We are involved in this study in conjunction with St Georges Hospital Medical School. The hormone leptin secreted into the bloodstream by fat stores acts in the brain to reduce appetite when reserves are sufficient for the body’s normal needs. Strangely, most overweight people have high circulating leptin but still over-eat, showing they are not responding properly to leptin. The fault could lie in the mechanism by which leptin initiates its inhibitory effect on appetite after binding to specific receptors in the brain. The aim of this study is to find if common variations in the genes that control this pathway are found more often in people towards the heavier end of the normal body weight range and to investigate ways in which the variants might interfere with a normal response to leptin. To be sure of detecting the small contribution to overall weight that we would expect from only four genes, the study will be based on a total of approx. 2800 adult subjects. Any gene variants linked to development of overweight could be used to identify at-risk individuals early in life for advice or treatment.