Ming Ding1, Christina Ellervik2,3, Tao Huang4,5, Majken K Jensen1,6,7, Gary C Curhan6,7, Louis R Pasquale6,7,8, Jae H Kang6,7, Janey L Wiggs8, David J Hunter1,9,6,7, Walter C Willett1,9,6,7, Eric B Rimm1,9,6,7, Peter Kraft9,10, Daniel I Chasman2,11,12, Lu Qi1,13, Frank B Hu1,9,6,7, Qibin Qi14. 1. Departments of Nutrition. 2. Division of Preventive Medicine. 3. Department of Laboratory Medicine, Boston Children's Hospital, Boston, MA. 4. Epidemiology Domain, Saw Swee Hock School of Public Health, National University of Singapore, Singapore. 5. Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore. 6. Channing Division of Network Medicine. 7. Harvard Medical School, Boston, MA. 8. Department of Ophthalmology, Mass Eye and Ear Infirmary, Harvard Medical School, Boston, MA. 9. Epidemiology. 10. Biostatistics, Harvard TH Chan School of Public Health, Boston, MA. 11. Division of Genetics, Brigham and Women's Hospital, Boston, MA. 12. Broad Institute of MIT and Harvard, Cambridge, MA. 13. Department of Epidemiology, School of Public Health and Tropical Medicine, Tulane University, New Orleans, LA. 14. Department of Epidemiology & Population Health, Albert Einstein College of Medicine, Bronx, NY.
Abstract
Background: It is unknown whether dietary quality modifies genetic association with body mass index (BMI). Objective: This study examined whether dietary quality modifies genetic association with BMI. Design: We calculated 3 diet quality scores including the Alternative Healthy Eating Index 2010 (AHEI-2010), the Alternative Mediterranean Diet score (AMED), and the Dietary Approach to Stop Hypertension (DASH) diet score. We examined the interactions of a genetic risk score (GRS) based on 97 BMI-associated variants with the 3 diet quality scores on BMI in 30,904 participants from 3 large cohorts. Results: We found significant interactions between total GRS and all 3 diet scores on BMI assessed after 2-3 y, with an attenuated genetic effect observed in individuals with healthier diets (AHEI: P-interaction = 0.003; AMED: P = 0.001; DASH: P = 0.004). For example, the difference in BMI (kg/m2) per 10-unit increment of the GRS was smaller among participants in the highest tertile of AHEI score compared with those in the lowest tertile (0.84; 95% CI: 0.72, 0.96 compared with 1.14; 95% CI: 0.99, 1.29). Results were consistent across the 3 cohorts with no significant heterogeneity. The interactions with diet scores on BMI appeared more significant for central nervous system GRSs (P < 0.01 for 3 diet scores) than for non-central nervous system GRSs (P > 0.05 for 3 diet scores). Conclusions: A higher diet quality attenuated genetic predisposition to obesity. These findings underscore the importance of maintaining a healthful diet for the prevention of obesity, particularly for those individuals with a strong genetic predisposition to obesity. This trial was registered with the Clinical Trial Registry as NCT03577639.
Background: It is unknown whether dietary quality modifies genetic association with body mass index (BMI). Objective: This study examined whether dietary quality modifies genetic association with BMI. Design: We calculated 3 diet quality scores including the Alternative Healthy Eating Index 2010 (AHEI-2010), the Alternative Mediterranean Diet score (AMED), and the Dietary Approach to Stop Hypertension (DASH) diet score. We examined the interactions of a genetic risk score (GRS) based on 97 BMI-associated variants with the 3 diet quality scores on BMI in 30,904 participants from 3 large cohorts. Results: We found significant interactions between total GRS and all 3 diet scores on BMI assessed after 2-3 y, with an attenuated genetic effect observed in individuals with healthier diets (AHEI: P-interaction = 0.003; AMED: P = 0.001; DASH: P = 0.004). For example, the difference in BMI (kg/m2) per 10-unit increment of the GRS was smaller among participants in the highest tertile of AHEI score compared with those in the lowest tertile (0.84; 95% CI: 0.72, 0.96 compared with 1.14; 95% CI: 0.99, 1.29). Results were consistent across the 3 cohorts with no significant heterogeneity. The interactions with diet scores on BMI appeared more significant for central nervous system GRSs (P < 0.01 for 3 diet scores) than for non-central nervous system GRSs (P > 0.05 for 3 diet scores). Conclusions: A higher diet quality attenuated genetic predisposition to obesity. These findings underscore the importance of maintaining a healthful diet for the prevention of obesity, particularly for those individuals with a strong genetic predisposition to obesity. This trial was registered with the Clinical Trial Registry as NCT03577639.
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