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An analysis of 16 health-related quantitative traits in approximately 350,000 individuals reveals statistically significant associations between genome-wide homozygosity and four complex traits (height, lung function, cognitive ability and educational attainment); in each case increased homozygosity associates with a decreased trait value, but no evidence was seen of an influence on blood pressure, cholesterol, or ten other cardio-metabolic traits.

Stratified medicine promises to tailor treatment for individual patients, however it remains a major challenge to leverage genetic risk data to aid patient stratification. Here the authors introduce an approach to stratify individuals based on the aggregated impact of their genetic risk factor profiles on tissue-specific gene expression levels, and highlight its ability to identify biologically meaningful and clinically actionable patient subgroups, supporting the notion of different patient ‘biotypes’ characterized by partially distinct disease mechanisms.

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.

Using a battery of statistical tools, Alagöz et al. examine the genetic overlap between dyslexia and rhythm impairment and shed light on how the genome influences the neural bases of human language and musicality.

Multi-ancestry genome-wide association analyses identify new risk loci for Parkinson’s disease, and fine-mapping and co-localization analyses implicate candidate genes whose expression is associated with disease susceptibility.

Rulla Tamimi and colleagues report a meta-analysis of five genome-wide association studies for percent mammographic density. They identify an associated locus at ZNF365, which has also been associated with susceptibility to breast cancer.

Exome-wide sequencing studies of populations in Finland identified 26 deleterious alleles associated with 64 quantitative traits that are clinically relevant to cardiovascular and metabolic diseases.

Cognitive function is associated with health and important life outcomes. Here, the authors perform a genome-wide association study for general cognitive function in 300,486 individuals and identify genetic loci that implicate neural and cell developmental pathways in this trait.

A study of genetic associations identifies 46 new loci associated with alcohol consumption. By assessing their function and potential pleiotropy, the authors suggest genetic mechanisms that are shared with neuropsychiatric disorders, including schizophrenia.

Here 106 genomic loci associated with age at menarche, a marker of puberty timing in females, are identified; these loci show enrichment for genes involved in nuclear hormone receptor function, body mass index, and rare disorders of puberty, and for genes located in imprinted regions, with parent-of-origin specific effects at several loci.

Andrew Morris, Mark McCarthy, Michael Boehnke and colleagues report a meta-analysis of genome-wide association studies for type 2 diabetes, including 26,488 cases and 83,964 controls from populations of European, east Asian, south Asian and Mexican and Mexican American ancestry. They identify seven loci newly associated with type 2 diabetes and examine the genetic architecture of disease across populations.

Psoriasis is an immune-mediated skin disease with a complex genetic architecture. Here, Elder and colleagues identify 16 novel psoriasis susceptibility loci using GWAS meta-analysis with a combined effective sample size of over 39,000 individuals.

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.

Susceptibility to infectious diseases is, among others, influenced by the genetic landscape of the host. Here, Tian and colleagues perform genome-wide association studies for 23 common infections and find 59 risk loci for 17 of these, both within the HLA region and non-HLA loci.

Individual SNPs have small effects on anthropometric traits, yet the impact of CNVs has remained largely unknown. Here, Kutalik and co-workers perform a large-scale genome-wide meta-analysis of structural variation and find rare CNVs associated with height, weight and BMI with large effect sizes.

Vitamin D deficiency is associated with multiple human pathologic conditions. In a genome-wide association study of 79,366 individuals, Jiang et al. replicate four and identify two new genetic loci for serum levels of 25-hydroxyvitamin D and find evidence for a shared genetic basis with autoimmune diseases.

David Hinds and colleagues report results of a genome-wide association meta-analysis of self-reported allergy. They identify 16 shared susceptibility loci for allergic traits, including 8 loci previously associated with asthma.

A genome-wide association study in 293,723 individuals identifies 74 genetic variants associated with educational attainment, which, although only explaining a small proportion of the variation in educational attainment, highlights candidate genes and pathways for further study.

Circadian rhythms and related behaviours vary across individuals. Here, a large genome-wide association study reveals common single nucleotide variants influencing whether an individual reports as being a ‘morning person’ by identifying 15 significant loci, including 7 near known circadian genes.

The majority of published GWAS was performed in European ancestry populations. Here, Kuchenbaecker et al., test to which extent lipid loci are shared and find that the major lipid loci are mostly transferrable between Europeans and Asians while there are notable exceptions for African populations.

Kyle Gaulton, Mark McCarthy, Andrew Morris and colleagues report fine mapping and genomic annotation of 39 established type 2 diabetes susceptibility loci. They find that the set of potential causal variants is enriched for overlap with FOXA2 binding sites in human islet and liver cells, and they show that a likely causal variant near MTNR1B increases FOXA2-bound enhancer activity, providing a molecular mechanism to explain the effect of this locus on disease risk.

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.

Over 170 susceptibility loci have been identified by genome-wide association studies in breast cancer. Here, the authors interrogated the role of risk-associated variants from non-breast tissue, and using expression quantitative trait loci, identify potential target genes of known breast cancer susceptibility variants, as well as 11 regions not previously known to be associated with breast cancer risk.

A meta-analysis of genome-wide association studies of phenotypic variation for height and body mass index in human populations using 170,000 samples shows that one single nucleotide polymorphism at the FTO locus, which is associated with obesity, is also associated with phenotypic variation.

Multi-ancestry genome-wide association analyses for birth weight in 153,781 individuals identified 60 genomic loci in which birth weight and fetal genotype were associated and found an inverse genetic correlation between birth weight and cardiometabolic risk.

Using a sample of more than 1 million individuals, Hatoum et al. identify genomic loci associated with general and substance-specific addiction risk.

Sexual dimorphism in genetic vulnerability to schizophrenia, systemic lupus erythematosus and Sjögren’s syndrome is linked to differential protein abundance from alleles of complement component 4.

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.

TH1760 is a first-in-class, potent, selective and cell-active inhibitor against human NUDT15, which sensitizes cells to 6-thioguanine treatment. TH1760 represents a valuable tool for deciphering the enigmatic functions of NUDT15.

NUDIX hydrolases are an important family of nucleotide-metabolizing enzymes. Here, the authors identify potent, small molecule inhibitors of NUDT5, which is implicated in ADP-ribose and 8-oxo-guanine metabolism, and confirm its role in gene regulation and proliferation in breast cancer cells.

Andrew Singleton and colleagues report a large-scale meta-analysis of genome-wide association data in Parkinson's disease using over 13,000 cases and 95,000 controls plus additional samples for replication. They identify 6 new risk loci and replicate 28 independent risk variants for Parkinson's disease across 24 loci.

Vincent Jaddoe and colleagues report a genome-wide association study for infant head circumference. They identify variants in SBNO1 and near HMGA2 that are associated with this phenotype.

Contrary to the view that urbanization is a major driver of the global rise in obesity, the global increase in body-mass index is shown to be mostly due to increases in the body-mass indexes of rural populations.

Meta-analysis of genome-wide association studies for cognitive ability identifies 190 new loci and implicates 939 new genes related to neurogenesis, neuron differentiation and synaptic structure.

Mark McCarthy and colleagues report a genome-wide association study of birth weight. They identified two loci, in ADCY5 and near CCNL1, that are associated with birth weight and explain 0.3% and 0.1% of the variance in birth weight, respectively.

Relatives of patients with amyotrophic lateral sclerosis have an unexpectedly high incidence of schizophrenia. Here, the authors show a genetic link between the two conditions, suggesting shared neurobiological mechanisms.

In this Review, the authors provide an overview of the evidence for daily, multi-day and yearly cycles in epileptic brain activity. They also discuss advances in our understanding of the mechanisms underlying these cycles and the potential clinical applications of this knowledge.

The transcription factor DAF-16/FOXO is a downstream effector of insulin/insulin-like growth factor signaling and plays an important role in stress resistance and longevity. Here, the authors show that DAF-16/FOXO can form a complex with HLH-30/TFEB to synergistically regulate transcription of target genes in response to certain stress stimuli.

The first crystal structures of complexes between synaptotagmin-1 and neuronal SNARE, bound to either Ca²⁺ or Mg²⁺, are described, and show that Ca²⁺-triggered neurotransmitter release relies on a large, Ca²⁺-independent interface.

Rachel Freathy and colleagues report results of a large-scale genome-wide association study of birth weight. They identify four loci newly associated with this trait and find overlap between birth weight–associated loci and those influencing adult height and metabolism.

Human population genomic studies, including whole‐genome sequencing, were undertaken to identify determinants of bone mineral density (BMD), a major predictor of osteoporotic fractures. Non‐coding variants with large effects on BMD and fractures were identified near the EN1 locus and mouse studies confirmed this gene has an important role in skeletal biology.

Nilesh Samani and colleagues report a meta-analysis of genome-wide association studies for mean leukocyte telomere length in 37,684 individuals, with replication of selected variants in an additional 10,739 individuals. They identify seven loci associated with mean telomere length, including two that have been associated with several cancers, and also find that alleles associated with shorter telomere length were associated with a higher risk of coronary artery disease.