Another interesting implication is how quantitative genetics relates to disease phenotypes. How distinct alleles, including modest-effect alleles and major-effect alleles, may interact to shape disease presentation is not well studied. For obesity, although FTO represents consistently the strongest gene in many association studies, it has never been implicated from studies of monogenic forms of obesity. Similarly, although MC4R has been implicated in monogenic forms of obesity, analysis of common variants have been highly inconsistent until large-scale GWASs are conducted (4). Therefore, it is likely that rare alleles work together with common alleles to shape the onset of obesity in human populations and that some genes with rare causal alleles may never show up from studies on common variants.
