Increased body mass index (BMI) and late-life mobility dysfunction; overlap of genetic effects in brain regions
Authors' conclusion
We report a causal effect of obesity on mobility dysfunction. Our findings highlight potential neuronal dysfunctions in regulating predispositions on the causal pathway from obesity to mobility dysfunction.
Study context
- Population
- Chinese adults living in Singapore, BMI measured at average 53 years, TUG test 20 years later
- Participants
- 8,342 adults
- Exposure
- Genetically determined midlife BMI and late-life functional mobility
- Outcome
- Performance of the Timed Up-and-Go test (TUG) in late life
- Follow-up
- 20 years later
Methodological detailspopulation-based longitudinal cohort, mediation analysis
- Population-based longitudinal cohort
- Mediation analysis
Main finding
As reported in the abstract
Causal effect of BMI on late-life TUG scores
Genetically determined BMI effects on late-life TUG scores mediated through midlife BMI (Pindirect-effect = 9.24 × 10-21)
75.83%
Causal effect between BMI and functional mobility in late life, Mendelian randomization (βIVW; PIVW = 0.001)
0.180
Observational data: associations, not effects.
Further findings
Secondary gene enrichment
- Down-regulation of genes at BMI risk loci correlated with poorer functional mobility in substantia nigra and amygdala vs all other tissues
- These genes exhibit differential expression patterns during human brain development
Original publication
Increased BMI and late-life mobility dysfunction; overlap of genetic effects in brain regions. Int J Obes (Lond). Published 14 February 2023. doi:10.
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