title: Saturated fat intake modulates the association between an obesity genetic risk score and body mass index in two US populations.
abstract: 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.
authors.forename: Patricia
authors.initials: P
authors.lastname: Casas-Agustench
authors.forename: Donna K
authors.initials: DK
authors.lastname: Arnett
authors.forename: Caren E
authors.initials: CE
authors.lastname: Smith
authors.forename: Chao-Qiang
authors.initials: CQ
authors.lastname: Lai
authors.forename: Laurence D
authors.initials: LD
authors.lastname: Parnell
authors.forename: Ingrid B
authors.initials: IB
authors.lastname: Borecki
authors.forename: Alexis C
authors.initials: AC
authors.lastname: Frazier-Wood
authors.forename: Matthew
authors.initials: M
authors.lastname: Allison
authors.forename: Yii-Der Ida
authors.initials: YD
authors.lastname: Chen
authors.forename: Kent D
authors.initials: KD
authors.lastname: Taylor
authors.forename: Stephen S
authors.initials: SS
authors.lastname: Rich
authors.forename: Jerome I
authors.initials: JI
authors.lastname: Rotter
authors.forename: Yu-Chi
authors.initials: YC
authors.lastname: Lee
authors.forename: José M
authors.initials: JM
authors.lastname: Ordovás
mesh_terms: D000328:Adult; D000368:Aged; D015992:Body Mass Index; D003430:Cross-Sectional Studies; D004032:Diet; D004041:Dietary Fats / Q000008:administration & dosage; D002149:Energy Intake; D005227:Fatty Acids / Q000008:administration & dosage* / Q000009:adverse effects*; D005260:Female; D059647:Gene-Environment Interaction; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D008019:Life Style; D016014:Linear Models; D008297:Male; D008875:Middle Aged; D009043:Motor Activity; D015596:Nutrition Assessment; D009765:Obesity / Q000453:epidemiology* / Q000235:genetics*; D012307:Risk Factors; D014481:United States / Q000453:epidemiology; D044465:White People / Q000235:genetics
chemical_list: D004041:Dietary Fats; D005227:Fatty Acids
keywords: Body mass index; Genetic risk score; Obesity; Saturated fat; Saturated fatty acids