Meta-analysis links BMI polygenic scores to BMI in Filipino youth with double burden of malnutrition
Photo by National Cancer Institute / Unsplash
Key Takeaway
Interpret BMI polygenic score associations cautiously in Filipino youth; cross-sectional design precludes causality.
This meta-analysis pooled cross-sectional data to evaluate the association between BMI-related polygenic scores (PGSs) and anthropometric outcomes in Filipino youth aged 6-19 years who experience a double burden of malnutrition. The analysis included four PGSs and assessed their relationship with BMI-for-age z-score (BMIz), height-for-age z-score (HAZ), and weight.
All four PGSs were positively associated with BMIz, with beta values ranging from 0.119 to 0.320. The strongest association was observed for PGS005202 (P=2.39x10-9). No PGS was associated with HAZ. Two PGSs (PGS005202 and PGS005279) were associated with higher weight independent of HAZ. A sex-stratified analysis revealed a significant PGS000716-by-sex interaction: the association with BMIz was present in boys (beta=0.253, P=0.002) but not in girls (beta=-0.007, P=0.93; interaction q=0.034).
The authors note that these are associations, not causal relationships, and the cross-sectional design limits causal inference. Results are specific to Filipino youth and may not generalize to other populations. Limitations such as sample size and setting were not reported. The findings highlight potential genetic contributions to the double burden of malnutrition in this population, but clinical application remains uncertain without further longitudinal or interventional studies.
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View Original Abstract ↓
Objective: To examine the 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. Methods: In this cross-sectional study of Filipino youth aged 6-19 years, we analyzed genome-wide genotype, anthropometric, and dietary data from two 24-hour food 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. Results: All 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=2.39x10-9; {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. Conclusion: BMI-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.
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