title: Genetic susceptibility, dietary antioxidants, and long-term incidence of age-related macular degeneration in two populations.
abstract: OBJECTIVE
  To examine effect modification between genetic susceptibility to age-related macular degeneration (AMD) and dietary antioxidant or fish consumption on AMD risk.
  
  
  METHODS
  Pooled data analysis of population-based cohorts.
  
  
  METHODS
  Participants from the Blue Mountains Eye Study (BMES) and Rotterdam Study (RS).
  
  
  METHODS
  Dietary intakes of antioxidants (lutein/zeaxanthin [LZ], β-carotene, and vitamin C), long-chain omega-3 polyunsaturated fatty acids, and zinc were estimated from food frequency questionnaires. The AMD genetic risk was classified according to the number of risk alleles of CFH (rs1061170) or ARMS2 (rs10490924) as low (no or 1 risk allele) or high (≥ 2 risk alleles). Interactions between dietary intake and genetic risk levels were assessed. Associations between dietary intake and AMD risk were assessed comparing the highest with the 2 lower intake tertiles by genetic risk subgroups using discrete logistic regression, conducted in each study separately and then using pooled data. Participants without AMD lesions at any visit were controls. We adjusted for age and sex in analyses of each cohort sample and for smoking status and study site in pooled-data analyses.
  
  
  METHODS
  All 15-year incident late AMD cases were confirmed by chief investigators of the Beaver Dam Eye Study, BMES, and RS. Intergrader reproducibility was assessed in an early AMD subsample, with 86.4% agreement between BMES and RS graders, allowing for a 1-step difference on a 5-step AMD severity scale.
  
  
  RESULTS
  In pooled data analyses, we found significant interaction between AMD genetic risk status and LZ intake (P=0.0009) but nonsignificant interactions between genetic risk status and weekly fish consumption (P=0.05) for risk of any AMD. Among participants with high genetic risk, the highest intake tertile of LZ was associated with a >20% reduced risk of early AMD, and weekly consumption of fish was associated with a 40% reduced risk of late AMD. No similar association was evident among participants with low genetic risk. No interaction was detected between β-carotene or vitamin C and genetic risk status.
  
  
  CONCLUSIONS
  Protection against AMD from greater LZ and fish consumption in persons with high genetic risk based on 2 major AMD genes raises the possibility of personalized preventive interventions.
authors.affiliation: Centre for Vision Research, Department of Ophthalmology and the Westmead Millennium Institute, University of Sydney, Sydney, Australia; Centre for Eye Research Australia, University of Melbourne, Royal Victorian Eye and Ear Hospital, Melbourne, Australia. Electronic address: jiejin.wang@sydney.edu.au.
authors.forename: Jie Jin
authors.initials: JJ
authors.lastname: Wang
authors.affiliation: Department of Ophthalmology, Erasmus Medical Center, Rotterdam, The Netherlands; Department of Epidemiology, Erasmus Medical Center, Rotterdam, The Netherlands.
authors.forename: Gabriëlle H S
authors.initials: GH
authors.lastname: Buitendijk
authors.affiliation: Centre for Vision Research, Department of Ophthalmology and the Westmead Millennium Institute, University of Sydney, Sydney, Australia.
authors.forename: Elena
authors.initials: E
authors.lastname: Rochtchina
authors.affiliation: Department of Ophthalmology, Erasmus Medical Center, Rotterdam, The Netherlands.
authors.forename: Kristine E
authors.initials: KE
authors.lastname: Lee
authors.affiliation: Department of Ophthalmology and Visual Sciences, University of Wisconsin Medical School, Madison, Wisconsin.
authors.forename: Barbara E K
authors.initials: BE
authors.lastname: Klein
authors.affiliation: Department of Epidemiology, Erasmus Medical Center, Rotterdam, The Netherlands.
authors.forename: Cornelia M
authors.initials: CM
authors.lastname: van Duijn
authors.affiliation: Faculty of Health and Behavioural Sciences, University of Wollongong, Wollongong, Australia.
authors.forename: Victoria M
authors.initials: VM
authors.lastname: Flood
authors.affiliation: Department of Ophthalmology and Visual Sciences, University of Wisconsin Medical School, Madison, Wisconsin.
authors.forename: Stacy M
authors.initials: SM
authors.lastname: Meuer
authors.affiliation: 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.
authors.forename: John
authors.initials: J
authors.lastname: Attia
authors.affiliation: Department of Ophthalmology and Visual Sciences, University of Wisconsin Medical School, Madison, Wisconsin.
authors.forename: Chelsea
authors.initials: C
authors.lastname: Myers
authors.affiliation: Centre for Clinical Epidemiology and Biostatistics, and School of Medicine and Public Health, University of Newcastle, Newcastle, Australia.
authors.forename: Elizabeth G
authors.initials: EG
authors.lastname: Holliday
authors.affiliation: Centre for Vision Research, Department of Ophthalmology and the Westmead Millennium Institute, University of Sydney, Sydney, Australia.
authors.forename: Ava G
authors.initials: AG
authors.lastname: Tan
authors.affiliation: School of Medicine and Public Health, University of Newcastle, Newcastle, Australia; School of Public Health, Sydney Medical School, University of Sydney, Sydney, Australia.
authors.forename: Wayne T
authors.initials: WT
authors.lastname: Smith
authors.affiliation: Department of Epidemiology and Biostatistics, Case Western Reserve University, Cleveland, Ohio.
authors.forename: Sudha K
authors.initials: SK
authors.lastname: Iyengar
authors.affiliation: Netherlands Institute of Neurosciences, Institute of the Royal Netherlands Academy of Arts and Sciences, Department of Ophthalmology, AMC, Amsterdam, and Department of Ophthalmology, LUMC, Leiden, The Netherlands.
authors.forename: Paulus T V M
authors.initials: PT
authors.lastname: de Jong
authors.affiliation: Department of Epidemiology, Erasmus Medical Center, Rotterdam, The Netherlands; Netherlands Consortium for Healthy Aging, Netherlands Genomics Initiative, the Hague, The Netherlands.
authors.forename: Albert
authors.initials: A
authors.lastname: Hofman
authors.affiliation: Department of Ophthalmology, Erasmus Medical Center, Rotterdam, The Netherlands; Department of Epidemiology, Erasmus Medical Center, Rotterdam, The Netherlands.
authors.forename: Johannes R
authors.initials: JR
authors.lastname: Vingerling
authors.affiliation: Centre for Vision Research, Department of Ophthalmology and the Westmead Millennium Institute, University of Sydney, Sydney, Australia.
authors.forename: Paul
authors.initials: P
authors.lastname: Mitchell
authors.affiliation: Department of Ophthalmology and Visual Sciences, University of Wisconsin Medical School, Madison, Wisconsin.
authors.forename: Ronald
authors.initials: R
authors.lastname: Klein
authors.affiliation: Department of Ophthalmology, Erasmus Medical Center, Rotterdam, The Netherlands; Department of Epidemiology, Erasmus Medical Center, Rotterdam, The Netherlands.
authors.forename: Caroline C W
authors.initials: CC
authors.lastname: Klaver
mesh_terms: D000368:Aged; D000975:Antioxidants / Q000008:administration & dosage*; D001205:Ascorbic Acid / Q000008:administration & dosage; D017242:Complement Factor H / Q000235:genetics; D004032:Diet; D015525:Fatty Acids, Omega-3 / Q000008:administration & dosage; D005247:Feeding Behavior; D005260:Female; D005396:Fish Products; D005638:Fruit; D020022:Genetic Predisposition to Disease; D060005:Genotyping Techniques; D006801:Humans; D015994:Incidence; D014975:Lutein / Q000008:administration & dosage; D008268:Macular Degeneration / Q000453:epidemiology* / Q000235:genetics* / Q000517:prevention & control; D008297:Male; D008875:Middle Aged; D017720:Molecular Epidemiology; D009426:Netherlands / Q000453:epidemiology; D009517:New South Wales / Q000453:epidemiology; D011506:Proteins / Q000235:genetics; D011795:Surveys and Questionnaires; D014675:Vegetables; D024341:Xanthophylls / Q000008:administration & dosage; D065146:Zeaxanthins; D017967:Zinc Compounds / Q000008:administration & dosage; D019207:beta Carotene / Q000008:administration & dosage
chemical_list: C514392:ARMS2 protein, human; D000975:Antioxidants; C493495:CFH protein, human; D015525:Fatty Acids, Omega-3; D011506:Proteins; D024341:Xanthophylls; D065146:Zeaxanthins; D017967:Zinc Compounds; D019207:beta Carotene; D017242:Complement Factor H; D001205:Ascorbic Acid; D014975:Lutein