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Polygenic scores for body mass index and obesity constructed using data from 5 million people with different ancestries were associated with distinct weight gain trajectories from early childhood to adulthood.

The self renewal of hematopoietic stem cells is regulated by the bone marrow microenvironment. Whereas previous studies have focused on the role of osteoblasts, Ingrid Winkler et al. now show that bone marrow endothelial cells in the so-called 'vascular niche' contribute to this regulation by directly inducing HSC proliferation. In mice, deficiency or antagonism of the endothelial-specific adhesion protein E-selectin promotes HSC quiescence and self renewal. These findings may point to a new treatment strategy for preserving HSC function in patients undergoing chemotherapy.

A transancestral exome-wide association study for body-fat distribution identifies protein-coding variants that are significantly associated with waist-to-hip ratio adjusted for body mass index.

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.

Multiancestry genome-wide association analyses identify new risk loci for stroke and stroke subtypes. Fine mapping and bioinformatics analyses of these risk loci point to mechanisms not previously implicated in stroke pathophysiology.

Genome-wide association studies (GWAS) have become a key tool to discover genetic markers for complex traits; however, environmental factors that interact with genes are rarely considered. Here, the authors conduct a GWAS of obesity traits, and find that smoking may alter genetic susceptibilities.

A large genome-wide association study of more than 5 million individuals reveals that 12,111 single-nucleotide polymorphisms account for nearly all the heritability of height attributable to common genetic variants.

The cell adhesion molecule E-selectin regulates haematopoietic stem cell self-renewal in the bone marrow vascular niche. Here, the authors show E-selectin adhesion directly induces survival signaling in acute myeloid leukaemia and therapeutic inhibition improves chemotherapy outcomes in mice.

The hippocampus in mammalian brain varies in size across individuals. Here, Hibar and colleagues perform a genome-wide association meta-analysis to find six genetic loci with significant association to hippocampus volume.

In a GWAS study of 32,438 adults, the authors discovered five novel loci for intracranial volume and confirmed two known signals. Variants for intracranial volume were also related to childhood and adult cognitive function and to Parkinson's disease, and enriched near genes involved in growth pathways, including PI3K-AKT signaling.

Anticancer cytotoxic drugs also kill normal progenitors found in rapidly regenerating tissues, resulting in prolonged hematopoietic insufficiency. Chemotherapy-induced toxicity of the nerves that regulate bone marrow niches required for regeneration of hematopoietic stem cells (HSCs) is involved in this insufficiency, which suggests that co-administration of neuroprotective agents may protect HSCs from the toxic effects of drugs such as cisplatin and vincristine (pages 695–703).

The authors defined a roadmap for investigating the genetic covariance between structural or functional brain phenotypes and risk for psychiatric disorders. Their proof-of-concept study using the largest available common variant data sets for schizophrenia and volumes of several (mainly subcortical) brain structures did not find evidence of genetic overlap.

Cecilia Lindgren and colleagues report results of a large-scale genome-wide association study for waist-to-hip ratio, a measure of body fat distribution. They identify 13 new loci associated with this trait, several of which show stronger effects in women than in men.

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.

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.

In this compassionate use study, treatment of adult patients with H3K27M-mutant diffuse midline glioma with a long peptide vaccine targeting H3K27M led to vaccine-induced peripheral T cell immune responses and encouraging clinical efficacy in the majority of patients, including a durable complete response.

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.

Erik Ingelsson and colleagues report a large-scale genome-wide meta-analysis for associations to the extremes of anthropometric traits, including body mass index, height, waist-to-hip ratio and clinical obesity. They identify four loci newly associated with height and seven loci newly associated with clinical obesity and find overlap in the genetic structure and distribution of variants identified for these extremes of the trait distributions and for the general population.

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.

Data from over 700,000 individuals reveal the identity of 83 sequence variants that affect human height, implicating new candidate genes and pathways as being involved in growth.

Past genome-wide associate studies have identified hundreds of genetic loci that influence body size and shape when examined one trait at a time. Here, Jeff and colleagues develop an aggregate score of various body traits, and use meta-analysis to find new loci linked to body shape.

Exome-wide analysis identifies rare and low-frequency coding variants associated with body mass index. Gene-based meta-analysis and functional studies implicate 13 genes, eight of which are novel, and neuronal pathways as factors in human obesity.

Paul Thompson and colleagues report a genome-wide association study for hippocampal, intracranial and total brain volume. They identify a locus at 12q24 associated with hippocampal volume and a locus at 12q14 associated with intracranial volume.

Genome-wide association studies are used to identify common genetic variants that affect the structure of selected subcortical regions of the human brain; their identification provides insight into the causes of variability in brain development and may help to determine mechanisms of neuropsychiatric dysfunction.

Carotid intima-media thickness (cIMT) and plaque are associated with subclinical atherosclerosis and coronary heart disease (CHD). Here, the authors identify and prioritize genetic loci for cIMT and plaque by GWAS and colocalization approaches and further demonstrate genetic correlation with CHD and stroke.

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.

Keri Monda, Kari North, Christopher Haiman and colleagues report a meta-analysis of GWAS for body mass index that is composed of 39,144 individuals of African ancestry, followed by further genotyping in 32,268 individuals of African ancestry. The study also includes analysis of publicly available data from the GIANT consortium of ~124,000 individuals of European ancestry. The paper reports evidence for two new loci near GALNT10 and MIR148A.

Using whole-genome data for single-nucleotide polymorphism and results from genome-wide association studies, the authors show that people’s preference for pairing with those with similar phenotypic traits has genetic causes and consequences.