Research

Mixed

The ACTN3 missense variant rs2229456 (p.Glu635Ala) is associated with higher odds of engaging in moderate-to-vigorous physical activity (MVPA) and lower leisure screen time (LST), potentially by increasing muscle flexibility and reducing susceptibility to exercise-induced muscle damage.

This finding highlights a specific genetic variant (ACTN3 p.Glu635Ala) that may make some individuals more prone to physical activity and less prone to muscle damage. However, this is just one piece of the puzzle; lifestyle choices remain the primary driver of health outcomes.

ModerateSupportsMEDIUM confidence
a missense variant in ACTN3 makes the alpha-actinin-3 filaments more flexible, resulting in lower maximal force in isolated type IIA muscle fibers, and possibly protection from exercise-induced muscle damage.
Zhe Wang et al. · Nature Genetics · 2022

Why this rating

Strong genetic association data combined with small-scale mechanistic studies (MD simulations and isolated fiber experiments).

Source

Genome-wide association analyses of physical activity and sedentary behavior provide insights into underlying mechanisms and roles in disease prevention

Zhe Wang et al. · Nature Genetics · 2022

DOI 10.1038/s41588-022-01165-1

Meta-analysis · 51 studiesCited 235×
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DOI resolved against Crossref · corpus check 2026-06-10

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