Our replication of the obesity association of deletions including SH2B1 and the finding of limited evidence to support 2 further associations, together with recent successes in other disorders including attention deficit hyperactivity disorder [43], demonstrate that analysis of carefully-selected cohorts has the potential to reveal novel, rare, causal GSVs. The gene discussed is SH2B1; the disease is obesity due to melanocortin 4 receptor deficiency.