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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.
Fine-mapping and functional studies highlight potential causal risk variants for rheumatoid arthritis and type 1 diabetes, including missense variants at DNASE1L3, PTPN22, SH2B3, and TYK2, and noncoding variants at MEG3, CD28–CTLA4, and IL2RA.
SEEKR is a method that deconstructs linear sequence relationships between lncRNAs and evaluates similarity on the basis of abundance of short motifs called k-mers. LncRNAs of related function often have similar k-mer profiles despite lacking linear homology.
De novo mutations in MSL3 cause an X-linked syndrome affecting both males and females. MSL3 mutations reduce H4K16ac levels and lead to misregulation of cellular pathways involved in morphogenesis, cellular shape, and cell migration.
Large-scale loss-of-function screens and TP53 saturation mutagenesis screens in human cancer cell lines suggest that mutational processes combine with phenotypic selection to shape the landscape of somatic mutations at the TP53 locus.
The authors present an integrative framework for identifying structural variants (SVs) in cancer that applies optical mapping, Hi-C, and whole-genome sequencing. They find SVs affecting distal regulatory sequences, DNA replication, and three-dimensional chromatin structure.
Signed linkage disequilibrium profile regression is a new method for detecting directional effects of genomic annotations on disease risk. The results implicate new causal disease genes and can suggest mechanisms underlying the effects of causal genes on disease.
Genome-wide analyses identify 42 risk loci for diverticular disease, 39 of which are new. Genes in associated regions are enriched for expression in connective tissue cell types and are coexpressed with genes involved in vascular and mesenchymal biology.
A new study uncovers novel copy number signatures in ovarian cancer genomes. This work sheds light on mutational processes driving ovarian cancer, reveals the distribution of copy number features across the patient population and identifies new genomic properties related to treatment response.
Precision genomic medicine is now technically feasible. Just as global positioning systems revolutionized the logistics of travel, so genome-wide polygenic risk scores (GPSs) now have the potential to inform our trajectories of health and to serve in the prevention and mitigation of many common and complex diseases. We welcome research into the implementation of—and equity of access to—genetic predictors and their integration into clinical and evidence-based medical practice.
Two new studies show that a plant-specific complex composed of EBS, or its homolog SHL, and EMF1 acts as a chromatin reader within the Polycomb pathway and effects gene repression. Two domains of EBS and SHL bind distinct chromatin modifications that are associated with active and repressed chromatin.
Individual genome-wide polygenic risk scores (GPSs) for assessing disease susceptibility have been shown to yield both reliable and clinically meaningful results. However, certain impediments and outdated ways of thinking about health maintenance must be overcome before GPSs are adopted in routine care streams.
This proposal calls for the initiation of national population-screening programs to identify carriers of cancer gene mutations for long-term, large-scale analysis of longitudinal clinical data to aid in prevention and early detection of disease.
Analysis of sequencing data from 249 cancer patients with clinically annotated outcomes to immune checkpoint therapy identifies correlates of treatment response. The results highlight complexity in identifying events that generate an immunoresponsive tumor environment.
Analysis of GTEx, cancer and autism data sets shows that cis-regulatory variation can modify the penetrance of coding variants. Deleterious coding variants on regulatory haplotypes resulting in high expression are enriched in disease cohorts and selected against in general populations.
This study identifies a set of critical dependency genes in MYCN-amplified neuroblastoma that make up the oncogenic transcriptional regulatory circuitry underlying cell state and tumor survival.