Research articles

Genetic associations based on parental history of Alzheimer’s disease are shown to be impacted by uncorrected survival bias and nonrandom survey participation, underscoring the need for caution when interpreting results based on this study design.

High-quality assemblies of 15 diploid and 35 allotetraploid cotton accessions are analyzed in graph-based pan-genomes, providing insights into genome dynamics and regulatory control of fiber transcriptomes under varying ploidy and selection pressures.

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.

Analysis of pan-cancer clinical genomic sequencing finds that body mass index associates with driver mutations in certain cancer types, including most prominently lung adenocarcinoma. Obesity may thus influence tumor genetics.

Functional screens using mouse and human primary macrophages identify regulators of distinct inflammatory states, including a role for m6A mRNA modification in TNF production.

Genome-wide association analyses of intracranial and nine subcortical brain volumes in 74,898 participants of European ancestry identify 254 independent loci and yield polygenic scores accounting for brain variation across ancestries.

Chromosome-scale and haplotype-resolved assembly of Pinus densiflora sheds light on Pinus-specific genome enlargement. Comparison between haplotypes and resequencing of 30 wild accessions show allelic imbalance with roles in flowering regulation and stress resistance.

Base editing screens of 11 cancer genes identify four functional classes of variants that collectively underpin sensitivity and resistance to ten commonly used drugs in cancer cell lines.

Maize transcription factor TASSELSHEATH4 establishes the leaf versus meristem cell boundary and vegetative versus floral axillary meristem fates as part of a domestication gene network.

Genome-wide association analysis of gout and urate identifies 148 new loci, implicating biological pathways and prioritizing candidate genes involved in inflammatory processes.

A pan-cancer genomic analysis finds an increase of extrachromosomal DNA (ecDNA) in treated and metastatic tumors compared to primary, untreated samples, as well as ecDNA features enriched in advanced disease.

A new method called polymerase error rate sequencing (PER-seq) can measure the nucleotide misincorporation rate of DNA polymerases. DNA polymerase ε mutants produce an excess of CpG<TpG errors during DNA replication in a deamination-independent manner resembling the mutation spectrum in tumors.

Genome-wide analyses identify common variants associated with 11 distinct neuropathology endophenotypes, providing insights into the mechanisms underlying the genetic risk of Alzheimer’s disease and related dementias.

Rare variant analyses identify a new type 2 diabetes risk allele near the LEP gene, which encodes leptin, and other risk alleles of intermediate penetrance in genes previously implicated in monogenic forms of diabetes.

Analyses of height and body mass index in 119,000 sibling pairs show that linkage and genome-wide association signals colocalize. Further analyses suggest that family-based linkage signals are fully consistent with a highly polygenic architecture.

Analysis of exomes and transcriptomes from 100 African American patients with acute myeloid leukemia identifies ancestry-related variation in mutation profiles and survival. Refined risk classification suggests clinical relevance of these ancestry-associated differences.

Genome-wide association and fine-mapping analyses in approximately 260,000 Japanese individuals combined with a newly constructed Japanese-specific genotype reference panel identify hundreds of new loci and putative causal variants for 63 quantitative traits.

This study identifies context-only transcription factors (TFs), a TF class that enhances DNA accessibility initiated by cell type-specific TFs and establishes cooperative environments. Enhancers enriched with motifs of both TF classes show high coactivator binding, enhanced coordination and sensitivity to bromodomain inhibitors.

Genome-wide association analyses of prostate cancer in men from sub-Saharan Africa identify population-specific risk variants and regional differences in effect sizes. Founder effects contribute to continental differences in the genetic architecture of prostate cancer.

Major histocompatibility complex (MHC) loss of heterozygosity, allele-specific mutation and measurement of expression and repression (MHC Hammer) detects disruption to human leukocyte antigens due to mutations, loss of heterogeneity, altered gene expression or alternative splicing. Applied to lung and breast cancer datasets, the tool shows that these aberrations are common across cancer and can have clinical implications.