Sex-differential associations of BMI polygenic scores in youth with the double burden of malnutrition

ObjectiveTo examine associations of BMI-related polygenic scores (PGSs) with BMI-for-age z-score (BMIz), height-for-age z-score (HAZ), and weight; assess sex-specific effects; and test PGS-by-diet interactions in youth experiencing the double burden of malnutrition. MethodsIn this cross-sectional study of Filipino youth aged 6-19 years, we analyzed genome-wide genotype, anthropometric, and dietary data from two 24-hour recalls. Four ancestry-standardized BMI PGSs were evaluated using linear regression adjusted for age, sex, and ancestry principal components, with platform-specific estimates combined by fixed-effects meta-analysis. ResultsAll four PGSs were positively associated with BMIz ({beta} range: 0.119 - 0.320). The strongest association was observed for the multi-ancestry score PGS005202 ({beta} = 0.320; P = 2.39 x 10-9; {Delta}R2 = 4.98%). No PGS was associated with HAZ. PGS005202 and PGS005279 were associated with higher weight independent of HAZ. A significant PGS000716-by-sex interaction was observed for BMIz (q = 0.034), with an association in boys ({beta} = 0.253; P = 0.002) but not in girls ({beta} = -0.007; P = 0.93). No PGS-by-diet interaction remained significant after multiple-testing correction. ConclusionsBMI-related PGSs were associated with adiposity-related traits, but not linear growth, in Filipino youth. Findings support sex-stratified analyses and further evaluation of ancestry-inclusive PGSs in similar pediatric settings.