At follow‐up, participants with the greatest increase in irisin (Tertile 3) had greater increases in WC (p = 0.003), a higher prevalence of obesity (p = 0.016) and abdominal obesity (p = 0.014), higher body fat mass (p = 0.021) and faster gait speed (p = 0.014) compared to those with the least increased or decreased irisin (Tertile 1). The gene discussed is FNDC5; the disease is obesity due to melanocortin 4 receptor deficiency.