Major or unipolar depression (UPD) is a major public health problem and cause economic negative consequences in industrialized countries (Hu,2006). Genetic studies offer an important route to understanding its causes. The inheritance of UPD is complex (Levinson,2005) and involves and inter-play of genetic and environmental factors (Farmer & McGuffin,2003;Cervilla et al,2007). There has been a small number of linkage scans. McGuffin and colleagues (2005) reported a genome-wide linkage scan in the first wave of the GlaxoSmith-Kline DeNt Study of 438 affected sib pairs with recurrent UPD. The aim of the proposed work is to investigate genetic overlap between Body Mass Index (BMI), diabetes type 2 ‘metabolic syndrome’ and recurrent UPD. Some recent studies support the hypothesis that there may be shared aetiological factors between recurrent UPD, obesity and physical disorders (Farmer et al,2008;Patten et al,2005). In the course of an ongoing genome-wide association (GWA) study of recurrent UPD, McGuffin and colleagues have collected a wealth of detailed data on chronic co-morbid physical diseases such as obesity, diabetes, heart disease and migraine on both depressive cases and controls. The availability of such information will enable the hypothesis of a genetic overlap between depression and elevated BMI to be explored comprehensively. Therefore we will 1) explore whether polymorphisms in known ‘obesity genes’ FTO and MC4R differ in frequency between depression cases and controls, 2) explore the entire dataset for novel genes associated with BMI, 3) search for SNP associations with the combined phenotype of high BMI/depression, 4) follow up the top 10 ‘hits’ with re-genotyping and/or deep sequencing. The study capitalises on several large case collections with closely comparable data and will use the most cost effective method of examining a large number of SNPs and CNVs at a time when similar studies on other common disorders are yielding exciting novel results