Joint Associations of Diet, Lifestyle, and Genes with Age-Related Macular Degeneration.
OBJECTIVE
Unhealthy lifestyles have been associated with increased odds for age-related macular degeneration (AMD). Whether this association is modified by genetic risk for AMD is unknown and was investigated.


METHODS
Interactions between healthy lifestyles AMD risk genotypes were studied in relation to the prevalence of AMD, assessed 6 years later.


METHODS
Women 50 to 79 years of age in the Carotenoids in Age-Related Eye Disease Study with exposure and AMD data (n=1663).


METHODS
Healthy lifestyle scores (0-6 points) were assigned based on Healthy Eating Index scores, physical activity (metabolic equivalent of task hours/week), and smoking pack years assessed in 1994 and 1998. Genetic risk was based on Y402H in complement factor H (CFH) and A69S in age-related maculopathy susceptibility locus 2 (ARMS2). Additive and multiplicative interactions in odds ratios were assessed using the synergy index and a multiplicative interaction term, respectively.


METHODS
AMD presence and severity were assessed from grading of stereoscopic fundus photographs taken in 2001-2004. AMD was present in 337 women, 91% of whom had early AMD.


RESULTS
The odds of AMD were 3.3 times greater (95% confidence interval [CI], 1.8-6.1) in women with both low healthy lifestyle score (0-2) and high-risk CFH genotype (CC), relative to those who had low genetic risk (TT) and high healthy lifestyle scores (4-6). There were no significant additive (synergy index [SI], 1.08; 95% CI, 0.70-1.67) or multiplicative (Pinteraction=0.94) interactions in the full sample. However, when limiting the sample to women with stable diets before AMD assessment (n=728) the odds for AMD associated with low healthy lifestyle scores and high-risk CFH genotype were strengthened (odds ratio, 4.6; 95% CI, 1.8-11.6) and the synergy index was significant (SI, 1.34; 95% CI, 1.05-1.70). Adjusting for dietary lutein and zeaxanthin attenuated, and therefore partially explained, the joint association. There were no significant additive or multiplicative interactions for ARMS2 and lifestyle score.


CONCLUSIONS
Having unhealthy lifestyles and 2 CFH risk alleles increased AMD risk (primarily in the early stages), in an or additive or greater (synergistic) manner. However, unhealthy lifestyles increased AMD risk regardless of AMD risk genotype.
Department of Ophthalmology and Visual Sciences, McPherson Eye Research Institute, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin.
Kristin J
KJ
Meyers
Department of Ophthalmology and Visual Sciences, McPherson Eye Research Institute, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin.
Zhe
Z
Liu
Department of Epidemiology and Environmental Health, School of Public Health and Health Professions, University at Buffalo, The State University of New York, Buffalo, New York.
Amy E
AE
Millen
Department of Epidemiology and Biostatistics, Case Western Reserve University, Cleveland, Ohio.
Sudha K
SK
Iyengar
Department of Ophthalmology and Visual Sciences, McPherson Eye Research Institute, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin.
Barbara A
BA
Blodi
Jean Mayer USDA Human Nutrition, Research Center on Aging, Tufts University, Boston, Massachusetts.
Elizabeth
E
Johnson
Department of Neuroscience, University of Texas, Austin, Texas.
D Max
DM
Snodderly
Casey Eye Institute, Department of Ophthalmology, Oregon Health & Science University, Portland, Oregon.
Michael L
ML
Klein
Department of Ophthalmology & Visual Sciences, University of Iowa Hospital & Clinics, Iowa City, Iowa.
Karen M
KM
Gehrs
Department of Cancer Prevention Research Program, Fred Hutchinson Cancer Research Center, Seattle, Washington.
Lesley
L
Tinker
Department of Obstetrics & Gynecology, School of Medicine & Public Health, University of Wisconsin, Madison, Wisconsin.
Gloria E
GE
Sarto
Department of Epidemiology, University of Iowa College of Public Health, Iowa City, Iowa.
Jennifer
J
Robinson
Department of Epidemiology, University of Iowa College of Public Health, Iowa City, Iowa.
Robert B
RB
Wallace
Department of Ophthalmology and Visual Sciences, McPherson Eye Research Institute, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin. Electronic address: jmarespe@wisc.edu.
Julie A
JA
Mares
D000368:Aged; D000483:Alleles; D017242:Complement Factor H / Q000235:genetics; D004032:Diet; D005247:Feeding Behavior; D005260:Female; D060005:Genotyping Techniques; D006305:Health Status Indicators; D006801:Humans; D008019:Life Style; D014975:Lutein / Q000097:blood; D008268:Macular Degeneration / Q000097:blood / Q000235:genetics* / Q000517:prevention & control; D008875:Middle Aged; D016017:Odds Ratio; D020641:Polymorphism, Single Nucleotide; D015995:Prevalence; D011506:Proteins / Q000235:genetics; D012307:Risk Factors; D016387:Women's Health; D065146:Zeaxanthins / Q000097:blood
C514392:ARMS2 protein, human; C493495:CFH protein, human; D011506:Proteins; D065146:Zeaxanthins; D017242:Complement Factor H; D014975:Lutein