Search

Burden testing in three large European ancestry cohorts identifies new risk genes for a number of common cancer types, including pan-cancer protective variants in AURKB and breast cancer protective variants in PPP1R15A.

The corneal endothelium is crucial for proper vision. Here, Ivarsdottir et al. perform genome-wide association studies for various corneal endothelial cell measurements and find that an intergenic variant near ANAPC1 explains 24% of the variance of endothelial cell density and associates with corneal hysteresis.

Analyses focusing on protein-truncating variants from 106,973 women from in the UK Biobank identify variants in genes that reinforce the link between reproductive lifespan in women and cancer risk in both sexes.

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.

Holm, Ivarsdottir, Olafsdottir et al. compare symptoms and physical measures between Icelanders post SARS-CoV-2 infection with uninfected controls. From reported symptoms, they estimate the prevalence of long COVID as 7% at a median of 8 months after infection, while objective differences between cases and controls in the physical measures were few.

Analysis of whole-genome sequencing data from Iceland and the UK Biobank identifies an excess burden of rare loss-of-function variants in HECTD2 and AKAP11 in individuals diagnosed with bipolar disorder.

Understanding the underlying pathophysiology of obesity can help prevent this condition. Here, the authors perform a GWAS of BMI in diverse ancestries, finding four missense variants in FRS3 that affect BMI.

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.

Daniel Gudbjartsson, Kari Stefansson and colleagues assess the effect of variants associated with mean fasting glucose levels on the variance in fasting glucose levels. They find that variants that increase both the levels and variance of fasting glucose increase type 2 diabetes risk, whereas those that increase the levels but reduce the variance do not.

Here, the authors conduct a GWAS for autoimmune thyroid disease, finding 225 loci including a start codon variant in LAG3 that confers a 3.4-fold risk of autoimmune thyroid disease and reduces expression and plasma levels of LAG−3.

Genome-wide association analyses using parental and offspring genotypes provide insights into fetal and maternal genetic effects on fetal growth. The results show that maternal and fetal genomes influence birth weight through distinct mechanisms.

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.

A predicted loss-of-function germline mutation in FLT3 causes a reduction in full-length FLT3, with a compensatory increase in the levels of FLT3 ligand, leading to increased risk of autoimmune thyroid disease.

Diagnosis and classification of peripheral neuropathy (PN) is facilitated by nerve conduction (NC) studies. Here, Bjornsdottir et al. find a low-frequency PRPH splice-donor variant that associates with NC amplitude and neurological assessment of recalled PRPH variant carriers reveals increased risk of a mild sensory-negative PN.

While the consequences of homozygous loss of function variants have been studied, the effect of missense variants is less understood. Here, the authors identify pathogenic genotypes through an observed deficit of homozygous carriers of missense variants in a population, elucidating previously unexplained recessive disease and miscarriage.

Mutations in genes encoding NAPDH oxidase subunits are known to be causative for the primary immunodeficiency chronic granulomatous disease (CGD). Here, the authors identify CYBC1 mutations in patients with CGD and show that CYBC1 is important for formation of the NADPH complex and respiratory burst.

A GWAS in Iceland reveals that variants in inner nuclear membrane proteins are associated with nuclear morphology of granulocytes and band neutrophil fraction.

A meta-analysis of GWAS studies identified nine sequence variants associated with urticaria. These results and multi-omics analyses support the role of mast cell activation and type 2 immune response in urticaria.

A study of 768 convalescent SARS CoV-2-infected and 500 uninfected Icelanders reveals broad and stable T-cell responses 3-8 months from infection. HLA alleles, disease severity, and age contribute to the heterogeneity of cellular immunity.

Rosa Thorolfsdottir et al. report a genome-wide association study of atrial fibrillation in 29,502 cases and 767,760 controls from Iceland and the UK Biobank. They identify a significant association with coding variants in RPL3L, the first ribosomal gene implicated in atrial fibrillation, and MYZAP, an intercalated disc gene.

Astros Skuladottir et al. conducted a genome-wide association study on 48,072 vertigo cases and 894,541 controls from four populations with European ancestries. They identified six common variants associated with vertigo, thereby providing further insight into the etiology of vestibular disorders.

Gudjon Oskarsson et al. report the association of a rare variant in the erythropoietin (EPO) receptor gene, EPOR, with serum EPO levels in the Icelandic population. The variant leads to a truncation of EPO-R without an effect on hemoglobin levels, indicating a possible feedback mechanism in the generation of red blood cells.

Gudjon Oskarsson et al. report a genome-wide association study of hemoglobin concentration in more than 680,000 individuals from Iceland and the UK. They identify six novel rare coding variants at the ACO1 locus that associate with either increased or decreased hemoglobin concentration, two of which have large and opposite effects.

Eiriksdottir et al. use a temporal proteomic dataset from over 22,000 Icelandic individuals to identify predictors and predict all-cause mortality. Their findings suggest that the plasma proteome may be of value in general health screening for risk of death.