Large quantitative effect of melanocortin-4 receptor gene mutations on body mass index

The mean effect of each single mutation on the phenotype can only be estimated reliably from a large enough population or family based sample. Because most of our detected mutations segregated in only one single family with a limited number of mutation carriers and WT individuals, respectively, this expected random variation also contributes to the interfamilial differences in observed effects of different mutations. [...]our approach of recruiting relatives of known mutation carriers is a solid strategy to estimate the quantitative effect of genetic variants in a sample enriched for mutation carriers.