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

PIROLA, CARLOS; SOOKOIAN, SILVIA

Current Developments in Nutrition

Rockville

Año: 2020 vol. 4 p. 1670 - 1670

ObjectivesEpidemiological 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).MethodsWe leveraged information from ∼354,000 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 trait. One variant (rs57918684-MED13) showed a marginal and opposite 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).ConclusionsVariants 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 has an undesirable effect.