Kristin J Meyers1, Zhe Liu1, Amy E Millen2, Sudha K Iyengar3, Barbara A Blodi1, Elizabeth Johnson4, D Max Snodderly5, Michael L Klein6, Karen M Gehrs7, Lesley Tinker8, Gloria E Sarto9, Jennifer Robinson10, Robert B Wallace10, Julie A Mares11. 1. Department of Ophthalmology and Visual Sciences, McPherson Eye Research Institute, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin. 2. 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. 3. Department of Epidemiology and Biostatistics, Case Western Reserve University, Cleveland, Ohio. 4. Jean Mayer USDA Human Nutrition, Research Center on Aging, Tufts University, Boston, Massachusetts. 5. Department of Neuroscience, University of Texas, Austin, Texas. 6. Casey Eye Institute, Department of Ophthalmology, Oregon Health & Science University, Portland, Oregon. 7. Department of Ophthalmology & Visual Sciences, University of Iowa Hospital & Clinics, Iowa City, Iowa. 8. Department of Cancer Prevention Research Program, Fred Hutchinson Cancer Research Center, Seattle, Washington. 9. Department of Obstetrics & Gynecology, School of Medicine & Public Health, University of Wisconsin, Madison, Wisconsin. 10. Department of Epidemiology, University of Iowa College of Public Health, Iowa City, Iowa. 11. 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.
Abstract
PURPOSE: 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. DESIGN: Interactions between healthy lifestyles AMD risk genotypes were studied in relation to the prevalence of AMD, assessed 6 years later. PARTICIPANTS: 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. MAIN OUTCOME MEASURES: 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.
PURPOSE: 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. DESIGN: Interactions between healthy lifestyles AMD risk genotypes were studied in relation to the prevalence of AMD, assessed 6 years later. PARTICIPANTS: 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. MAIN OUTCOME MEASURES: 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.
Authors: D Max Snodderly; Julie A Mares; Billy R Wooten; Lisa Oxton; Michael Gruber; Tara Ficek Journal: Invest Ophthalmol Vis Sci Date: 2004-02 Impact factor: 4.799
Authors: Julie A Mares; Rick P Voland; Sherie A Sondel; Amy E Millen; Tara Larowe; Suzen M Moeller; Mike L Klein; Barbara A Blodi; Richard J Chappell; Lesley Tinker; Cheryl Ritenbaugh; Karen M Gehrs; Gloria E Sarto; Elizabeth Johnson; D Max Snodderly; Robert B Wallace Journal: Arch Ophthalmol Date: 2010-12-13
Authors: Fernando Moreto; Hugo T Kano; Gabriel A Torezan; Erick P de Oliveira; Rodrigo M Manda; Okesley Teixeira; Edilaine Michelin; Camila R Correa; Roberto C Burini Journal: Diabetes Metab Syndr Date: 2015-04-25
Authors: Cathy C Laurie; Kimberly F Doheny; Daniel B Mirel; Elizabeth W Pugh; Laura J Bierut; Tushar Bhangale; Frederick Boehm; Neil E Caporaso; Marilyn C Cornelis; Howard J Edenberg; Stacy B Gabriel; Emily L Harris; Frank B Hu; Kevin B Jacobs; Peter Kraft; Maria Teresa Landi; Thomas Lumley; Teri A Manolio; Caitlin McHugh; Ian Painter; Justin Paschall; John P Rice; Kenneth M Rice; Xiuwen Zheng; Bruce S Weir Journal: Genet Epidemiol Date: 2010-09 Impact factor: 2.135
Authors: Maciej Tomaszewski; Fadi J Charchar; Malgorzata Przybycin; Lynne Crawford; A Michael Wallace; Katarzyna Gosek; Gordon D Lowe; Ewa Zukowska-Szczechowska; Wladyslaw Grzeszczak; Naveed Sattar; Anna F Dominiczak Journal: Arterioscler Thromb Vasc Biol Date: 2003-07-17 Impact factor: 8.311
Authors: Michael L Klein; Peter J Francis; Bernard Rosner; Robyn Reynolds; Sara C Hamon; Dennis W Schultz; Jurg Ott; Johanna M Seddon Journal: Ophthalmology Date: 2008-06 Impact factor: 12.079
Authors: Reecha Sofat; Juan P Casas; Andrew R Webster; Alan C Bird; Samantha S Mann; John R W Yates; Anthony T Moore; Tiina Sepp; Valentina Cipriani; Catey Bunce; Jane C Khan; Humma Shahid; Anand Swaroop; Gonçalo Abecasis; Kari E H Branham; Sepideh Zareparsi; Arthur A Bergen; Caroline C W Klaver; Dominique C Baas; Kang Zhang; Yuhong Chen; Daniel Gibbs; Bernhard H F Weber; Claudia N Keilhauer; Lars G Fritsche; Andrew Lotery; Angela J Cree; Helen L Griffiths; Shomi S Bhattacharya; Li L Chen; Sharon A Jenkins; Tunde Peto; Mark Lathrop; Thierry Leveillard; Michael B Gorin; Daniel E Weeks; Maria Carolina Ortube; Robert E Ferrell; Johanna Jakobsdottir; Yvette P Conley; Mati Rahu; Johan H Seland; Gisele Soubrane; Fotis Topouzis; Jesus Vioque; Laura Tomazzoli; Ian Young; John Whittaker; Usha Chakravarthy; Paulus T V M de Jong; Liam Smeeth; Astrid Fletcher; Aroon D Hingorani Journal: Int J Epidemiol Date: 2012-01-13 Impact factor: 7.196