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Structural variants (SVs) are prevalent in genomes of the general population. Here, Guryev and The Genome of the Netherlands Consortium describe the reference panel of haplotype-resolved SVs from 769 individuals from 250 Dutch families and show its utility for studying heritable traits.

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.

The immune response to pathogens varies substantially among humans. Netea and colleagues show that integration of multi-omics data and deep phenotyping enables prediction of cytokine production in responses to pathogens.

Identification of causal drivers behind expression is essential for understanding gene function. Here authors develop a method for the large-scale inference of gene–gene interactions in observational population genomics data and characterize a network of trans-effects for 6600 genes.

A calixarene–protein host–guest complex has been characterized in detail by using a combination of NMR spectroscopy and X-ray crystallography. The water-soluble sulfonato-calix[4]arene binds to cytochrome c at various lysine residues to yield a dynamic complex. This interaction may serve to facilitate crystallization by mediating protein–protein contacts.

Martin Tobin and colleagues report a meta-analysis of 23 genome-wide association studies for pulmonary function. They identify 16 loci newly associated with variation in two cross-sectional measures of lung function, used to define airway obstruction and to grade the severity of obstruction.

DNA methylation is critically involved in X chromosome inactivation (XCI) and dosage compensation, yet some X-chromosomal genes escape XCI. Here, Lujik et al. identify three autosomal genetic loci that associate with differential DNA methylation near genes that variably escape XCI in females.

Plasma levels of liver enzymes provide insights into hepatic function and related diseases. Here, the authors perform a genome-wide association study on three liver enzymes, identifying genetic variants associated with their plasma concentration as well as links to metabolic and cardiovascular diseases.

Thyroid dysfunction is a common public health problem and associated with cardiovascular co-morbidities. Here, the authors carry out genome-wide meta-analysis for thyroid hormone (TH) levels, hyper- and hypothyroidism and identify SLC17A4 as a TH transporter and AADAT as a TH metabolizing enzyme.

Cristen Willer and colleagues report genome-wide association analyses for blood lipid levels in 188,578 individuals. They identify 62 loci newly associated with blood lipid levels, refine the association signals at 12 loci and examine associations with cardiovascular and metabolic traits.

The results of genome-wide association studies are combined with quantitative interaction proteomics to narrow down the list of putative causal disease genes and filter modest association signals.

Sekar Kathiresan and colleagues examine 185 common variants using a modified mendelian randomization approach and provide evidence supporting a causal role of triglyceride-rich lipoproteins in the development of coronary artery disease.

Differential impact of genetic and environmental influences on DNA methylation may result in sex- and age-related physiological variation and disease susceptibility. By analysing DNA methylome of 2,603 individuals from twin families, here, the authors establish a catalogue of between-individual variation in DNA methylation.

Blood metabolite levels are under the influence of environmental and genetic factors. Here, Hagenbeek et al. perform heritability estimations for metabolite measures and determine the contribution of known metabolite loci to metabolite levels using data from 40 genome-wide association studies.

Most of the more than 200 known genetic risk loci for inflammatory bowel disease (IBD) reside in regulatory regions. Here, the authors provide eQTL datasets for six circulating immune cell types and ileal, colonic and rectal biopsies to map regulatory modules and identify potential causative genes for IBD.

Richard Trembath and colleagues report a meta-analysis of genome-wide association studies for psoriasis, including 2 cohorts genotyped on the custom Immunochip array, in a total of 10,588 cases and 22,806 controls. They identify 15 new susceptibility loci and refine signals in previously known loci, highlighting a role for innate host defense in susceptibility to psoriasis.

Peter Donnelly and colleagues report a genome-wide association study for Barrett's esophagus, a common premalignant condition associated with stomach acid reflux and predisposing to esophageal adenocarcinoma. They identify two loci associated with susceptibility to Barrett's esophagus.

Eli Stahl and colleagues report results of a genome-wide association study meta-analysis and replication study for rheumatoid arthritis. Their work identifies several new risk loci and highlights genetic overlap with other autoimmune diseases.

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.

Solveig Gretarsdottir, Kari Stefansson and colleagues report a genome-wide association study for abdominal aortic aneurysm. They identified a variant located within the DAB2IP gene on 9q33 associated with risk of developing abdominal aortic aneurysm.

Mark Seielstad and colleagues report results of a large genome-wide association and replication study of ulcerative colitis. The work identifies several new risk loci for this disease and provides further insight into the shared pathogenesis of ulcerative colitis and Crohn's disease.

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.

This Perspective describes different study designs for the genetic analyses of large-scale cohorts, using Dutch cohorts as primary examples, and discusses lessons learned as well as recommendations for future cohort studies.

Soumya Raychaudhuri, Paul de Bakker and colleagues test the non-additive disease contributions of classical HLA alleles to five common autoimmune diseases. In four of the five diseases, they observe highly significant non-additive dominance and interaction effects.

A large-scale epigenome-wide association study identifies changes in DNA methylation associated with body mass index in blood and adipose tissue, and correlates DNA methylation sites with high risk of incident type 2 diabetes.

A meta-analysis of previous genome-wide association studies of Crohn’s disease and ulcerative colitis, the two most common forms of inflammatory bowel disease, with a combined total of more than 75,000 cases and controls, finds that most loci contribute to both phenotypes and other immune-mediated disorders.

Konstantinos Lazaridis, Carl Anderson and colleagues report results of a genome-wide association study of primary sclerosing cholangitis (PSC). They identify four new susceptibility loci for PSC and quantify the correlation of common genetic variation shared between PSC and inflammatory bowel diseases.

Rudolf Fehrmann, Lude Franke and colleagues report a method for capturing the variation present within mammalian transcriptomes in a limited number of 'transcriptional components' and demonstrate widespread correlation between gene copy number and expression levels. The method allows for the inference of candidate gene function and the identification of potential therapeutic targets in cancer.

Murat Gunel and colleagues report a genome-wide association study for intracranial aneurysm and identify risk variants near RBBP8, CNNM and STARD13.

Johannes Schumacher and colleagues report the results of a genetic association study of idiopathic achalasia, a rare motility disorder of the esophagus. They show that common variation in the HLA-DQ region is strongly associated with achalasia risk, implicating immune-mediated processes in this disorder.

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.

Shamil Sunyaev, Paul de Bakker and colleagues report an analysis of 11,020 de novo mutations from the whole-genome sequences of Dutch families sequenced as part of the Genome of the Netherlands project. They identify correlations related to paternal age and genic content and develop an empirical human mutation rate map.

Peter 't Hoen, Lude Franke, Bastiaan Heijmans and colleagues present a combined analysis of methylome and transcriptome data from a large collection of whole-blood samples to infer the downstream effects of disease-associated variants. They identify a large number of trait-associated SNPs influencing methylation of CpG sites in trans, providing insights into the downstream functional effects of many disease-associated variants.