Dietary fat and total energy intake modifies the association of genetic profile risk score on obesity: evidence from 48 170 UK Biobank participants

Background:Obesity is a multifactorial condition influenced by both genetics and lifestyle. The aim of this study was to investigate whether the association between a validated genetic profile risk score for obesity (GPRS-obesity) and body mass index (BMI) or waist circumference (WC) was modified by macronutrient intake in a large general population study.Methods:This study included cross-sectional data from 48 170 white European adults, aged 37–73 years, participating in the UK Biobank. Interactions between GPRS-obesity and macronutrient intake (including total energy, protein, fat, carbohydrate and dietary fibre intake) and its effects on BMI and WC were investigated.Results:The 93-single-nucleotide polymorphism (SNP) GPRS was associated with a higher BMI (β: 0.57 kg m−2 per s.d. increase in GPRS (95% confidence interval: 0.53–0.60); P=1.9 × 10−183) independent of major confounding factors. There was a significant interaction between GPRS and total fat intake (P(interaction)=0.007). Among high-fat-intake individuals, BMI was higher by 0.60 (0.52, 0.67) kg m−2 per s.d. increase in GPRS-obesity; the change in BMI with GPRS was lower among low-fat-intake individuals (β: 0.50 (0.44, 0.57) kg m−2). Significant interactions with similar patterns were observed for saturated fat intake (high β: 0.66 (0.59, 0.73) versus low β: 0.49 (0.42, 0.55) kg m−2, P(interaction)=2 × 10−4) and for total energy intake (high β: 0.58 (0.51, 0.64) versus low β: 0.49 (0.42, 0.56) kg m−2, P(interaction)=0.019), but not for protein intake, carbohydrate intake and fibre intake (P(interaction) >0.05). The findings were broadly similar using WC as the outcome.Conclusions:These data suggest that the benefits of reducing the intake of fats and total energy intake may be more important in individuals with high genetic risk for obesity.