Background Pathological myopia is one of the leading causes of blindness globally. Lower birth weight (BW) within the normal range has been reported to increase the risk of myopia, although findings conflict. We sought to estimate the causal effect of BW on refractive error using Mendelian randomisation (MR), under the assumption of a linear relationship.
Methods Genetic variants associated with BW were identified from meta-analysis of a genome-wide association study (GWAS) for self-reported BW in 162 039 UK Biobank participants and a published Early Growth Genetics (EGG) consortium GWAS (n=26 836). We performed a one-sample MR analysis in 39 658 unrelated, adult UK Biobank participants (independent of the GWAS sample) using an allele score for BW as instrumental variable. A two-sample MR sensitivity analysis and conventional ordinary least squares (OLS) regression analyses were also undertaken.
Results In OLS analysis, BW showed a small, positive association with refractive error: +0.04 D per SD increase in BW (95% CI 0.02 to 0.07; p=0.002). The one-sample MR-estimated causal effect of BW on refractive error was higher, at +0.28 D per SD increase in BW (95% CI 0.05 to 0.52, p=0.02). A two-sample MR analysis provided similar causal effect estimates, with minimal evidence of directional pleiotropy.
Conclusions Our study suggests lower BW within the normal range is causally associated with a more myopic refractive error. However, the impact of the causal effect was modest (range 1.00 D covering approximately 95% of the population).
- refractive error
- birth weight
- Mendelian randomisation
- UK Biobank
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Contributors DP, CW and JG contributed to the conception and design of the study. DP carried out the analysis. All authors were involved in drafting, critically reviewing and approval of the manuscript.
Funding This research has been conducted using the UK Biobank Resource (applications #17351 and #17615). Data analysis was carried out using the RAVEN computing cluster, maintained by the ARCCA group at Cardiff University and the BLUE CRYSTAL3 computing cluster maintained by the HPC group at the University of Bristol. This research was specifically funded by NIHR Senior Research Fellowship award SRF-2015-08-005 and the Global Education Program of the Russian Federation government. UK Biobank was established by the Wellcome Trust; the UK Medical Research Council; the Department for Health (London, UK); Scottish Government (Edinburgh, UK); the Northwest Regional Development Agency (Warrington, UK). It also received funding from the Welsh Assembly Government (Cardiff, UK); the British Heart Foundation; Diabetes UK. Collection of eye and vision data were supported by The Department for Health through an award made by the NIHR to the Biomedical Research Centre at Moorfields Eye Hospital NHS Foundation Trust, and UCL Institute of Ophthalmology, London, UK (grant no. BRC2_009). Additional support was provided by The Special Trustees of Moorfields Eye Hospital, London, UK (grant no. ST 12 09).
Competing interests None declared.
Patient consent for publication All participants provided written informed consent.
Ethics approval Ethical approval was obtained from the National Health Research Ethics Service (Ref 11/NW/0382).
Provenance and peer review Not commissioned; externally peer reviewed.
Data availability statement Data may be obtained from a third party and are not publicly available.