Current smoking (14.1%), sleep (12.3%: 6.2% from short sleep duration and 6.1% from sleep disturbance), adiposity (9.8%: 4.9% from obesity and central obesity, respectively), HbA1c (10.7%) and cystatin C (5.5%) were identified as the main mediators. The gene discussed is CST3; the disease is obesity due to melanocortin 4 receptor deficiency.