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Here, human genome-wide single-nucleotide polymorphism (SNP) data from more than 15,000 parent–offspring pairs have been used to construct the first recombination maps that are based on directly observed recombination events. The data reveal interesting differences between the sexes: for instance, in males recombination tends to shuffle exons, whereas in females it generates new combinations of nearby genes. Comparison of these maps with others also reveals population differences.

Around 1 in 136 pregnancies is lost due to a pathogenic small sequence variant genotype in the fetus.

Complete human recombination maps are presented that enable exploration of both cross-over and non-cross-over events during meiosis, with the potential to provide insight into the causes of aneuploidies and pregnancy loss.

Microsatellites are tandem repeats of short DNA motifs and represent some of the most polymorphic sites in the genome. Here, the authors report that the human germline microsatellite mutation rate is, in part, under genetic control.

Whole-genome sequencing of monozygotic twins, along with their parents, spouses and children, identifies postzygotic mutations present in the somatic tissue of one twin, but not the other, and characterizes differences in the number and timing of these mutations.

The concentration of SARS-CoV-2 changes during an individual’s infection, and mutations accumulate as viruses are transmitted between people. Here, the authors use data from Iceland to demonstrate how this information can be exploited at the population-level to determine the phase of the epidemic.

Asthma is a common allergic airway disease with significant inter-individual heterogeneity. Here, Olafsdottir et al. report a genome-wide meta-analysis of two large population-based cohorts to identify sequence variants that associate with asthma risk and perform follow-up functional analyses on a protective loss-of-function variant in TNFRSF8.

The effect of sequence variants on phenotypes may depend on parental origin. Here, a method is developed that takes parental origin — the impact of which, to date, has largely been ignored — into account in genome-wide association studies. For 38,167 Icelanders genotyped, the parental origin of most alleles is determined; furthermore, a number of variants are found that show associations specific to parental origin, including three with type 2 diabetes.

To measure selection on variants, whole-genome sequencing of approximately 150,000 individuals from the UK Biobank is used to rank sequence variants by their level of depletion.

Iceland has used four different SARS-CoV-2 vaccines in various combinations. Here, the authors describe differences in the immune responses elicited by different initial/booster vaccine combinations, and then use population-level data to assess the effects of booster doses against Delta and Omicron infection.

A study reports whole-genome sequences for 490,640 participants from the UK Biobank and combines these data with phenotypic data to provide new insights into the relationship between human variation and sequence variation.

Hilma Holm et al. report a rare missense variant MYH6 that is associated with a high risk of sick sinus syndrome in Icelanders. This heart condition is found most often in elderly people and is the most frequent reason a heart pacemaker is implanted.

Augustine Kong and colleagues describe an approach for phasing SNPs into long haplotypes spanning multiple blocks of linkage disequilibrium. The method, termed long-range phasing, can be also used to impute long haplotypes for ungenotyped individuals.

Size and shape of bones are important for height and body shape. Here, Styrkarsdottir et al identify 12 loci in a GWAS for bone area derived from DXA scans and show that these loci associate with other bone-related phenotypes including osteoarthritis, height, bone mineral density and risk of hip fracture.

Bjarni Halldorsson, Kari Stefansson and colleagues use SNP array and whole-genome sequencing data to estimate the meiotic gene conversion rate (G) in humans. They find that G for SNPs is 7.0 conversions/Mb per generation, is 2.17 greater in mothers than in fathers, and increases with maternal age.

Kari Stefansson and colleagues report the whole-genome sequencing of 2,636 individuals from Iceland to a median of 20× coverage, providing a valuable genomic resource for this population isolate. They characterize patterns of genetic variation and population structure and demonstrate the usefulness of this resource for genetic discovery for several disease phenotypes.

Ingileif Jonsdottir, Björn Nilsson, Kari Stefansson and colleagues perform a genome-wide association study for immunoglobulin levels in Icelandic and Swedish cohorts. They find 38 new variants associated with IgA, IgG, IgM or composite immunoglobulin traits and identify candidate genes underlying the regulation of immunoglobulin levels.

Analysis of 1,007 sibling pairs from 251 families identifies 878 de novo mutations shared by siblings at 448 sites. Recurrence probability based on parental somatic mosaicism, sibling sharing, parent of origin, mutation type and genomic position can range from 0.011% to 28.5%.

The genetics of schizophrenia and other mental disorders are complex and poorly understood, and made even harder to study due to reduced reproduction resulting in negative selection pressure on risk alleles. Two independent large-scale genome wide studies of thousands of patients and controls by two international consortia confirm a previously identified locus, but also reveal novel associations. In this study, de novo (spontaneous) copy number variants are reported on chromosomes 1 and 15.

Using a combination of whole-genome sequencing, haplotype sharing and the genealogies of the Icelandic population, Thorunn Rafnar, Kari Stefansson and colleagues identified a rare coding mutation in the gene of a BRCA1-interacting factor, BRIP1, that confers a high relative risk of ovarian cancer.

Whole-genome sequencing data of 14,688 Icelanders, including 1,548 parent–offspring trios, show how the age and sex of parents affect the rate and spectrum of de novo mutations.

Bjarni Halldorsson, Kari Stefansson and colleagues analyze genomic data from 15,219 Icelanders to identify non-repetitive sequences that are missing from the reference genome. They describe 3,791 breakpoint-resolved sequence variants and find overlap with GWAS markers as well as the presence of a proportion of these variants in the chimpanzee genome.

Ingileif Jonsdottir, Kari Stefansson and colleagues show that variants in the HLA class II region contribute to tuberculosis risk in populations of European ancestry. They propose that the associated variants influence disease risk by altering expression of HLA class II molecules presenting protective M. tuberculosis antigens to T cells.

Patrick Sulem, Daniel Gudbjartsson, Bragi Walters and colleagues identify two low-frequency variants associated with serum uric acid levels and gout in the Icelandic population. The variants were discovered by whole-genome sequencing and are associated with two- to threefold differences in disease risk.

Julius Gudmundsson and colleagues report a prostate cancer genome-wide association follow-on study. They report variants at 3q21.3, 8q24.21 and 19q13.2 newly associated to prostate cancer susceptibility and the fine-mapping of the association signal at 11q13.

Hannes Helgason, Kari Stefansson and colleagues report an association study of gastric cancer susceptibility based on whole-genome sequencing in the Icelandic population. They find that loss-of-function variants in ATM confer risk of gastric cancer.

Erna Ivarsdottir et al. report a genome-wide association meta-analysis for age-related hearing loss in the Icelandic and UK populations. They identify 21 novel variants, 13 of which are rare, and reveal a genetic correlation between age-related hearing loss and tinnitus.