Causal association between sarcopenia and iron deficiency anemia: A two-sample Mendelian randomization study

Area of Science:

• Genetics
• Epidemiology
• Gerontology

Background:

• Sarcopenia, characterized by age-related muscle loss, and iron deficiency anemia (IDA) are common conditions, particularly in older adults.
• The potential causal relationship between sarcopenia and IDA remains incompletely understood.
• Investigating this link is crucial for developing targeted interventions and improving patient outcomes.

Purpose of the Study:

• To investigate the potential causal links between sarcopenia and iron deficiency anemia (IDA) using a two-sample Mendelian randomization (MR) approach.
• To explore the directionality of the relationship, examining if sarcopenia influences IDA risk and vice versa.
• To identify genetic associations that can inform future research and clinical strategies.

Main Methods:

• A two-sample Mendelian randomization (MR) study was conducted using genome-wide association study (GWAS) data.
• Instrumental variables for physical function traits were selected based on stringent statistical criteria (P < 5 × 10⁻⁸, r² < 0.001, MAF > 0.01, F > 10).
• Inverse-variance weighted (IVW) method was employed, with MR-Egger, weighted median, and weighted mode used for robustness checks and sensitivity analyses.

Main Results:

• Genetically predicted faster walking pace was associated with reduced risk of IDA (OR = 0.534, P < .001) and IDA secondary to chronic blood loss (OR = 0.375, P = .006).
• Genetically predicted higher grip strength was associated with reduced risk of IDA secondary to chronic blood loss (OR = 0.735, P = .04).
• Reverse MR analyses indicated that IDA was associated with slower walking pace (OR = 0.973, P = .01) and IDA secondary to chronic blood loss with reduced grip strength (OR = 0.735, P = .04), suggesting bidirectionality.

Conclusions:

• Lower muscle function, including grip strength and walking pace, is causally associated with an increased risk of iron deficiency anemia.
• Iron deficiency anemia may causally contribute to reduced muscle strength and slower walking pace, indicating a bidirectional relationship.
• Further research is warranted to elucidate the underlying mechanisms and develop effective preventive and therapeutic strategies for both conditions.