Polygenic scores, diet quality, and type 2 diabetes risk: An observational study among 35,759 adults from 3 US cohorts

<h4>Background</h4> Both genetic and lifestyle factors contribute to the risk of type 2 diabetes, but the extent to which there is a synergistic effect of the 2 factors is unclear. The aim of this study was to examine the joint associations of genetic risk and diet quality with incident...

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Main Authors: Jordi Merino, Marta Guasch-Ferré, Jun Li, Wonil Chung, Yang Hu, Baoshan Ma, Yanping Li, Jae H. Kang, Peter Kraft, Liming Liang, Qi Sun, Paul W. Franks, JoAnn E. Manson, Walter C. Willet, Jose C. Florez, Frank B. Hu
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2022-04-01
Series:PLoS Medicine
Online Access:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9041832/?tool=EBI
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author Jordi Merino
Marta Guasch-Ferré
Jun Li
Wonil Chung
Yang Hu
Baoshan Ma
Yanping Li
Jae H. Kang
Peter Kraft
Liming Liang
Qi Sun
Paul W. Franks
JoAnn E. Manson
Walter C. Willet
Jose C. Florez
Frank B. Hu
author_facet Jordi Merino
Marta Guasch-Ferré
Jun Li
Wonil Chung
Yang Hu
Baoshan Ma
Yanping Li
Jae H. Kang
Peter Kraft
Liming Liang
Qi Sun
Paul W. Franks
JoAnn E. Manson
Walter C. Willet
Jose C. Florez
Frank B. Hu
author_sort Jordi Merino
collection DOAJ
description <h4>Background</h4> Both genetic and lifestyle factors contribute to the risk of type 2 diabetes, but the extent to which there is a synergistic effect of the 2 factors is unclear. The aim of this study was to examine the joint associations of genetic risk and diet quality with incident type 2 diabetes. <h4>Methods and findings</h4> We analyzed data from 35,759 men and women in the United States participating in the Nurses’ Health Study (NHS) I (1986 to 2016) and II (1991 to 2017) and the Health Professionals Follow-up Study (HPFS; 1986 to 2016) with available genetic data and who did not have diabetes, cardiovascular disease, or cancer at baseline. Genetic risk was characterized using both a global polygenic score capturing overall genetic risk and pathway-specific polygenic scores denoting distinct pathophysiological mechanisms. Diet quality was assessed using the Alternate Healthy Eating Index (AHEI). Cox models were used to calculate hazard ratios (HRs) for type 2 diabetes after adjusting for potential confounders. With over 902,386 person-years of follow-up, 4,433 participants were diagnosed with type 2 diabetes. The relative risk of type 2 diabetes was 1.29 (95% confidence interval [CI] 1.25, 1.32; P < 0.001) per standard deviation (SD) increase in global polygenic score and 1.13 (1.09, 1.17; P < 0.001) per 10-unit decrease in AHEI. Irrespective of genetic risk, low diet quality, as compared to high diet quality, was associated with approximately 30% increased risk of type 2 diabetes (Pinteraction = 0.69). The joint association of low diet quality and increased genetic risk was similar to the sum of the risk associated with each factor alone (Pinteraction = 0.30). Limitations of this study include the self-report of diet information and possible bias resulting from inclusion of highly educated participants with available genetic data. <h4>Conclusions</h4> These data provide evidence for the independent associations of genetic risk and diet quality with incident type 2 diabetes and suggest that a healthy diet is associated with lower diabetes risk across all levels of genetic risk. In an observational study of 3 cohorts in the United States, Jordi Merino, Marta Guasch-Ferré, Jun Li, and colleagues investigate the individual and combined associations between genetic risk, diet quality, and risk of type 2 diabetes. Author summary <h4>Why was this study done?</h4> Both genetic and lifestyle factors contribute to individual-level risk of type 2 diabetes. While previous studies have shown that adherence to a healthy lifestyle is associated with reduced risk of type 2 diabetes regardless of genetic risk, the partial characterization of genetic risk and the predominant assessment of interactions on the multiplicative scale might have prevented previous studies from identifying genetic profiles interacting with dietary exposures. Therefore, understanding how genetic risk and diet quality contribute to the development of type 2 diabetes is important to support evidence-based preventive interventions. <h4>What did the researchers do and find?</h4> In 3 cohort studies involving 35,759 men and women in the US, we used novel polygenic scores for type 2 diabetes to systematically evaluate the presence of additive and multiplicative interactions between genetic risk and diet quality on the development of type 2 diabetes. We found that both low diet quality and increased overall or pathway-specific genetic risk were independently associated with higher risk of type 2 diabetes. We documented that within any genetic risk category, high diet quality, as compared to low diet quality, was associated with a nearly 30% lower risk of type 2 diabetes. Further, we showed that the risk of type 2 diabetes attributed to the combination of increased genetic risk and low diet quality was similar to the sum of the risks associated with each factor alone. <h4>What do these findings mean?</h4> Results from this study suggest that consuming a healthier diet is associated with a lower risk of type 2 diabetes regardless of genetic risk. Our results underscore the value of genetic risk assessment to identify individuals at increased disease risk and their potential for risk stratification and surveillance. Such knowledge can serve to inform and design future strategies to advance the prevention of type 2 diabetes.
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spelling doaj.art-e8b9f8f460bc4c518376ae5e7aef85722022-12-22T01:06:05ZengPublic Library of Science (PLoS)PLoS Medicine1549-12771549-16762022-04-01194Polygenic scores, diet quality, and type 2 diabetes risk: An observational study among 35,759 adults from 3 US cohortsJordi MerinoMarta Guasch-FerréJun LiWonil ChungYang HuBaoshan MaYanping LiJae H. KangPeter KraftLiming LiangQi SunPaul W. FranksJoAnn E. MansonWalter C. WilletJose C. FlorezFrank B. Hu<h4>Background</h4> Both genetic and lifestyle factors contribute to the risk of type 2 diabetes, but the extent to which there is a synergistic effect of the 2 factors is unclear. The aim of this study was to examine the joint associations of genetic risk and diet quality with incident type 2 diabetes. <h4>Methods and findings</h4> We analyzed data from 35,759 men and women in the United States participating in the Nurses’ Health Study (NHS) I (1986 to 2016) and II (1991 to 2017) and the Health Professionals Follow-up Study (HPFS; 1986 to 2016) with available genetic data and who did not have diabetes, cardiovascular disease, or cancer at baseline. Genetic risk was characterized using both a global polygenic score capturing overall genetic risk and pathway-specific polygenic scores denoting distinct pathophysiological mechanisms. Diet quality was assessed using the Alternate Healthy Eating Index (AHEI). Cox models were used to calculate hazard ratios (HRs) for type 2 diabetes after adjusting for potential confounders. With over 902,386 person-years of follow-up, 4,433 participants were diagnosed with type 2 diabetes. The relative risk of type 2 diabetes was 1.29 (95% confidence interval [CI] 1.25, 1.32; P < 0.001) per standard deviation (SD) increase in global polygenic score and 1.13 (1.09, 1.17; P < 0.001) per 10-unit decrease in AHEI. Irrespective of genetic risk, low diet quality, as compared to high diet quality, was associated with approximately 30% increased risk of type 2 diabetes (Pinteraction = 0.69). The joint association of low diet quality and increased genetic risk was similar to the sum of the risk associated with each factor alone (Pinteraction = 0.30). Limitations of this study include the self-report of diet information and possible bias resulting from inclusion of highly educated participants with available genetic data. <h4>Conclusions</h4> These data provide evidence for the independent associations of genetic risk and diet quality with incident type 2 diabetes and suggest that a healthy diet is associated with lower diabetes risk across all levels of genetic risk. In an observational study of 3 cohorts in the United States, Jordi Merino, Marta Guasch-Ferré, Jun Li, and colleagues investigate the individual and combined associations between genetic risk, diet quality, and risk of type 2 diabetes. Author summary <h4>Why was this study done?</h4> Both genetic and lifestyle factors contribute to individual-level risk of type 2 diabetes. While previous studies have shown that adherence to a healthy lifestyle is associated with reduced risk of type 2 diabetes regardless of genetic risk, the partial characterization of genetic risk and the predominant assessment of interactions on the multiplicative scale might have prevented previous studies from identifying genetic profiles interacting with dietary exposures. Therefore, understanding how genetic risk and diet quality contribute to the development of type 2 diabetes is important to support evidence-based preventive interventions. <h4>What did the researchers do and find?</h4> In 3 cohort studies involving 35,759 men and women in the US, we used novel polygenic scores for type 2 diabetes to systematically evaluate the presence of additive and multiplicative interactions between genetic risk and diet quality on the development of type 2 diabetes. We found that both low diet quality and increased overall or pathway-specific genetic risk were independently associated with higher risk of type 2 diabetes. We documented that within any genetic risk category, high diet quality, as compared to low diet quality, was associated with a nearly 30% lower risk of type 2 diabetes. Further, we showed that the risk of type 2 diabetes attributed to the combination of increased genetic risk and low diet quality was similar to the sum of the risks associated with each factor alone. <h4>What do these findings mean?</h4> Results from this study suggest that consuming a healthier diet is associated with a lower risk of type 2 diabetes regardless of genetic risk. Our results underscore the value of genetic risk assessment to identify individuals at increased disease risk and their potential for risk stratification and surveillance. Such knowledge can serve to inform and design future strategies to advance the prevention of type 2 diabetes.https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9041832/?tool=EBI
spellingShingle Jordi Merino
Marta Guasch-Ferré
Jun Li
Wonil Chung
Yang Hu
Baoshan Ma
Yanping Li
Jae H. Kang
Peter Kraft
Liming Liang
Qi Sun
Paul W. Franks
JoAnn E. Manson
Walter C. Willet
Jose C. Florez
Frank B. Hu
Polygenic scores, diet quality, and type 2 diabetes risk: An observational study among 35,759 adults from 3 US cohorts
PLoS Medicine
title Polygenic scores, diet quality, and type 2 diabetes risk: An observational study among 35,759 adults from 3 US cohorts
title_full Polygenic scores, diet quality, and type 2 diabetes risk: An observational study among 35,759 adults from 3 US cohorts
title_fullStr Polygenic scores, diet quality, and type 2 diabetes risk: An observational study among 35,759 adults from 3 US cohorts
title_full_unstemmed Polygenic scores, diet quality, and type 2 diabetes risk: An observational study among 35,759 adults from 3 US cohorts
title_short Polygenic scores, diet quality, and type 2 diabetes risk: An observational study among 35,759 adults from 3 US cohorts
title_sort polygenic scores diet quality and type 2 diabetes risk an observational study among 35 759 adults from 3 us cohorts
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9041832/?tool=EBI
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