Joint Associations of Diet, Lifestyle, and Genes with Age-Related Macular Degeneration

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. Interactions between healthy lifestyles AMD risk genotypes were studied in relation to the prevalenc...

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Published in:	Ophthalmology (Rochester, Minn.) Vol. 122; no. 11; p. 2286
Main Authors:	Meyers, Kristin J, Liu, Zhe, Millen, Amy E, Iyengar, Sudha K, Blodi, Barbara A, Johnson, Elizabeth, Snodderly, D Max, Klein, Michael L, Gehrs, Karen M, Tinker, Lesley, Sarto, Gloria E, Robinson, Jennifer, Wallace, Robert B, Mares, Julie A
Format:	Journal Article
Language:	English
Published:	United States 01.11.2015
Subjects:	Aged Alleles Complement Factor H - genetics Diet Feeding Behavior Female Genotyping Techniques Health Status Indicators Humans Life Style Lutein - blood Macular Degeneration - blood Macular Degeneration - genetics Macular Degeneration - prevention & control Middle Aged Odds Ratio Polymorphism, Single Nucleotide Prevalence Proteins - genetics Risk Factors Women's Health Zeaxanthins - blood
ISSN:	1549-4713, 1549-4713
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Abstract	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. Interactions between healthy lifestyles AMD risk genotypes were studied in relation to the prevalence of AMD, assessed 6 years later. Women 50 to 79 years of age in the Carotenoids in Age-Related Eye Disease Study with exposure and AMD data (n=1663). 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. 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. 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. 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.
AbstractList	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.PURPOSEUnhealthy 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.Interactions between healthy lifestyles AMD risk genotypes were studied in relation to the prevalence of AMD, assessed 6 years later.DESIGNInteractions between healthy lifestyles AMD risk genotypes were studied in relation to the prevalence of AMD, assessed 6 years later.Women 50 to 79 years of age in the Carotenoids in Age-Related Eye Disease Study with exposure and AMD data (n=1663).PARTICIPANTSWomen 50 to 79 years of age in the Carotenoids in Age-Related Eye Disease Study with exposure and AMD data (n=1663).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.METHODSHealthy 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.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.MAIN OUTCOME MEASURESAMD 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.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.RESULTSThe 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.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.CONCLUSIONSHaving 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. 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. Interactions between healthy lifestyles AMD risk genotypes were studied in relation to the prevalence of AMD, assessed 6 years later. Women 50 to 79 years of age in the Carotenoids in Age-Related Eye Disease Study with exposure and AMD data (n=1663). 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. 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. 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. 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.
Author	Liu, Zhe Snodderly, D Max Klein, Michael L Iyengar, Sudha K Wallace, Robert B Blodi, Barbara A Sarto, Gloria E Tinker, Lesley Millen, Amy E Mares, Julie A Meyers, Kristin J Johnson, Elizabeth Robinson, Jennifer Gehrs, Karen M
Author_xml	– sequence: 1 givenname: Kristin J surname: Meyers fullname: Meyers, Kristin J organization: Department of Ophthalmology and Visual Sciences, McPherson Eye Research Institute, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin – sequence: 2 givenname: Zhe surname: Liu fullname: Liu, Zhe organization: Department of Ophthalmology and Visual Sciences, McPherson Eye Research Institute, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin – sequence: 3 givenname: Amy E surname: Millen fullname: Millen, Amy E organization: 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 – sequence: 4 givenname: Sudha K surname: Iyengar fullname: Iyengar, Sudha K organization: Department of Epidemiology and Biostatistics, Case Western Reserve University, Cleveland, Ohio – sequence: 5 givenname: Barbara A surname: Blodi fullname: Blodi, Barbara A organization: Department of Ophthalmology and Visual Sciences, McPherson Eye Research Institute, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin – sequence: 6 givenname: Elizabeth surname: Johnson fullname: Johnson, Elizabeth organization: Jean Mayer USDA Human Nutrition, Research Center on Aging, Tufts University, Boston, Massachusetts – sequence: 7 givenname: D Max surname: Snodderly fullname: Snodderly, D Max organization: Department of Neuroscience, University of Texas, Austin, Texas – sequence: 8 givenname: Michael L surname: Klein fullname: Klein, Michael L organization: Casey Eye Institute, Department of Ophthalmology, Oregon Health & Science University, Portland, Oregon – sequence: 9 givenname: Karen M surname: Gehrs fullname: Gehrs, Karen M organization: Department of Ophthalmology & Visual Sciences, University of Iowa Hospital & Clinics, Iowa City, Iowa – sequence: 10 givenname: Lesley surname: Tinker fullname: Tinker, Lesley organization: Department of Cancer Prevention Research Program, Fred Hutchinson Cancer Research Center, Seattle, Washington – sequence: 11 givenname: Gloria E surname: Sarto fullname: Sarto, Gloria E organization: Department of Obstetrics & Gynecology, School of Medicine & Public Health, University of Wisconsin, Madison, Wisconsin – sequence: 12 givenname: Jennifer surname: Robinson fullname: Robinson, Jennifer organization: Department of Epidemiology, University of Iowa College of Public Health, Iowa City, Iowa – sequence: 13 givenname: Robert B surname: Wallace fullname: Wallace, Robert B organization: Department of Epidemiology, University of Iowa College of Public Health, Iowa City, Iowa – sequence: 14 givenname: Julie A surname: Mares fullname: Mares, Julie A email: jmarespe@wisc.edu organization: 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
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SubjectTerms	Aged Alleles Complement Factor H - genetics Diet Feeding Behavior Female Genotyping Techniques Health Status Indicators Humans Life Style Lutein - blood Macular Degeneration - blood Macular Degeneration - genetics Macular Degeneration - prevention & control Middle Aged Odds Ratio Polymorphism, Single Nucleotide Prevalence Proteins - genetics Risk Factors Women's Health Zeaxanthins - blood
Title	Joint Associations of Diet, Lifestyle, and Genes with Age-Related Macular Degeneration
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