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Improving adherence to healthy dietary patterns, genetic risk, and long term weight gain: gene-diet interaction analysis in two prospective cohort studies

BMJ 2018; 360 doi: (Published 10 January 2018) Cite this as: BMJ 2018;360:j5644
  1. Tiange Wang, research fellow1 2,
  2. Yoriko Heianza, research fellow1,
  3. Dianjianyi Sun, research fellow1,
  4. Tao Huang, research fellow3,
  5. Wenjie Ma, research fellow4,
  6. Eric B Rimm, professor4 5 6,
  7. JoAnn E Manson, professor4 6 7,
  8. Frank B Hu, professor5 6,
  9. Walter C Willett, professor4 5 6,
  10. Lu Qi, professor1 5 6
  1. 1Department of Epidemiology, School of Public Health and Tropical Medicine, Tulane University, New Orleans, LA 70112, USA
  2. 2Shanghai Institute of Endocrine and Metabolic Diseases, Rui Jin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
  3. 3Department of Epidemiology and Biostatistics, School of Public Health, Peking University Health Science Center, Beijing, China
  4. 4Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, USA
  5. 5Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, MA, USA
  6. 6Channing Division of Network Medicine, Department of Medicine, Brigham and Women’s Hospital and Harvard Medical School, Boston, MA, USA
  7. 7Division of Preventive Medicine, Department of Medicine, Brigham and Women’s Hospital and Harvard Medical School, Boston, MA, USA
  1. Correspondence to: L Qi lqi1{at}
  • Accepted 29 November 2017


Objective To investigate whether improving adherence to healthy dietary patterns interacts with the genetic predisposition to obesity in relation to long term changes in body mass index and body weight.

Design Prospective cohort study.

Setting Health professionals in the United States.

Participants 8828 women from the Nurses’ Health Study and 5218 men from the Health Professionals Follow-up Study.

Exposure Genetic predisposition score was calculated on the basis of 77 variants associated with body mass index. Dietary patterns were assessed by the Alternate Healthy Eating Index 2010 (AHEI-2010), Dietary Approach to Stop Hypertension (DASH), and Alternate Mediterranean Diet (AMED).

Main outcome measures Five repeated measurements of four year changes in body mass index and body weight over follow-up (1986 to 2006).

Results During a 20 year follow-up, genetic association with change in body mass index was significantly attenuated with increasing adherence to the AHEI-2010 in the Nurses’ Health Study (P=0.001 for interaction) and Health Professionals Follow-up Study (P=0.005 for interaction). In the combined cohorts, four year changes in body mass index per 10 risk allele increment were 0.07 (SE 0.02) among participants with decreased AHEI-2010 score and −0.01 (0.02) among those with increased AHEI-2010 score, corresponding to 0.16 (0.05) kg versus −0.02 (0.05) kg weight change every four years (P<0.001 for interaction). Viewed differently, changes in body mass index per 1 SD increment of AHEI-2010 score were −0.12 (0.01), −0.14 (0.01), and −0.18 (0.01) (weight change: −0.35 (0.03), −0.36 (0.04), and −0.50 (0.04) kg) among participants with low, intermediate, and high genetic risk, respectively. Similar interaction was also found for DASH but not for AMED.

Conclusions These data indicate that improving adherence to healthy dietary patterns could attenuate the genetic association with weight gain. Moreover, the beneficial effect of improved diet quality on weight management was particularly pronounced in people at high genetic risk for obesity.


  • Contributors: TW and LQ conceived and designed the study. EBR, JEM, FBH, WCW, and LQ acquired the data. TW did the analyses and drafted the manuscript. All authors contributed to the interpretation of the results and critical revision of the manuscript for important intellectual content and approved the final version of the manuscript. LQ is the guarantor.

  • Funding: The cohorts were supported by grants R01 CA49449, UM1 CA186107, and UM1 CA167552 from the National Institutes of Health. This study was supported by grants from the National Heart, Lung, and Blood Institute (HL071981, HL034594, HL126024, HL35464), the National Institute of Diabetes and Digestive and Kidney Diseases (DK091718, DK100383, DK078616), the National Eye Institute (EY015473), the National Human Genome Research Institute (U01 HG004728), and the National Institute of Health (CA87969, CA49449, CA55075, CA167552). TW is supported by the National Natural Science Foundation of China (81500610). LQ is supported by the American Heart Association Scientist Development Award (0730094N). All investigators are independent from funders.

  • Competing interests: All authors have completed the ICMJE uniform disclosure form at and declare: no support from any organization for the submitted work other than that described above; no financial relationships with any organizations that might have an interest in the submitted work in the previous three years; no other relationships or activities that could appear to have influenced the submitted work.

  • Ethical approval: The study protocol was approved by the institutional review boards of Brigham and Women’s Hospital and Harvard T.H. Chan School of Public Health. The completion of the self administered questionnaire was considered to imply informed consent.

  • Data sharing: Data, the statistical code, questionnaires, and technical processes are available from the corresponding author at

  • Transparency statement: LQ affirms that the manuscript is an honest, accurate, and transparent account of the study being reported; that no important aspects of the study have been omitted; and that any discrepancies from the study as planned (and, if relevant, registered) have been explained.

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