Waist-hip ratio (WHR) is a measure of body fat distribution and a predictor of metabolic consequences independent of overall adiposity. WHR is heritable, but few genetic variants influencing this trait have been identified. We conducted a meta-analysis of 32 genome-wide association studies for WHR adjusted for body-mass-index (up to 77,167 participants), following up 16 loci in an additional 29 studies (up to 113,636 subjects). We identified 13 novel loci in or near RSPO3, VEGFA, TBX15-WARS2, NFE2L3, GRB14, DNM3-PIGC, ITPR2-SSPN, LY86, HOXC13, ADAMTS9, ZNRF3-KREMEN1, NISCH-STAB1, and CPEB4 (P 1.9 × 10−9 to 1.8 × 10−40), and the known signal at LYPLAL1. Seven of these loci exhibited marked sexual dimorphism, all with a stronger effect on WHR in women than men (P for sex-difference 1.9 × 10−3 to 1.2 × 10−13). These findings provide evidence for multiple loci that modulate body fat distribution, independent of overall adiposity, and reveal powerful gene-by-sex interactions.

Chronic kidney disease (CKD), impairment of kidney function, is a serious public health problem, and the assessment of genetic factors influencing kidney function has substantial clinical relevance. Here, we report a meta-analysis of genome-wide association studies for kidney function–related traits, including 71,149 east Asian individuals from 18 studies in 11 population-, hospital- or family-based cohorts, conducted as part of the Asian Genetic Epidemiology Network (AGEN). Our meta-analysis identified 17 loci newly associated with kidney function–related traits, including the concentrations of blood urea nitrogen, uric acid and serum creatinine and estimated glomerular filtration rate based on serum creatinine levels (eGFRcrea) (P < 5.0 × 10−8). We further examined these loci with in silico replication in individuals of European ancestry from the KidneyGen, CKDGen and GUGC consortia, including a combined total of ~110,347 individuals. We identify pleiotropic associations among these loci with kidney function–related traits and risk of CKD. These findings provide new insights into the genetics of kidney function.

No abstract

Satellite imagery and data from ground surveys are used to reconstruct the integrated pattern of the principal longitudinal and transverse features produced on a continent-wide scale by the last ice sheets in Europe and North America. From modern analogues, it is argued that most longitudinal features reflect flow in the outer zone of the ice sheet, and that most major transverse features reflect relatively stable ice-sheet margins. These principles are tested and, using them alone, detailed patterns for the decay of the last ice sheets in North America, Europe and the British Isles are produced, and periods during which they attained near steady-states identified. These patterns can be calibrated by dated sequences to yield deglaciation isochrons. Application of glaciological models to these geological reconstructions generates detailed prediction of net ablation for the period of ice-sheet decay and, by using evidence of last glaciation stratigraphy, models of the dynamic behaviour of the ice sheets throughout the last glacial period are constructed. These enable volumetric changes, oceanic isotopic changes and erratic dispersal pathways to be reconstructed. Erratic dispersal patterns give a good indication of the long-term distribution of centres of ice sheet mass. Discrepancies between predicted and empirical oceanic isotopic records indicate ways in which the conventional continental timescale of glacial change must be altered to fit the better-dated deep ocean record. In addition discrepancies between predicted and empirical erratic dispersal patterns suggest that conventional views of ice-sheet behaviour based on high latitude models may be inappropriate to the dynamically more active mid-latitude ice sheets based in large part on deformable sediment beds.

Variants in TNS1, GSTCD, and HTR4 are associated with COPD. Our highest risk score category was associated with a 1.6-fold higher COPD risk than the population average score.