Genetic variants and physical activity interact to affect bone density in Hispanic children

Ruixue Hou,Sandra Laston,Nancy F Butte,Roman J Shypailo,Shelley A Cole,Venkata Saroja Voruganti,Nitesh R Mehta,Karin Haack,Anthony G Comuzzie,Kari E North,Mariaelisa Graff,Margaret L Gourlay,Yujie Wang

doi:10.1186/s12887-021-02537-y

Abstract

BackgroundOur aim was to investigate if moderate to vigorous physical activity (MVPA), calcium intake interacts with bone mineral density (BMD)-related single nucleotide polymorphisms (SNPs) to influence BMD in 750 Hispanic children (4-19y) of the cross-sectional Viva La Familia Study.MethodsPhysical activity and dietary intake were measured by accelerometers and multiple-pass 24 h dietary recalls, respectively. Total body and lumbar spine BMD were measured by dual energy X-ray absorptiometry. A polygenic risk score (PRS) was computed based on SNPs identified in published literature. Regression analysis was conducted with PRSs, MVPA and calcium intake with total body and lumbar spine BMD.ResultsWe found evidence of statistically significant interaction effects between the PRS and MVPA on total body BMD and lumbar spine BMD (p < 0.05). Higher PRS was associated with a lower total body BMD (β = − 0.040 ± 0.009, p = 1.1 × 10− 5) and lumbar spine BMD (β = − 0.042 ± 0.013, p = 0.0016) in low MVPA group, as compared to high MVPA group (β = − 0.015 ± 0.006, p = 0.02; β = 0.008 ± 0.01, p = 0.4, respectively).DiscussionThe study indicated that calcium intake does not modify the relationship between genetic variants and BMD, while it implied physical activity interacts with genetic variants to affect BMD in Hispanic children. Due to limited sample size of our study, future research on gene by environment interaction on bone health and functional studies to provide biological insights are needed.ConclusionsBone health in Hispanic children with high genetic risk for low BMD is benefitted more by MVPA than children with low genetic risk. Our results may be useful to predict disease risk and tailor dietary and physical activity advice delivery to people, especially children.

Highlights

Osteoporosis and low bone mass are major public health threats with great economic burden in the U.S Maximizing peak bone mass in early life is an important strategy to prevent osteoporosis in later life
In one study of European children, significant interaction was found between physical activity and a polygenic risk score (PRS) computed from selected Single nucleotide polymorphisms (SNP) identified from published genome-wide association studies (GWAS) [8]
1 Polygenic Risk Score includes SNPs that are statistically significant or nominally significant associated with BMD in Viva La Familia Study 2 BMD bone mineral density, DGKZ Diacylglycerol Kinase Zeta, PRS Polygenic Risk Score, KCNMA1 Potassium Calcium-Activated Channel Subfamily M Alpha 1, LEKR1 Leucine, Glutamate and Lysine Rick 1, MAP 4K3 Mitogen-Activated Protein Kinase Kinase Kinase Kinase 3, RPS6KA5 Ribosomal Protein S6 Kinase A5, SEM1 26S Proteasome Complex Subunit, Solute Carrier Family 8 Member A1 (SLC8A1) Solute Carrier Family 8, SUPT3H SPT3 Homolog, SAGA and STAGA Complex Component larger bones [24], we considered adding height into the current model for sensitivity analysis

Summary

Introduction

Osteoporosis and low bone mass are major public health threats with great economic burden in the U.S Maximizing peak bone mass in early life is an important strategy to prevent osteoporosis in later life. In one study of European children, significant interaction was found between physical activity and a PRS computed from selected SNPs identified from published genome-wide association studies (GWAS) [8]. None of these studies have been conducted in a Hispanic population nor investigated genome-wide SNPs to identify significant genotypes that would interact with physical activity or calcium intake to affect BMD. Our aim was to investigate if moderate to vigorous physical activity (MVPA), calcium intake interacts with bone mineral density (BMD)-related single nucleotide polymorphisms (SNPs) to influence BMD in 750 Hispanic children (4-19y) of the cross-sectional Viva La Familia Study

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