A genome-wide association meta-analysis identifies new childhood obesity loci

Multiple genetic variants have been associated with adult obesity and a few with severe obesity in childhood; however, less progress has been made in establishing genetic influences on common early-onset obesity. We performed a North American, Australian and European collaborative meta-analysis of 14 studies consisting of 5,530 cases (≥95th percentile of body mass index (BMI)) and 8,318 controls (<50th percentile of BMI) of European ancestry. Taking forward the eight newly discovered signals yielding association with P < 5 × 10(-6) in nine independent data sets (2,818 cases and 4,083 controls), we observed two loci that yielded genome-wide significant combined P values near OLFM4 at 13q14 (rs9568856; P = 1.82 × 10(-9); odds ratio (OR) = 1.22) and within HOXB5 at 17q21 (rs9299; P = 3.54 × 10(-9); OR = 1.14). Both loci continued to show association when two extreme childhood obesity cohorts were included (2,214 cases and 2,674 controls). These two loci also yielded directionally consistent associations in a previous meta-analysis of adult BMI(1).

Six new loci associated with body mass index highlight a neuronal influence on body weight regulation

Common variants at only two loci, FTO and MC4R, have been reproducibly associated with body mass index (BMI) in humans. To identify additional loci, we conducted meta-analysis of 15 genome-wide association studies for BMI (n > 32,000) and followed up top signals in 14 additional cohorts (n > 59,000). We strongly confirm FTO and MC4R and identify six additional loci (P < 5 x 10(-8)): TMEM18, KCTD15, GNPDA2, SH2B1, MTCH2 and NEGR1 (where a 45-kb deletion polymorphism is a candidate causal variant). Several of the likely causal genes are highly expressed or known to act in the central nervous system (CNS), emphasizing, as in rare monogenic forms of obesity, the role of the CNS in predisposition to obesity.

The unsung heroes

This paper explores the roles played by local collectors, often little-known or rarely remembered, in the compilation of Britain’s Earlier (Lower and early Middle) Palaeolithic record, with reference to the work of C.E. (Charles) Bean at the Lower Palaeolithic site of Broom, and the activities of George Smith and Llewellyn and Mabel Treacher in the Middle Thames Valley. Their collecting practices, publication records, and archaeological knowledge and insights are reviewed, and their impacts assessed with reference to the activities of other contemporary collectors, and the regional archaeological records of the south-west and the Middle Thames. Their archives demonstrate that while the key sites and artefact assemblages sampled by Bean, Smith and the Treachers would not otherwise have been unknown, their work left important legacies in terms of rich artefact assemblages, site archives (Bean), and the long-term monitoring of key sites and fluvial terraces.

Taylor v Caldwell (1863)

A Landmark Case is one which stands out from other less remarkable cases. Landmark status is generally accorded because the case marks the beginning or the end of a course of legal development. Taylor v Caldwell is regarded as a landmark case because it marks the beginning of a legal development: the introduction of the doctrine of frustration into English contract law. This chapter explores the legal and historical background to the case to ascertain if it is a genuine landmark. A closer scrutiny reveals that while the legal significance of the case is exaggerated, the historical significance of the cases reveals an unknown irony: the case is a suitable landmark to the frustration of human endeavours. While the existence of the Surrey Music Hall was brief, it brought insanity, imprisonment, bankruptcy and death to its creators.