, and (2) myopia and primary open-angle glaucoma (POAG), were used as exemplar test cases. MR analyses were performed with nine different sets of summary statistics for myopia: seven from sources widely used in published MR studies, plus two newly derived sets (a GWAS for myopia in either 66,773 unrelated participants or 93,036 participants that included relatives). Results: Using the two newly derived sets of summary statistics from GWAS for myopia in unrelated and related samples, MR analyses demonstrated a positive causal relationship between education and myopia: odds ratio (OR) for myopia = 1.18, 95% confidence interval (CI) = 1.10 to 1.26 and OR = 1.16, 95% CI = 1.09 to 1.23 per additional year of education, respectively, and a positive relationship between myopia and POAG: OR = 1.11, 95% CI = 1.03 to 1.19 and OR = 1.12, 95% CI = 1.03 to 1.21, respectively. MR analyses performed using existing published GWAS summary statistics yielded inconsistent results, including MR estimates that suggested education protected against myopia and that myopia reduced the risk of POAG. Re-analysis of a selection of published MR studies of myopia confirmed that most published results were invalid. Conclusions: Care is required when designing MR analyses. Many published MR studies of myopia have reported misleading results.
| Item Type: | Article |
|---|---|
| Date Type: | Publication |
| Status: | Published |
| Schools: | Schools > Optometry and Vision Sciences |
| Publisher: | Association for Research in Vision and Ophthalmology |
| ISSN: | 1552-5783 |
| Funders: | UKRI EP/Y032292/1 |
| Date of First Compliant Deposit: | 31 October 2025 |
| Date of Acceptance: | 14 October 2025 |
| Last Modified: | 04 Nov 2025 15:30 |
| URI: | https://orca.cardiff.ac.uk/id/eprint/182033 |
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