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The mechanisms controlling Th2-mediated inflammation are not well defined. Here the authors show that the E3 ubiquitin ligase Grail is involved in a negative feedback loop with Th2-specific transcription factors and regulates Th2-mediated allergic asthma responses.

Grail is an E3 ubiquitin ligase that inhibits T-cell receptor signalling in CD4⁺ T cells. Here the authors show Grail also limits IL-21 receptor expression and function in CD8⁺ T cells, is overactive in these cells in patients with lymphoma, and promotes tumour development in a lymphoma transplant mouse model.

Data from the NASA GRAIL spacecraft recover the lunar gravity field suggesting preservation of a predominantly thermal anomaly in the nearside mantle, which could influence the spatial distribution of deep moonquakes.

Soumya Raychaudhuri and colleagues demonstrate the utility of GRAIL, a software program used to prioritize results from genome-wide association studies for further replication, applied here to rheumatoid arthritis. The authors seek replication of their predictions in additional independent cohorts and report three new genetic loci associated with RA susceptibility.

Ancient lunar basins that formed within about 100 million years after the lunar magma ocean solidified have fully relaxed, owing to the high temperature of the lower crust, and thus escaped detection. This finding explains the discrepancy between the number of basins detected on the Moon (~40) and the number predicted (~300) by an accretion scenario of planet formation.

Jose Florez, Claudia Langenberg, Erik Ingelsson, Inga Prokopenko, Inês Barroso and colleagues perform large-scale association analyses using the Metabochip to gain further insights into the genetic architecture of glucose regulation. They identify 38 new loci influencing 1 or more glycemic traits and show that many of these loci also modify risk of type 2 diabetes.

Timothy Frayling, Joel Hirschhorn, Peter Visscher and colleagues report a meta-analysis of genome-wide association studies for adult height in 253,288 individuals. They identify 697 variants in 423 loci significantly associated with adult height and find that these variants cluster in pathways involved in growth and together explain one-fifth of the heritability for this trait.

Integrated multi-omic analyses using samples from the TRACERx study highlight cross-talk between DNA hypermethylation and genomic lesions in non-small cell lung cancer.

The authors perform meta-analysis of GWAS studies for asthma from multiancestral cohorts. They identify five new loci and find that the asthma-associated loci are enriched near enhancer marks in immune cells.

David van Heel and colleagues report results of a large genome-wide association study of celiac disease. Most of the associated loci contain genes with immune functions, and over half harbor risk variants that are correlated with variation in cis gene expression.

Richard Lifton and colleagues report a genomic analysis of cutaneous T cell lymphoma (CTCL). Their results implicate several pathways in CTCL pathogenesis, including genes involved in T cell activation and apoptosis, NF-κB signaling, chromatin remodeling and DNA damage response.

Fernando Rivadeneira and colleagues in the Genetic Factors for Osteoporosis Consortium report a large-scale meta-analysis identifying new loci associated with bone mineral density (BMD) and risk of fracture. Thirty-two new loci are found to be associated with BMD, and 6 loci confer higher risk for low-trauma bone fracture.

On the Moon, evidence has been found for the preexisting fault reactivation origin (tectonic inversion) of contractional wrinkle ridges in mare basins and the consequent structural control of volcanic eruptions in compressional tectonic settings.

Rinse Weersma, Carl Anderson and colleagues report the results of a trans-ancestry association study of inflammatory bowel disease. They implicate 38 new susceptibility loci, and show that the variance explained by each IBD risk locus is consistent across diverse ancestries, with a few notable exceptions.

Understanding the state of long-lived functional unresponsiveness of T cells, known as T-cell anergy, could help to prevent T-cell-driven autoimmune diseases. This Review discusses the molecular mechanisms underlying this phenomenon and, in particular, the role of E3 ubiquitin ligases.

NFAT2 is a transcription factor that has been linked with chronic lymphocytic leukaemia (CLL), but its functions in CLL manifestation are still unclear. Here the authors show, by analysing mouse CLL models and characterising biopsies from CLL patients, that NFAT2 is an important regulator for the anergic phenotype of CLL.

Kathryn Lunetta and colleagues report a meta-analysis of 22 genome-wide association studies for age at menopause. They identify 13 loci newly associated with age at natural menopause, including several candidate genes with roles in DNA repair and immune function.

Reduced glomerular filtration rate (eGFR) is a hallmark of chronic kidney disease. Here, Pattaro et al. conduct a meta-analysis to discover several new loci associated with variation in eGFR and find that genes associated with eGFR loci often encode proteins potentially related to kidney development.

Measurements from the Chang’e-1 and Chang’e-2 microwave instruments reveal an anomalously hot geothermal source on the Moon that is best explained by a roughly 50-kilometre-diameter granitic system below the geological feature known as Compton–Belkovich.

Craniofacial microsomia is a congenital anomaly that affects the development of the skull. Here, the authors perform a genome-wide association study on patients in China and identify particular loci that provide insights into genetic mechanisms.

Genome-wide association meta-analyses of waist-to-hip ratio adjusted for body mass index in more than 224,000 individuals identify 49 loci, 33 of which are new and many showing significant sexual dimorphism with a stronger effect in women; pathway analyses implicate adipogenesis, angiogenesis, transcriptional regulation and insulin resistance as processes affecting fat distribution.

By combining geophysical and geodetic constraints for different models of the internal structure of the Moon, evidence is provided supporting the lunar mantle overturn scenario and the existence of a solid inner core.

Chronic lymphocytic leukemia is a highly inheritable cancer. Here the authors conduct a metaanalysis of four genome-wide association studies and identify three novel loci located near EOMES, SERPINB6 and LPPassociated with risk of this disease.

The MAGIC investigators report results of a large genome-wide association study meta-analysis to identify common variants influencing fasting glucose homeostasis. They further show that several of the newly discovered loci influencing glycemic traits are also associated with risk of type 2 diabetes.

A series of genetic studies have led to the discovery of novel independent loci and candidate genes associated with red blood cell phenotype; for a proportion of these genes potential single-nucleotide genetic variants are also identified, providing new insights into genetic pathways controlling red blood cell formation, function and pathology.

Lunar impact basins formed during the magma ocean solidification should have formed almost unidentifiable topographic and crustal thickness signatures, thus may escape detection. This result allows for a higher impact flux in the earliest epoch of Earth-Moon evolution.

Danish Saleheen, Benjamin Voight and colleagues perform genome-wide analysis of multi-ancestry cohorts to identify genetic associations with type 2 diabetes (T2D) and coronary heart disease (CHD). They find novel loci and show that 24% of T2D loci are also associated with CHD and that greater genetic risk of T2D increases risk of CHD.

A genome-wide association study and Metabochip meta-analysis of body mass index (BMI) detects 97 BMI-associated loci, of which 56 were novel, and many loci have effects on other metabolic phenotypes; pathway analyses implicate the central nervous system in obesity susceptibility and new pathways such as those related to synaptic function, energy metabolism, lipid biology and adipogenesis.

One way of discovering genes with key roles in cancer development is to identify genomic regions that are frequently altered in human cancers. Here, high-resolution analyses of somatic copy-number alterations (SCNAs) in numerous cancer specimens provide an overview of regions of focal SCNA that are altered at significant frequency across several cancer types. An oncogenic function is also found for the anti-apoptosis genes MCL1 and BCL2L1, which reside in amplified genome regions in many cancers.

A genome-wide association meta-analysis study here shows novel genetic loci to be associated to body fat percentage, and describes cross-phenotype association that further demonstrate a close relationship between adiposity and cardiovascular disease risk.

Stuart Macregor, Tien Wong and colleagues report meta-analyses that identify 16 new loci associated with central corneal thickness. They also identify two loci associated with risk of developing keratoconus, a common corneal ectasia.

John Chambers and colleagues report a genome-wide association study for markers of liver function. They identify 42 loci associated with concentrations of one or more liver enzymes in plasma, and use a range of functional genomic analyses to suggest candidate genes at these loci.

This very large genome-wide association study identifies hundreds of new genetic variants influencing adult height in at least 180 loci enriched for genes involved in skeletal growth defects. The results show that the likely causal gene is often located near the most strongly associated variant, that many loci have multiple independently associated variants and that associated variants are enriched for likely functional effects on genes.

Miles Parkes and colleagues report results of a large genome-wide association meta-analysis and replication study for Crohn's disease. They identify 30 new susceptibility loci for this inflammatory bowel disease and implicate several interesting candidate genes in disease pathogenesis.

John Rioux and colleagues report results of a large genome-wide association meta-analysis and follow-up study of ulcerative colitis. They identify 29 new risk loci for this inflammatory disease and show that many risk loci are shared between ulcerative colitis and Crohn's disease.

John Perry and colleagues report the results of a large genome-wide association study meta-analysis to identify variants influencing age at natural menopause. They identify 54 independent signals and find enrichment near genes involved in delayed puberty and DNA damage response.

Carl Anderson and colleagues report a genome-wide association study identifying 13 new susceptibility loci for primary biliary cirrhosis, a chronic autoimmune liver disease.

NFAT transcription factors are expressed by most immune cells and have critical roles in regulating immune responses. This Review describes recent insights into the NFAT-mediated regulation of distinct immune cells and details our increasing understanding of the importance of the NFAT family during tumorigenesis.

Phylogenetically informed predictions account for phylogenetic relationships among species while predicting unknown trait values. Here, the authors critically compare this approach with equations derived from phylogenetic generalised least squares and ordinary least squares, demonstrating its improved performance across diverse datasets.

ctDNA is a useful tool for the diagnosis of cancer, however, it is usually focused on targeted deep sequencing. Here, the authors develop a methodology to assess TET-assisted pyridine borane whole-genome sequencing data for cancer detection without a matched biopsy.