Individuals carrying the APOA5 56 G/G genotype with a high saturated fatty acid consumption ≥12 g/d (OR = 2.7, 95 % CI 1.3–5.6; P = 0.006) and/or total fat ≥83 g/d (OR = 2.4, 95 % CI 1.2–4.9; P = 0.018) were associated with an increased risk of obesity. Here, APOA5 is linked to obesity due to melanocortin 4 receptor deficiency.