Is Coffee Intake Associated with Obesity-Related Traits? . A Mendelian Randomization/Pleiotropy Approach Using United Kingdom Biobank (UKBB) Database

CARLOS JOSE PIROLA; SILVIA SOOKOIAN

Seattle

Congreso; American Society Nutrition Annual Meeting; 2020

American Society Nutrition

Objectives: Epidemiological studies suggest that coffee intake (CI) is protective against body weight gain. We explored whether genetic determinants of CI are associated with obesity-related phenotypic traits, primarily body mass Index (BMI).Methods: We leveraged information from ~354000 individuals in the UKBB database (https://genetics.opentargets.org/) searching for genetic variants associated with CI (cutoff p< 0.5E-8). We further explored the association of these variants with BMI and other obesity-related traits (body fat percentage-BFP, obesity or waist circumference-WC) using summarized data from Neale´s lab (http://www.nealelab.is/uk-biobank/).ResultsTwenty seven variants were significantly associated with CI, including rs2472297-CYP1A1/2 (p=3.4E-116, beta(b)=0.047) and rs4410790-AHR- (p=3.2E-95, b=0.039), which were previously reported to be associated with CI. Seventeen variants showed significant associations with BMI in the same direction (i.e. rs2472297- CYP1A1/2, p=1.2E-6, b=0.06; rs4410790-AHR, p=1.7E-4 ,b=0.04; rs589500-SEC16B, p=2.5E-59, b=0.22; rs1260326-GCKR, p=8.0E-6,b=0.05; rs3814424-MEF2C,p=6.3E-20,b=0.14; rs1189470082-AL355997.1, p=4.3E-8,b=0.07; rs9398171-LINC00222/FOXO3, p=6.1E-10, b=0.08; rs370535199-KBTBD2, p=9.2E-5, b=0.045; rs1057868-POR,p=9.9E-6,b=0.055; rs56094641-FTO, p=2.1E-219, b=0.26). The remaining 9 variants showed no associations with any obesity-related traits. One variant (rs57918684-MED13) showed a marginal and opposite direction effect. Beta coefficients for CI and BMI were significantly correlated (Spearman R: 0.69, p< 0.0001), which is compatible with a significant genetic correlation between both traits (rg= 0.24±0.02, p=4.06E-23). The positive association between CI and BMI is biologically supported by genetic correlations between CI and food intake (rg= 0.26±0.07, p=1.0E-4), BFP (rg= 0.16±0.02, p= 2.54E-13) and WC (rg= 0.23±0.02, p= 2.0E-22).Conclusions:Variants associated with CI present direct pleiotropic effects on obesity-related traits such as BMI, BFP, and WC. If these are not causal relations, then from a Mendelian Randomization point of view, CI may have an undesirable effect.