Genetic insights into foveal morphology and its associations with pigmentation and age-related macular degeneration
Abstract The fovea is the small depression at the neurosensory retina that underlies high-resolution central vision. It is vulnerable to disease and disruption of its architecture can lead to visual disability. Foveal morphology varies substantially across individuals but the molecular causes and functional consequences of this variation remain incompletely understood. Here, we analyse six foveal morphological parameters derived from optical coherence tomography (OCT) images of 39,521 UK Biobank participants. We find marked variation in foveal morphology and identify significant associations with sex and genetic ancestry. Genome-wide association studies identify 162 lead loci across the six foveal morphological parameters, implicating genes involved in pigmentation (including TYR , TSPAN10 and GPR143 ) and developmental patterning (including FGFR2 , CYP26C1 and CYP1A1 ). Heritability estimates range from 29 to 43%. Foveal pit volume is associated with future risk of age-related macular degeneration (AMD) (hazard ratio 1.09, p = 0.026), a finding supported by Mendelian randomisation. Given the strong correlations among foveal traits, the specificify of this association to pit volume remains unclear. These results establish foveal morphology as a highly heritable trait that is biologically linked to AMD.
Authors
- Tomas W. Fitzgerald (ORCID: https://orcid.org/0000-0002-2370-8496)
- Marcus Fruttiger (ORCID: https://orcid.org/0000-0002-6962-5485)
- Konstantinos Balaskas (ORCID: https://orcid.org/0000-0002-7690-6277)
- Pirro G. Hysi (ORCID: https://orcid.org/0000-0001-5752-2510)
- Simon Harding (ORCID: https://orcid.org/0000-0003-1993-1051)
- Gerassimos Lascaratos (ORCID: https://orcid.org/0000-0001-5936-1431)
- Chris Hammond
- Usha Chakravarthy (ORCID: https://orcid.org/0000-0002-2606-3734)
- Parul Desai (ORCID: https://orcid.org/0000-0002-7532-972X)
- Thomas Henry Julian (ORCID: https://orcid.org/0000-0002-5488-5620)
- Denize Atan (ORCID: https://orcid.org/0000-0003-1217-4852)
- Constance L. Cepko (ORCID: https://orcid.org/0000-0002-9945-6387)
- Graeme Black (ORCID: https://orcid.org/0000-0002-3422-9175)
- Graeme Charles M. Black (ORCID: https://orcid.org/0000-0001-8727-6592)
- David Romero-Bascones (ORCID: https://orcid.org/0000-0001-5394-2892)
- Cathy Egan
- Joseph Carroll (ORCID: https://orcid.org/0000-0002-8640-1029)
- Jugnoo Sangeeta Rahi (ORCID: https://orcid.org/0000-0002-5718-9209)
- Eoin O’Sullivan (ORCID: https://orcid.org/0000-0001-9380-1648)
- Tariq Aslam (ORCID: https://orcid.org/0009-0002-4528-8557)
- Jenny Barrett
- Robert Luben (ORCID: https://orcid.org/0000-0002-5088-6343)
- Ewan Birney (ORCID: https://orcid.org/0000-0001-8314-8497)
- Axel Petzold (ORCID: https://orcid.org/0000-0002-0344-9749)
- Jay Self (ORCID: https://orcid.org/0000-0002-1030-9963)
- Véronique Vitart (ORCID: https://orcid.org/0000-0002-4991-3797)
- Andrew John Lotery (ORCID: https://orcid.org/0000-0001-5541-4305)
- Thomas J. Littlejohns (ORCID: https://orcid.org/0000-0003-1177-6923)
- Savita Madhusudhan (ORCID: https://orcid.org/0000-0002-8203-0929)
- Alicja R. Rudnicka (ORCID: https://orcid.org/0000-0003-0369-8574)
- Dhanes Thomas (ORCID: https://orcid.org/0000-0003-3790-1163)
- Euan Paterson (ORCID: https://orcid.org/0000-0002-9693-1349)
- Maitane Barrenechea (ORCID: https://orcid.org/0000-0003-0149-6944)
- Tasanee Braithwaite (ORCID: https://orcid.org/0000-0002-3025-4066)
- Sarah Ennis (ORCID: https://orcid.org/0000-0001-6100-8573)
- Nikolas Pontikos (ORCID: https://orcid.org/0000-0003-1782-4711)
- Panagiotis I. Sergouniotis (ORCID: https://orcid.org/0000-0003-0986-4123)
- IRENE M. STRATTON (ORCID: https://orcid.org/0000-0003-1172-7865)
- Andrew Dick
- Sofia Torchia (ORCID: https://orcid.org/0009-0005-8861-5206)
- John Gallacher (ORCID: https://orcid.org/0000-0002-0995-5490)
- Cathy Williams
- Alexander Doney
- Anthony Khawaja
- Mike Weedon
- Bal Dhillon (ORCID: https://orcid.org/0000-0001-5993-0278)
- Zihan Sun (ORCID: https://orcid.org/0009-0001-2110-3856)
- Chris Owen
- Praveen Patel
- Heer N.V. Joisher
- DAVID STEEL
- Adam Lewandowski
- David Garway-Heath
- Gareth; id_orcid 0000-0001-8197-6280 McKay
- Paul Foster
- Robyn Tapp
- Naveed Sattar
- Tony Moore
- Nicholas Strouthidis
- Paul Bishop
- Katie Williams
- Richard Oram
- Sarah Barman
- Emanuele Trucco
- Max Yates
- Ananth Viswanathan
- Sharon Chua
- James Morgan
- Bernadette Mcguinness
- Ruth Hogg
- Naomi Allen
- Roxana Carare
- Peng Tee Khaw
- Sobha Sivaprasad
- Martin McKibbin
- Alison Hardcastle
- Jeremy Guggenheim
- Dr Sarah Mackie
- Dr Tom Macgillivray
- Dr Jay Self
- Prof Cathie Sudlow
- Alexander Day (ORCID: https://orcid.org/0000-0003-4926-7059)
- Yalin Zheng
- Phil Luthert
- Unai Ayala
- Jayne Woodside
- Adnan Tufail
- Tunde Peto
- Jane Gibson
- David J. Green
- Michelle Chan
Publication Details
- Journal
- Communications Biology
- Published
- 2026-11-03
- DOI
- https://doi.org/10.1038/s42003-026-11248-y
- Citations
- 1
- Primary Topic
- Retinal Diseases and Treatments
- Type
- article
- Field-Weighted Citation Impact
- 6.60
Funders
- Wellcome Trust
- National Eye Institute