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Sebaceous carcinomas (SeC) are cutaneous malignancies that sometimes metastasize and cause death. Here the authors perform whole-exome sequencing on 32 SeC and report distinct mutational classes that may explain cancer ontogeny and clinical outcome.

Similarities in cancers can be studied to interrogate their etiology. Here, the authors use genome-wide association study summary statistics from six cancer types based on 296,215 cases and 301,319 controls of European ancestry, showing that solid tumours arising from different tissues share a degree of common germline genetic basis.

The authors analyzed the whole-exome sequences of over 16,000 individuals and found that very rare variants predicted to disrupt the SETD1A gene confer substantial risk for schizophrenia. Damaging variants in SETD1A were also associated with diverse, severe developmental disorders, providing an important genetic link between schizophrenia and other neurodevelopmental disorders.

Genetic and testing data from England show that the SARS-CoV-2 variant of concern B.1.1.7 has a transmission advantage over other lineages.

Sera from vaccinated individuals and some monoclonal antibodies show a modest reduction in neutralizing activity against the B.1.1.7 variant of SARS-CoV-2; but the E484K substitution leads to a considerable loss of neutralizing activity.

Stig Bojesen, Georgia Chenevix-Trench, Alison Dunning and colleagues report common variants at the TERT-CLPTM1L locus associated with mean telomere length measured in whole blood. They also identify associations at this locus to breast or ovarian cancer susceptibility and report functional studies in breast and ovarian cancer tissue and cell lines.

The Omicron variant evades vaccine-induced neutralization but also fails to form syncytia, shows reduced replication in human lung cells and preferentially uses a TMPRSS2-independent cell entry pathway, which may contribute to enhanced replication in cells of the upper airway. Altered fusion and cell entry characteristics are linked to distinct regions of the Omicron spike protein.

Chronic infection with SARS-CoV-2 leads to the emergence of viral variants that show reduced susceptibility to neutralizing antibodies in an immunosuppressed individual treated with convalescent plasma.

A study of the evolution of the SARS-CoV-2 virus in England between September 2020 and June 2021 finds that interventions capable of containing previous variants were insufficient to stop the more transmissible Alpha and Delta variants.

Whole-genome sequencing and phenotype data sharing are introduced in a national health system to streamline diagnosis and to discover coding and non-coding variants that cause rare diseases.

Fine-mapping of causal variants and integration of epigenetic and chromatin conformation data identify likely target genes for 150 breast cancer risk regions.

A region on chromosome 19p13 is associated with the risk of developing ovarian and breast cancer. Here, the authors genotyped SNPs in this region in thousands of breast and ovarian cancer patients and identified SNPs associated with three genes, which were analysed with functional studies.

In this study, Aggarwal and colleagues perform prospective sequencing of SARS-CoV-2 isolates derived from asymptomatic student screening and symptomatic testing of students and staff at the University of Cambridge. They identify important factors that contributed to within university transmission and onward spread into the wider community.

Post-international travel quarantine has been widely implemented to mitigate SARS-CoV-2 transmission, but the impacts of such policies are unclear. Here, the authors used linked genomic and contact tracing data to assess the impacts of a 14-day quarantine on return to England in summer 2020.

Alison Dunning, Stacey Edwards and colleagues analyze 3,872 common variants across the ESR1 locus in 118,816 women. They find five independent variants within regulatory regions that associate with different breast cancer–related phenotypes and regulate the expression of ESR1, RMND1 and CCDC170.

Exome sequences from the first 49,960 participants in the UK Biobank highlight the promise of genome sequencing in large population-based studies and are now accessible to the scientific community.

Investigation of variation in three cohorts has identified multiple genetic signals associated with the pregnancy-specific liver disorder, intrahepatic cholestasis of pregnancy, giving insight into the disease which can cause preterm birth and stillbirth.

MYC activation can sensitise cells to apoptosis upon glutamine withdrawal. Here the authors show that MYC activation enhances global transcription and translation that creates a metabolic demand, while glutamine limitation causes a metabolic demand and supply imbalance through loss of TCA energetics and thus, sensitises cells to apoptosis.

Whole-genome sequencing analysis of individuals with primary immunodeficiency identifies new candidate disease-associated genes and shows how the interplay between genetic variants can explain the variable penetrance and complexity of the disease.

Durable agonism of NPR1 achieved with a novel investigational monoclonal antibody could mirror the positive hemodynamic changes in blood pressure and heart failure identified in humans with lifelong exposure to NPR1 coding variants.

The catalytic enantioconvergent nucleophilic fluorination of alkyl halides using inexpensive alkali metal fluorides is a persistent challenge. Now this has been achieved by synergistic hydrogen bonding phase-transfer catalysis combining a chiral bis-urea hydrogen bond donor and an onium salt.

Better analytical methods are needed to extract biological meaning from genome-wide association studies (GWAS) of psychiatric disorders. Here the authors take GWAS data from over 60,000 subjects, including patients with schizophrenia, bipolar disorder and major depression, and identify common etiological pathways shared amongst them.

Douglas Easton, Per Hall and colleagues report meta-analyses of genome-wide association studies for breast cancer, including 10,052 cases and 12,575 controls, followed by genotyping using the iCOGS array in an additional 52,675 cases and 49,436 controls from studies within the Breast Cancer Association Consortium (BCAC). They identify 41 loci newly associated with susceptibility to breast cancer.

PFA tumours express high levels of EZHIP (also known as CXORF67). Here the authors find that EZHIP directly interacts with the active site of EZH2 and is a competitive inhibitor of PRC2 and that EZHIP gives rise to H3K27me3 genomic profile similar to the K27M oncohistone.

Jeffrey Barrett, Tarjinder Singh and colleagues present a meta-analysis of rare coding variants and copy number variants in a large collection of schizophrenia cases and controls, combined with de novo mutation data from family trios. They find that rare, damaging variants contribute to risk of schizophrenia both with and without intellectual disability and that there is overlap between genetic risk for schizophrenia and other neurodevelopmental disorders.

The Vertebrate Genome Project has used an optimized pipeline to generate high-quality genome assemblies for sixteen species (representing all major vertebrate classes), which have led to new biological insights.

Roger Milne and colleagues conduct a genome-wide association study for estrogen receptor (ER)-negative breast cancer combined with BRCA1 mutation carriers in a large cohort. They identify ten new risk variants and find high genetic correlation between breast cancer risk for BRCA1 mutation carriers and risk of ER-negative breast cancer in the general population.

In the US, up to 30% of colon cancers exhibit familial clustering and 3–5% are associated with high-risk, inherited colon cancer syndromes. The authors of this Review discuss the clinical presentation and genetics of the major inherited colon cancer syndromes. Particular attention is paid to genetic testing, including when it is indicated, methods used and potential pitfalls. The role of the genetic counselor is also explored.

Pamela Sklar and colleagues report a genome-wide association study of bipolar disorder and identify variants in the genes encoding ankyrin-3 and the alpha-1C subunit of the L-type voltage-gated calcium channel as increasing risk.

A multi-ancestry genome-wide association study of prostate cancer performed in 156,319 cases and 788,443 controls identifies 187 novel risk variants associated with the disease. Genetic risk scores associated with overall risk, and risk of aggressive disease in men of African ancestry.

Positron emission tomography measurements of nutrient uptake in cells of the tumour microenvironment reveal cell-intrinsic partitioning in which glucose uptake is higher in myeloid cells, whereas glutamine is preferentially acquired by cancer cells.

170 million people worldwide are chronically infected with hepatitis C virus (HCV), which is the leading cause of cirrhosis in North America. Many patients are not cured by the current recommended treatment regime, with patients of European ancestry having a higher probability of being cured than those of African ancestry. Here, a genetic polymorphism near the IL28B gene is found to be associated with a better response to treatment; it occurs with higher frequency in European populations.

Worldwide, 170 million people are infected with the hepatitis C virus, which is a significant cause of liver-related illnesses and deaths. Standard treatment combines pegylated interferon alpha and ribavirin (RBV), but has some negative effects, notably RBV-induced haemolytic anaemia. Here, a genome-wide study shows that a deficiency in the enzyme inosine triphosphatase protects against haemolytic anaemia in patients receiving RBV.