A. J. Payne

Warming and Melting Mass loss from the ice sheets of Greenland and Antarctica account for a large fraction of global sea-level rise. Part of this loss is because of the effects of warmer air temperatures, and another because of the rising ocean temperatures to which they are being exposed. Joughin et al. (p. 1172 ) review how ocean-ice interactions are impacting ice sheets and discuss the possible ways that exposure of floating ice shelves and grounded ice margins are subject to the influences of warming ocean currents. Estimates of the mass balance of the ice sheets of Greenland and Antarctica have differed greatly—in some cases, not even agreeing about whether there is a net loss or a net gain—making it more difficult to project accurately future sea-level change. Shepherd et al. (p. 1183 ) combined data sets produced by satellite altimetry, interferometry, and gravimetry to construct a more robust ice-sheet mass balance for the period between 1992 and 2011. All major regions of the two ice sheets appear to be losing mass, except for East Antarctica. All told, mass loss from the polar ice sheets is contributing about 0.6 millimeters per year (roughly 20% of the total) to the current rate of global sea-level rise.

Scalable, integrative methods to understand mechanisms that link genetic variants with phenotypes are needed. Here we derive a mathematical expression to compute PrediXcan (a gene mapping approach) results using summary data (S-PrediXcan) and show its accuracy and general robustness to misspecified reference sets. We apply this framework to 44 GTEx tissues and 100+ phenotypes from GWAS and meta-analysis studies, creating a growing public catalog of associations that seeks to capture the effects of gene expression variation on human phenotypes. Replication in an independent cohort is shown. Most of the associations are tissue specific, suggesting context specificity of the trait etiology. Colocalized significant associations in unexpected tissues underscore the need for an agnostic scanning of multiple contexts to improve our ability to detect causal regulatory mechanisms. Monogenic disease genes are enriched among significant associations for related traits, suggesting that smaller alterations of these genes may cause a spectrum of milder phenotypes.

Increased concentrations of atmospheric greenhouse gases have led to a global mean surface temperature 1.0°C higher than during the pre-industrial period. We expand on the recent IPCC Special Report on global warming of 1.5°C and review the additional risks associated with higher levels of warming, each having major implications for multiple geographies, climates, and ecosystems. Limiting warming to 1.5°C rather than 2.0°C would be required to maintain substantial proportions of ecosystems and would have clear benefits for human health and economies. These conclusions are relevant for people everywhere, particularly in low- and middle-income countries, where the escalation of climate-related risks may prevent the achievement of the United Nations Sustainable Development Goals.

Many complex human phenotypes exhibit sex-differentiated characteristics. However, the molecular mechanisms underlying these differences remain largely unknown. We generated a catalog of sex differences in gene expression and in the genetic regulation of gene expression across 44 human tissue sources surveyed by the Genotype-Tissue Expression project (GTEx, v8 release). We demonstrate that sex influences gene expression levels and cellular composition of tissue samples across the human body. A total of 37% of all genes exhibit sex-biased expression in at least one tissue. We identify cis expression quantitative trait loci (eQTLs) with sex-differentiated effects and characterize their cellular origin. By integrating sex-biased eQTLs with genome-wide association study data, we identify 58 gene-trait associations that are driven by genetic regulation of gene expression in a single sex. These findings provide an extensive characterization of sex differences in the human transcriptome and its genetic regulation.