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Francesco Cucca, David Schlessinger, John Novembre, Gonçalo Abecasis and colleagues present sequencing-based whole-genome association analyses for stature in Sardinia and identify two variants that lead to reduced height. Their findings suggest that shorter stature was selected for in Sardinia.

Richard Watanabe and colleagues of the MAGIC consortium report meta-analyses of genome-wide association studies to glucose levels two hours after an oral glucose challenge. They identify variants in GIPR associated with glucose and insulin responses.

Gonçalo Abecasis, Francesco Cucca, David Schlessinger, Serena Sanna and colleagues report ~17.6 million genetic variants from whole-genome sequencing of 2,120 Sardinians. They assess the impact of these variants on circulating lipid levels and five inflammatory biomarkers.

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.

Tasha Fingerlin, David Schwartz and colleagues report a genome-wide association study of fibrotic idiopathic interstitial pneumonia. Their results confirm known risk variants at MUC5B and TERT and identify several new regions associated with disease susceptibility.

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 genetic architecture underlying Sjögren’s syndrome is not fully understood. Here, the authors perform a genome-wide association study to identify 10 new genetic risk regions, implicating genes involved in immune and salivary gland function.

Andre Franke and colleagues report a genome-wide association study for psoriasis vulgaris in a German cohort with replication in German and North American psoriasis cohorts. They identify variants in TRAF3IP2, encoding a protein involved in IL-17 mediated T-cell immune response, associated with psoriasis.

Abnormal PR interval duration is associated with risk for atrial fibrillation and heart block. Here, van Setten et al. identify 44 PR interval loci in a genome-wide association study of over 92,000 individuals and find genetic overlap with QRS duration, heart rate and atrial fibrillation.

The Genetic Association Information Network (GAIN) is a public-private partnership established to investigate the genetic basis of common diseases through a series of collaborative genome-wide association studies. GAIN has used new approaches for project selection, data deposition and distribution, collaborative analysis, publication and protection from premature intellectual property claims. These demonstrate a new commitment to shared scientific knowledge that should facilitate rapid advances in understanding the genetics of complex diseases.

Patrick Ellinor and colleagues report a meta-analysis of genome-wide association studies for atrial fibrillation in European populations. They identify six newly associated loci, four of which were replicated in a Japanese study.

Analysis of blood pressure data from the Million Veteran Program trans-ethnic cohort identifies common and rare variants, and genetically predicted gene expression across multiple tissues associated with systolic, diastolic and pulse pressure in over 775,000 individuals.

Ashley Winslow, Roy Perlis, David Hinds and colleagues report the identification of 15 genetic loci associated with risk of major depressive disorder in individuals of European descent. They find that several loci are also associated with risk of other psychiatric traits, including schizophrenia and neuroticism.

A genome-wide association meta-analysis study of blood lipid levels in roughly 1.6 million individuals demonstrates the gain of power attained when diverse ancestries are included to improve fine-mapping and polygenic score generation, with gains in locus discovery related to sample size.

Here, the analysis of 'HapMap 3' is reported — a public data set of genomic variants in human populations. The resource integrates common and rare single nucleotide polymorphisms (SNPs) and copy number polymorphisms (CNPs) from 11 global populations, providing insights into population-specific differences among variants. It also demonstrates the feasibility of imputing newly discovered rare SNPs and CNPs.

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.

Circulating lipoprotein(a) is an important risk factor for cardiovascular disease and shows variability between different ethnic groups. Here, Zekavat et al. perform whole-genome sequencing in individuals of European and African ancestries and find ancestry-specific genetic determinants for lipoprotein(a) levels.

Paul Pharoah, Joellen Schildkraut, Thomas Sellers and colleagues report a meta-analysis of genome-wide association studies for epithelial ovarian cancer and genotyping using the iCOGS array in 18,174 cases and 26,134 controls from 43 studies from the Ovarian Cancer Association Consortium. They identify three new ovarian cancer susceptibility loci, including one specific to the serous subtype, and their integrated molecular analysis of genes and regulatory regions at these loci suggests disease mechanisms.

Patrick Ellinor and colleagues report a genome-wide association study identifying variants in KCNN3 associated to lone atrial fibrillation.

Janey Wiggs, Jonathan Haines and colleagues identify three new susceptibility loci for primary open-angle glaucoma. The association signals map near genes implicated in ocular development (FOXC1), neurodegeneration (ATXN2) and mitochondrial function (TXNRD2).

Florent Soubrier and colleagues report a genome-wide association study of pulmonary arterial hypertension. They identify a susceptibility locus near CBLN2 associated with a twofold elevated risk of developing this life-threatening disease.

Goncalo Abecasis and colleagues report identification of a rare coding variant in the complement 3 gene that is associated with age-related macular degeneration.

Claudia Langenberg, James Meigs and colleagues apply a joint meta-analysis approach that accounts for differences in body mass index to identify variants associated with glycemic traits. They report six new loci associated with fasting insulin levels and provide insights into the genetic basis of insulin resistance.

Genome-wide meta-analysis of SARS-CoV-2 susceptibility and severity phenotypes in up to 756,646 samples identifies a rare protective variant proximal to ACE2. A 6-SNP genetic risk score provides additional predictive power when added to known risk factors.

A dataset of coding variation, derived from exome sequencing of nearly one million individuals from a range of ancestries, provides insight into rare variants and could accelerate the discovery of disease-associated genes and advance precision medicine efforts.

Luca Lotta, Robert Scott, Stephen O’Rahilly, Claudia Langenberg, David Savage, Nicholas Wareham, Inês Barroso and colleagues identify 53 genomic regions associated with insulin resistance phenotypes. Their findings suggest that limited storage capacity of peripheral adipose tissue is an important etiological component in insulin-resistant cardiometabolic disease and highlight genes and mechanisms underpinning this link.

John Chambers and colleagues identify common variants at four loci associated with serum creatinine levels, a marker of kidney function. Their findings provide insight into the pathways underlying susceptibility to chronic kidney disease.

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.

Genome-wide association studies have only revealed a handful of genetic loci for longevity. Here, in a case–control design based on phenotype definitions of individuals surviving at or beyond the age corresponding to the 90th and 99th survival percentile, the authors report two additional loci located in the APOE locus and near GPR78.

MultiSTAAR provides a general and flexible statistical framework for functionally informed multi-trait rare variant analysis of biobank-scale sequencing studies by jointly analyzing multiple traits and incorporating annotation information.

Francesco Cucca, Stephen Montgomery and colleagues identify regulatory variants that influence gene expression and splicing using whole-genome and transcriptome sequence data from 624 Sardinians. They find a high frequency of splicing and expression quantitative trait loci near genes involved in malarial resistance and multiple sclerosis.

Statins are effectively used to prevent and manage cardiovascular disease, but patient response to these drugs is highly variable. Here, the authors identify two new genes associated with the response of LDL cholesterol to statins and advance our understanding of the genetic basis of drug response.

Aarno Palotie and colleagues present results of a large genome-wide association study of migraine. They identified significant associations at 38 distinct loci and found enrichment for genes expressed in vascular and smooth muscle tissues.

Ruth Loos and colleagues use genome-wide association to identify common variants influencing body fat percentage. Unexpectedly, they show that a body-fat–decreasing allele near IRS1 is associated with an impaired metabolic profile, including increased risk of type 2 diabetes and coronary artery disease.

The goals, resources and design of the NHLBI Trans-Omics for Precision Medicine (TOPMed) programme are described, and analyses of rare variants detected in the first 53,831 samples provide insights into mutational processes and recent human evolutionary history.

Exome-sequencing analyses of a large cohort of patients with type 2 diabetes and control individuals without diabetes from five ancestries are used to identify gene-level associations of rare variants that are associated with type 2 diabetes.

Genome-wide analyses identify variants in B3GALT5 and ST6GAL1 associated with influenza susceptibility. Knockdown of ST6GAL1 in cell culture reduces influenza infectivity, likely by interfering with the glycoprotein modifications required for viral entry.

Philip De Jager and colleagues report results of a large genome-wide association and replication study for multiple sclerosis. The work uncovers three new susceptibility loci for MS, including common and rare variants at TNFRSF1A and common variants at IRF8 and CD6.

STAAR is a powerful rare variant association test that incorporates variant functional categories and complementary functional annotations using a dynamic weighting scheme based on annotation principal components. STAAR accounts for population structure and relatedness and is scalable for analyzing large whole-genome sequencing studies.

Association analyses in over 1 million individuals identify 535 new loci influencing blood pressure traits. The results provide new insights into blood pressure regulation and highlight shared genetic architecture between blood pressure and lifestyle exposures.

Richard Spritz and colleagues report genome-wide association analyses identifying 13 new susceptibility loci for generalized vitiligo. Their functional pathway analysis shows that many vitiligo susceptibility loci encode immunoregulatory proteins or melanocyte components.

Caroline Klaver and colleagues report a genome-wide association study for myopia and refractive error in the general population, identifying a susceptibility locus at 15q14.

Christian Fuchsberger, Gonçalo Abecasis and colleagues describe a new web-based imputation service that enables rapid imputation of large numbers of samples and allows convenient access to large reference panels of sequenced individuals. Their state space reduction provides a computationally efficient solution for genotype imputation with no loss in imputation accuracy.

Caroline Fox and colleagues report results of a genome-wide association study to identify common variants associated with indices of renal function. They show that variants at UMOD, a gene previously implicated in rare monogenic forms of kidney disease, are associated with risk of chronic kidney disease in the general population.

Basal cell carcinoma is a common skin lesion and the risk loci for this cancer are beginning to be understood. In this study, the authors conduct a two-stage genome-wide association study and confirm known risk loci and identify an additional 14 loci.

Studies on the ‘epigenetic clock’, a recently identified ageing biomarker, suggest that pathology might be linked to tissue-specific accelerated ageing. Here, the authors investigate ageing in the human brain and identify genetic loci associated with accelerated ageing in different brain regions.