TY - JOUR
T1 - Metabolically favorable adiposity and bone mineral density
T2 - a Mendelian randomization analysis
AU - Bland, Victoria L.
AU - Bea, Jennifer W.
AU - Going, Scott B.
AU - Yaghootkar, Hanieh
AU - Arora, Amit
AU - Ramadan, Ferris
AU - Funk, Janet L.
AU - Chen, Zhao
AU - Klimentidis, Yann C.
N1 - Funding Information:
Hanieh Yaghootkar is funded by Diabetes UK RD Lawrence fellowship (grant: 17/0005594).
Funding Information:
This research was conducted using the UK Biobank Resource under application #52264. The authors thank the participants and organizers of the UK Biobank. Ethical approval for the UK Biobank study was obtained from the National Health Service North West Multicenter Research Ethics Committee. The authors would also like to acknowledge the vital contributions of the GEFOS Consortia, as well as all organizers and participants of individual participating studies.
Publisher Copyright:
© 2022 The Obesity Society.
PY - 2023/1
Y1 - 2023/1
N2 - Objective: This analysis assessed the putative causal association between genetically predicted percent body fat and areal bone mineral density (aBMD) and, more specifically, the association between genetically predicted metabolically “favorable adiposity” (MFA) and aBMD at clinically relevant bone sites. Methods: Mendelian randomization was used to assess the relationship of MFA and percent body fat with whole-body, lumbar spine, femoral neck, and forearm aBMD. Sex-stratified and age-stratified exploratory analyses were conducted. Results: In all MR analyses, genetically predicted MFA was inversely associated with aBMD for the whole body (β = −0.053, p = 0.0002), lumbar spine (β = −0.075; p = 0.0001), femoral neck (β = −0.045; p = 0.008), and forearm (β = −0.115; p = 0.001). This negative relationship was strongest in older individuals and did not differ by sex. The relationship between genetically predicted percent body fat and aBMD was nonsignificant across all Mendelian randomization analyses. Several loci that were associated at a genome-wide significance level (p < 5 × 10−8) in opposite directions with body fat and aBMD measures were also identified. Conclusions: This study did not support the hypothesis that MFA protects against low aBMD. Instead, it showed that MFA may result in lower aBMD. Further research is needed to understand how MFA affects aBMD and other components of bone health such as bone turnover, bone architecture, and osteoporotic fractures.
AB - Objective: This analysis assessed the putative causal association between genetically predicted percent body fat and areal bone mineral density (aBMD) and, more specifically, the association between genetically predicted metabolically “favorable adiposity” (MFA) and aBMD at clinically relevant bone sites. Methods: Mendelian randomization was used to assess the relationship of MFA and percent body fat with whole-body, lumbar spine, femoral neck, and forearm aBMD. Sex-stratified and age-stratified exploratory analyses were conducted. Results: In all MR analyses, genetically predicted MFA was inversely associated with aBMD for the whole body (β = −0.053, p = 0.0002), lumbar spine (β = −0.075; p = 0.0001), femoral neck (β = −0.045; p = 0.008), and forearm (β = −0.115; p = 0.001). This negative relationship was strongest in older individuals and did not differ by sex. The relationship between genetically predicted percent body fat and aBMD was nonsignificant across all Mendelian randomization analyses. Several loci that were associated at a genome-wide significance level (p < 5 × 10−8) in opposite directions with body fat and aBMD measures were also identified. Conclusions: This study did not support the hypothesis that MFA protects against low aBMD. Instead, it showed that MFA may result in lower aBMD. Further research is needed to understand how MFA affects aBMD and other components of bone health such as bone turnover, bone architecture, and osteoporotic fractures.
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U2 - 10.1002/oby.23604
DO - 10.1002/oby.23604
M3 - Article
C2 - 36502291
AN - SCOPUS:85144049599
SN - 1930-7381
VL - 31
SP - 267
EP - 278
JO - Obesity
JF - Obesity
IS - 1
ER -