Saturated Fat Intake Modulates the Association between an Obesity Genetic Risk Score and Body Mass Index in Two US Populations

Patricia Casas-Agustench, Donna K. Arnett, Caren E. Smith, Chao Qiang Lai, Laurence D. Parnell, Ingrid B. Borecki, Alexis C. Frazier-Wood, Matthew Allison, Yii Der Ida Chen, Kent D. Taylor, Stephen S. Rich, Jerome I. Rotter, Yu Chi Lee, José M. Ordovás

Research output: Contribution to journalArticlepeer-review

51 Scopus citations


Combining multiple genetic variants related to obesity into a genetic risk score (GRS) might improve identification of individuals at risk of developing obesity. Moreover, characterizing gene-diet interactions is a research challenge to establish dietary recommendations to individuals with higher predisposition to obesity. Our objective was to analyze the association between an obesity GRS and body mass index (BMI) in the Genetics of Lipid Lowering Drugs and Diet Network (GOLDN) population, focusing on gene-diet interactions with total fat and saturated fatty acid (SFA) intake, and to replicate findings in the Multi-Ethnic Study of Atherosclerosis (MESA) population. Cross-sectional analyses included 783 white US participants from GOLDN and 2,035 from MESA. Dietary intakes were estimated with validated food frequency questionnaires. Height and weight were measured. A weighted GRS was calculated on the basis of 63 obesity-associated variants. Multiple linear regression models adjusted by potential confounders were used to examine gene-diet interactions between dietary intake (total fat and SFA) and the obesity GRS in determining BMI. Significant interactions were found between total fat intake and the obesity GRS using these variables as continuous for BMI (P for interaction=0.010, 0.046, and 0.002 in GOLDN, MESA, and meta-analysis, respectively). These association terms were stronger when assessing interactions between SFA intake and GRS for BMI (P for interaction=0.005, 0.018, and <0.001 in GOLDN, MESA, and meta-analysis, respectively). SFA intake interacts with an obesity GRS in modulating BMI in two US populations. Although determining the causal direction requires further investigation, these findings suggest that potential dietary recommendations to reduce BMI effectively in populations with high obesity GRS would be to reduce total fat intake mainly by limiting SFAs.

Original languageEnglish
Pages (from-to)1954-1966
Number of pages13
JournalJournal of the Academy of Nutrition and Dietetics
Issue number12
StatePublished - Dec 1 2014

Bibliographical note

Funding Information:
FUNDING/SUPPORT Supported by the National Institutes of Health (grant nos. 1R21AR055228-01A1 , HL54776 , 5R21HL114238-02 , and U01 HL72524 ), the National Institute of Diabetes and Digestive and Kidney Diseases (grant no. DK075030 ), and the US Department of Agriculture Research Service (grant nos. 53-K06-5-10 , 58–1950-9-001 , and K08 HL112845-01 ); support for MESA is provided by contracts N01-HC-95159 , N01-HC-95160, N01-HC-95161 , N01-HC-95162 , N01-HC-95163 , N01-HC-95164 , N01-HC-95165, N01-HC-95166 , N01-HC-95167 , N01-HC-95168 , N01-HC-95169 , UL1-TR-001079 , and UL1-TR-000040 ; SHARE genotyping was provided by National Heart, Lung, Blood Institute contract NO2-HL-64278 , the provision of genotyping data was supported in part by the National Center for Advancing Translational Sciences, Clinical and Translational Science Institute grant UL1TR000124 , and the National Institute of Diabetes and Digestive and Kidney Disease Diabetes Research Center grant DK063491 to the Southern California Diabetes Endocrinology Research Center. Mention of trade names or commercial products in this publication is solely for the purpose of providing specific information and does not imply recommendation or endorsement by the US Department of Agriculture. The US Department of Agriculture is an equal opportunity provider and employer. This research project received funding from the European Union Seventh Framework Programme (FP7/2007-2013) under grant agreement no. PIOF-GA-2010-272581 .

Publisher Copyright:
© 2014 Academy of Nutrition and Dietetics.


  • Body mass index
  • Genetic risk score
  • Obesity
  • Saturated fat
  • Saturated fatty acids

ASJC Scopus subject areas

  • Food Science
  • Nutrition and Dietetics


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