Joint Contribution of Genetic Susceptibility and Modifiable Factors to the Progression of Age-Related Macular Degeneration over 10 Years: The Three Continent AMD Consortium Report

Nichole Joachim; Annette Kifley; Johanna Maria Colijn; Kristine E Lee; Gabriëlle H S Buitendijk; Barbara E K Klein; Chelsea Myers; Stacy M Meuer; Ava G Tan; Victoria Flood; Josje D Schoufour; Oscar H Franco; Elizabeth G Holliday; John Attia; Gerald Liew; Sudha K Iyengar; Paulus T V M de Jong; Albert Hofman; Johannes R Vingerling; Paul Mitchell; Ronald Klein; Caroline C W Klaver; Jie Jin Wang

doi:10.1016/j.oret.2017.10.019

Joint Contribution of Genetic Susceptibility and Modifiable Factors to the Progression of Age-Related Macular Degeneration over 10 Years: The Three Continent AMD Consortium Report

Ophthalmol Retina. 2018 Jul;2(7):684-693. doi: 10.1016/j.oret.2017.10.019. Epub 2017 Dec 30.

Authors

Nichole Joachim¹, Annette Kifley¹, Johanna Maria Colijn², Kristine E Lee³, Gabriëlle H S Buitendijk², Barbara E K Klein³, Chelsea Myers³, Stacy M Meuer³, Ava G Tan¹, Victoria Flood⁴, Josje D Schoufour⁵, Oscar H Franco⁵, Elizabeth G Holliday⁶, John Attia⁷, Gerald Liew¹, Sudha K Iyengar⁸, Paulus T V M de Jong⁹, Albert Hofman¹⁰, Johannes R Vingerling¹¹, Paul Mitchell¹, Ronald Klein³, Caroline C W Klaver², Jie Jin Wang¹²

Affiliations

¹ Centre for Vision Research, Westmead Institute for Medical Research, University of Sydney, Sydney, Australia.
² Department of Ophthalmology, Erasmus Medical Center, Rotterdam, The Netherlands; Department of Epidemiology, Erasmus Medical Center, Rotterdam, The Netherlands.
³ Department of Ophthalmology & Visual Sciences, University of Wisconsin Medical School, Madison, Wisconsin.
⁴ Faculty of Health Sciences, University of Sydney, Sydney, Australia; Western Sydney Local Health District, Westmead, Australia.
⁵ Department of Epidemiology, Erasmus Medical Center, Rotterdam, The Netherlands.
⁶ Centre for Clinical Epidemiology and Biostatistics and School of Medicine and Public Health, University of Newcastle, Newcastle, Australia.
⁷ Centre for Clinical Epidemiology and Biostatistics and School of Medicine and Public Health, University of Newcastle, Newcastle, Australia; Department of Medicine, John Hunter Hospital and Hunter Medical Research Institute, Newcastle, Australia.
⁸ Department of Epidemiology and Biostatistics, Case Western Reserve University, Cleveland, Ohio.
⁹ Netherlands Institute of Neurosciences, Institute of the Royal Netherlands Academy of Arts and Sciences, Department of Ophthalmology, Academic Medical Centre, Amsterdam, and Leiden University Medical Centre, Leiden, The Netherlands.
¹⁰ Department of Epidemiology, Erasmus Medical Center, Rotterdam, The Netherlands; Netherlands Consortium for Healthy Aging, Netherlands Genomics Initiative, The Hague, The Netherlands.
¹¹ Department of Ophthalmology, Erasmus Medical Center, Rotterdam, The Netherlands; Department of Epidemiology, Erasmus Medical Center, Rotterdam, The Netherlands; Department of Ophthalmology, Radboud University Medical Centre, Nijmegen, The Netherlands.
¹² Centre for Vision Research, Westmead Institute for Medical Research, University of Sydney, Sydney, Australia; Office of Clinical Sciences and Academic Medicine Research Institute, Duke-NUS, Singapore, Republic of Singapore. Electronic address: jiejin.wang@sydney.edu.au.

PMID: 31047378
DOI: 10.1016/j.oret.2017.10.019

Abstract

Purpose: To assess joint effects of genetic and modifiable factors on the 10-year progression of age-related macular degeneration (AMD).

Design: Individual and pooled data analyses of 2 population-based cohorts.

Participants: Blue Mountains Eye Study (BMES) and Rotterdam Study (RS) participants (n = 835).

Methods: Participants of the BMES and RS were followed up over 10 years or more. At baseline and follow-up visits, interviews using questionnaires and eye examinations with retinal photography were performed. Age-related macular degeneration was assessed by trained photographic graders and verified by retinal specialists. Genetic susceptibility to AMD meant carrying 2 or more risk alleles of the CFH or ARMS2 SNPs, or both (rs1061170 and rs10490924), relative to 0 or 1 risk allele. Discrete logistic regression models were used to investigate the joint associations of genetic susceptibility and either smoking, fish consumption, dietary intake of lutein-zeaxanthin, or combined environmental risk scores from the 3 modifiable factors with the risk of AMD progression. Odds ratios (ORs) with 95% confidence intervals (CIs) and synergy indexes are reported.

Main outcome measure: Ten-year progression of AMD, categorized as any (≥1 step) or 2-step (≥2 steps) progression on the Three Continent AMD Consortium 5-step severity scale.

Results: Older age, the presence of AMD genetic susceptibility, and baseline AMD status were associated strongly with AMD progression (P < 0.0001). In analyses of pooled data, each additional score from the combined environmental risk scores was associated with an increased risk of 2-step progression over 10 years (OR, 1.26; 95% CI, 1.02-1.56). The copresence of AMD genetic susceptibility and combined risk score of 3 or more was associated with a substantially higher risk of 2-step progression compared with the presence of either factor alone. There was a significant synergistic effect (OR, 4.14; 95% CI, 1.07-15.95) and interaction (P = 0.025) between genetic susceptibility and environmental risk score of 3 or more.

Conclusions: Among persons with AMD genetic susceptibility and pre-existing early AMD lesions, presenting with high environmental risk scores from 3 modifiable factors (smoking, infrequent consumption of fish, low lutein-zeaxanthin intake) were associated with an increased risk of 2-step progression over 10 years.