BACKGROUND: Genetic predisposition to adiposity may interact with dietary protein in relation to changes of anthropometry. OBJECTIVE: To investigate the interaction between genetic predisposition to higher body mass index (BMI), waist circumference (WC) or waist-hip ratio adjusted for BMI (WHRBMI) and dietary protein in relation to subsequent change in body weight (ΔBW) or change in WC (ΔWC). DESIGN: Three different Danish cohorts were used. In total 7,054 individuals constituted the study population with information on diet, 50 single-nucleotide polymorphisms (SNPs) associated with BMI, WC or WHRBMI, as well as potential confounders. Mean follow-up time was ∼5 years. Four genetic predisposition-scores were based on the SNPs; a complete-score including all selected adiposity- associated SNPs, and three scores including BMI, WC or WHRBMI associated polymorphisms, respectively. The association between protein intake and ΔBW or ΔWC were examined and interactions between SNP-score and protein were investigated. Analyses were based on linear regressions using macronutrient substitution models and meta-analyses. RESULTS: When protein replaced carbohydrate, meta-analyses showed no associations with ΔBW (41.0 gram/y/5 energy% protein, [95% CI: -32.3; 114.3]) or ΔWC (<-0.1 mm/y/5 energy % protein, [-1.1; 1.1]). Similarly, there were no interactions for any SNP-scores and protein for either ΔBW (complete SNP-score: 1.8 gram/y/5 energy% protein/risk allele, [-7.0; 10.6]) or ΔWC (complete SNP-score: <0.1 mm/y/5 energy% protein/risk allele, [-0.1; 0.1]). Similar results were seen when protein replaced fat. CONCLUSION: This study indicates that the genetic predisposition to general and abdominal adiposity, assessed by gene-scores, does not seem to modulate the influence of dietary protein on ΔBW or ΔWC.