机构：[1]School of Public Health and Preventive Medicine, Monash University, Melbourne, VIC, Australia.[2]Victorian Heart Institute, Monash University, Clayton, VIC, Australia.[3]Centre for Eye Research Australia, The University of Melbourne, Melbourne, VIC, Australia.[4]Centre for Healthy Brain Ageing (CHeBA), School of Psychiatry, University of New South Wales, Kensington, NSW, Australia.[5]Department of Geriatric Medicine, Prince of Wales Hospital, Randwick, NSW, Australia.[6]School of Medicine and Psychology, The Australian National University, Canberra, Australia.[7]Royal Victorian Eye and Ear Hospital, Melbourne, VIC, Australia.[8]Turner Institute for Brain and Mental Health, School of Psychological Sciences, Monash University, Clayton, VIC, Australia.[9]Industrial Transformation Training Centre for Optimal Ageing, School of Psychological Sciences, Monash University, Clayton, VIC, Australia.[10]Institute of Molecular Bioscience, University of Queensland, Brisbane, QLD, Australia.[11]Saw Swee Hock School of Public Health, National University of Singapore and National University Health System, Singapore, Singapore.[12]School of Clinical Medicine, Beijing Tsinghua Changgang Hospital, Tsinghua Medicine, Tsinghua University, Beijing, China.[13]Beijing Visual Science and Translational Eye Research Institute (BERI), Beijing Key Laboratory of Intelligent Diagnostic Technology and Devices for Major Blinding Eye Diseases, Tsinghua University, Beijing, China.[14]Singapore Eye Research Institute, Singapore National Eye Center, Singapore, Singapore.[15]QIMR Berghofer Medical Research Institute, Brisbane, QLD, Australia.[16]School of Medicine, University of Queensland, Brisbane, QLD, Australia.
Retinal vessel calibers are genetically heritable, quantitatively measured, and noninvasive ocular biomarkers of microvascular health. Despite their heritability identified from genome-wide association studies (GWASs), polygenic scores (PGSs) for these traits have not been developed. We aimed to calculate PGSs and associate them with retinal vessel caliber phenotypes in older adults.Our study included 3717 individuals of European ancestry aged ≥70 years with retinal imaging and genome-wide genotype data. Retinal vessel calibers were measured from fundus photographs and summarized as central retinal arteriolar equivalent (CRAE) and central retinal venular equivalent (CRVE). PGSs for each trait were constructed using the SBayesRC method, incorporating prior GWAS summary statistics. Associations between PGSs and measured CRAE and CRVE were examined using linear regression, adjusting for demographic and clinical covariates.Both PGSs were associated with their corresponding retinal vessel calibers. In fully adjusted models, each standard deviation increase in the CRAE and CRVE PGSs was associated with a 1.53 and 3.89 µm increase in vessel diameter, respectively (both P < 0.0001). Fully adjusted models explained 6.0% of CRAE and 7.1% of CRVE variance. A dose-response pattern was observed across increasing PGS quartiles for CRAE and CRVE. Participants in the highest PGS quartile, versus the lowest, had 4.23 µm wider arterioles for CRAE, and 9.50 µm wider venules for CRVE (both P < 0.0001).PGSs for CRAE and CRVE are associated with measured retinal microvascular phenotypes. These findings illustrate the genetic contribution to retinal vessel calibers and provide insights into mechanisms of microvascular and macrovascular health.
基金：
the National Institute on Aging and the National
Cancer Institute, National Institutes of Health, Bethesda, Maryland (grant no.: U01AG029824); the National Health and Medical
Research Council of Australia (grant nos.: 334047 and 1127060);
Monash University (Australia); and the Victorian Cancer Agency
(Australia). The ASPREE-AMD substudy was supported by the
National Health and Medical Research Council of Australia
(grant no.: 1051625); the National Eye Institute, National Institutes of Health (grant no.: R01EY026890); Monash University; and the Centre for Eye Research Australia. The ENVISion substudy was supported by the National Health and Medical Research Council of Australia (grant no.: 471460). The
SNORE-ASA substudy was funded by the National Health and
Medical Research Council of Australia (grant no.: 1028368).
C.Y. is supported by a Vanguard Grant (grant no.: 108071-
2024_VG) from the National Heart Foundation of Australia. P.L.
is supported by a National Heart Foundation Future Leader
Fellowship (grant no.: 107171) and National Health and Medical Research Council of Australia Investigator Grant (grant no.:
2026325). J.J.M. is supported by a National Health and Medical Research Council of Australia Leadership Fellowship (grant
no.: IG1173690). R.H.G. is supported by the National Health and
Medical Research Council of Australia (grant no.: 1194667). S.M.
is supported by the National Health and Medical Research Council of Australia (grant nos.: 2034568, 1150144 and 1116360).
R.W. is supported by the National Institute on Aging (grant
no.: U19AG062682) and the National Eye Institute (grant no.:
1R01EY026890-01), National Institutes of Health.
语种：
外文
PubmedID：
中科院(CAS)分区：
出版当年[2025]版：
大类|2 区医学
小类|2 区眼科学
最新[2025]版：
大类|2 区医学
小类|2 区眼科学
第一作者：
第一作者机构：[1]School of Public Health and Preventive Medicine, Monash University, Melbourne, VIC, Australia.[2]Victorian Heart Institute, Monash University, Clayton, VIC, Australia.
通讯作者：
通讯机构：[1]School of Public Health and Preventive Medicine, Monash University, Melbourne, VIC, Australia.[2]Victorian Heart Institute, Monash University, Clayton, VIC, Australia.
推荐引用方式(GB/T 7714)：
Yu Chenglong,Rupasinghe Nuwanthi,Robman Liubov,et al.Development and Validation of Polygenic Scores for Retinal Vessel Calibers[J].Investigative Ophthalmology & Visual Science.2025,66(13):9.doi:10.1167/iovs.66.13.9.
APA：
Yu Chenglong,Rupasinghe Nuwanthi,Robman Liubov,Hodgson Lauren A B,Pham Thao...&Lacaze Paul.(2025).Development and Validation of Polygenic Scores for Retinal Vessel Calibers.Investigative Ophthalmology & Visual Science,66,(13)
MLA：
Yu Chenglong,et al."Development and Validation of Polygenic Scores for Retinal Vessel Calibers".Investigative Ophthalmology & Visual Science 66..13(2025):9
