Body shape from birth to adulthood is associated with skeletal development: A Mendelian randomization study

Area of Science:

• Genetics
• Human Physiology
• Developmental Biology

Background:

• Observational studies suggest a link between childhood obesity and adult bone health, but findings are inconsistent.
• Previous research indicates a potential association between body shape during development and skeletal outcomes.
• The causal relationship between body shape and skeletal development requires further investigation.

Purpose of the Study:

• To investigate the potential causal association between body shape from birth to adulthood and skeletal development.
• To explore the influence of various body composition metrics on bone phenotypes.
• To clarify the role of childhood body shape in bone maturation and growth patterns.

Main Methods:

• Two-sample Mendelian randomization (MR) was employed to assess causal relationships.
• Genetic instruments for exposures like BMI, lean mass, fat mass, and circumferences were identified from large-scale genome-wide association studies.
• Inverse-variance weighted analysis served as the primary method, with complementary MR analyses for robustness.

Main Results:

• Childhood and adulthood BMI causally influenced humerus length.
• Childhood and adolescent BMI were associated with tibiofemoral angle.
• Appendicular lean mass, whole body fat mass, waist, and hip circumference were associated with tibia length.
• No causal associations were found between placental weight, birth weight, and bone length/width.

Conclusions:

• Childhood body shape plays a significant role in bone development.
• MR analysis reveals causal links between body composition metrics and skeletal site growth.
• Findings provide insights into factors influencing bone maturation and skeletal development patterns.