Macular thickness varies with age-related macular degeneration genetic risk variants in the UK Biobank cohort
Macular thickness varies with age-related macular degeneration genetic risk variants in the UK Biobank cohort
To evaluate the influence AMD risk genomic variants have on macular thickness in the normal population. UK Biobank participants with no significant ocular history were included using the UK Biobank Resource (project 2112). Spectral-domain optical coherence tomography (SD-OCT) images were taken and segmented to define retinal layers. The influence of AMD risk single-nucleotide polymorphisms (SNP) on retinal layer thickness was analysed. AMD risk associated SNPs were strongly associated with outer-retinal layer thickness. The inner-segment outer segment (ISOS)-retinal pigment epithelium (RPE) thickness measurement, representing photoreceptor outer segments was most significantly associated with the cumulative polygenic risk score, composed of 33 AMD-associated variants, resulting in a decreased thickness (p = 1.37 × 10–67). Gene–gene interactions involving the NPLOC4-TSPAN10 SNP rs6565597 were associated with significant changes in outer retinal thickness. Thickness of outer retinal layers is highly associated with the presence of risk AMD SNPs. Specifically, the ISOS-RPE measurement. Changes to ISOS-RPE thickness are seen in clinically normal individuals with AMD risk SNPs suggesting structural changes occur at the macula prior to the onset of disease symptoms or overt clinical signs.
Kaye, Rebecca
5736c211-ec31-441c-ac72-db1191ca935c
Patasova, Karina
3363ee53-99a2-42b5-8e5f-4eeba7c5a02d
Patel, Praveen J.
91baf7b2-de1c-40aa-b3f4-7cc7007220f2
Hysi, Pirro
dd5e8a62-9503-4738-a51a-a053d4071095
Lotery, Andrew
5ecc2d2d-d0b4-468f-ad2c-df7156f8e514
UK Biobank Eye and Vision Consortium
1 December 2021
Kaye, Rebecca
5736c211-ec31-441c-ac72-db1191ca935c
Patasova, Karina
3363ee53-99a2-42b5-8e5f-4eeba7c5a02d
Patel, Praveen J.
91baf7b2-de1c-40aa-b3f4-7cc7007220f2
Hysi, Pirro
dd5e8a62-9503-4738-a51a-a053d4071095
Lotery, Andrew
5ecc2d2d-d0b4-468f-ad2c-df7156f8e514
Kaye, Rebecca, Patasova, Karina, Patel, Praveen J., Hysi, Pirro and Lotery, Andrew
,
UK Biobank Eye and Vision Consortium
(2021)
Macular thickness varies with age-related macular degeneration genetic risk variants in the UK Biobank cohort.
Scientific Reports, 11, [23255].
(doi:10.1038/s41598-021-02631-2).
Abstract
To evaluate the influence AMD risk genomic variants have on macular thickness in the normal population. UK Biobank participants with no significant ocular history were included using the UK Biobank Resource (project 2112). Spectral-domain optical coherence tomography (SD-OCT) images were taken and segmented to define retinal layers. The influence of AMD risk single-nucleotide polymorphisms (SNP) on retinal layer thickness was analysed. AMD risk associated SNPs were strongly associated with outer-retinal layer thickness. The inner-segment outer segment (ISOS)-retinal pigment epithelium (RPE) thickness measurement, representing photoreceptor outer segments was most significantly associated with the cumulative polygenic risk score, composed of 33 AMD-associated variants, resulting in a decreased thickness (p = 1.37 × 10–67). Gene–gene interactions involving the NPLOC4-TSPAN10 SNP rs6565597 were associated with significant changes in outer retinal thickness. Thickness of outer retinal layers is highly associated with the presence of risk AMD SNPs. Specifically, the ISOS-RPE measurement. Changes to ISOS-RPE thickness are seen in clinically normal individuals with AMD risk SNPs suggesting structural changes occur at the macula prior to the onset of disease symptoms or overt clinical signs.
Text
s41598-021-02631-2
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More information
Accepted/In Press date: 16 November 2021
e-pub ahead of print date: 1 December 2021
Published date: 1 December 2021
Additional Information:
Acknowledgements
The research was supported by the NIHR Biomedical Research Centre at Moorfields Eye Hospital NHS Foundation Trust and UCL Institute of Ophthalmology. The views expressed are those of the author(s) and not necessarily those of the NHS, the NIHR or the Department of Health. The UK Biobank Eye and Vision Consortium is supported by Grants from Moorfields Eye Charity, The NIHR Biomedical Research Centre at Moorfields Eye Hospital NHS Foundation Trust (BRC2_009) and UCL Institute of Ophthalmology and the Alcon Research Institute. Members of the consortium who did not contribute directly to this manuscript are listed in the Supplementary Information file. This work was supported by the Wellcome Trust [210572/Z/18/Z]. K.Patasova is a grateful recipient of a Fight for Sight studentship.
Funding
The funding was provided by a Wellcome Trust grant [210572/Z/18/Z] supporting R.K. and a Fight for Sight studentship supporting K.P.
Identifiers
Local EPrints ID: 452337
URI: http://eprints.soton.ac.uk/id/eprint/452337
ISSN: 2045-2322
PURE UUID: ba1161c1-35b5-47b8-adba-8307f559fefb
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Date deposited: 08 Dec 2021 18:43
Last modified: 17 Mar 2024 04:01
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Contributors
Author:
Rebecca Kaye
Author:
Karina Patasova
Author:
Praveen J. Patel
Author:
Pirro Hysi
Corporate Author: UK Biobank Eye and Vision Consortium
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