One is the result of synergism between AGT TT, PAI-1 4G/4G, and other unidentified genetic factors associated with FH and/or aging; the other pathway results from synergism between the NOS3 GA+AA genotype and other unidentified genetic factors associated with FH and/or obesity. The gene discussed is SERPINE1; the disease is obesity due to melanocortin 4 receptor deficiency.