Ruth Loos and colleagues report results of a large genome-wide association study for body mass index. They identify 18 new loci associated with this trait, some of which map near key hypothalamic regulators of energy balance. Obesity is globally prevalent and highly heritable, but its underlying genetic factors remain largely elusive. To identify genetic loci for obesity susceptibility, we examined associations between body mass index and ∼2.8 million SNPs in up to 123,865 individuals with targeted follow up of 42 SNPs in up to 125,931 additional individuals. We confirmed 14 known obesity susceptibility loci and identified 18 new loci associated with body mass index (P < 5 × 10−8), one of which includes a copy number variant near GPRC5B. Some loci (at MC4R, POMC, SH2B1 and BDNF) map near key hypothalamic regulators of energy balance, and one of these loci is near GIPR, an incretin receptor. Furthermore, genes in other newly associated loci may provide new insights into human body weight regulation.

Although in the past century mortality in West Germany decreased similarly as in other Western nations, these changes were less pronounced in East Germany.^1,2 After German reunification in 1990, there was a lack of scientifically valid data from East Germany to explain the regional differences in life expectancy and, consequently, a need for population-based research in northeast Germany.

The clinical symptoms of restless legs syndrome (RLS) were first described by the English physician Sir Thomas Willis¹ in a chapter entitled "Instructions for Curing the Watching Evil" of his book The London Practice of Physick in 1685. His original description related the experience of patients: "The diseased are no more able to sleep, than if they were in a place of greatest torture."^1(p404) In later centuries, the condition was described with varying terms and generally was regarded as a form of hysteria or neurasthenia.² The Swedish neurologist Karl Ekbohm gave the comprehensive description a disease entity, "irritable legs," in 1944.³ However, it took another 50 years until standard criteria for the definition and diagnosis of RLS were published by the International Restless Legs Syndrome Study Group in 1995.⁴ These criteria include the desire to move the limbs usually associated with paresthesias or dysesthesias of the legs, a motor restlessness, a worsening or exclusive presence of symptoms at rest (lying or sitting) with at least partial and temporary relief by activity, and a worsening of the symptoms in the evening or during the night. Between 50% and 92% of patients with idiopathic RLS report a positive family history.⁵ Based on the analysis of large families, autosomal dominant inheritance is suggested.^6,7 Symptomatic forms of RLS can occur during pregnancy, in uremic patients, and in those with diabetes mellitus or anemia.⁸