Nature, Published online: 24 June 2025; doi:10.1038/d41586-025-01717-5
A gender gap in mathematical ability arises shortly after children begin school — irrespective of the type of school they attend and their socio-economic background.
Nature, Published online: 26 February 2025; doi:10.1038/s41586-025-08623-w
A rare variant burden analytical framework for Mendelian diseases was developed and applied to data from the 100,000 Genomes Project, identifying 69 probable new disease–gene associations.
Nat Comput Sci. 2025 Feb 7. doi: 10.1038/s43588-024-00764-8. Online ahead of print.
ABSTRACT
Large-scale whole-genome sequencing (WGS) studies have improved our understanding of the contributions of coding and noncoding rare variants to complex human traits. Leveraging association effect sizes across multiple traits in WGS rare variant association analysis can improve statistical power over single-trait analysis, and also detect pleiotropic genes and regions. Existing multi-trait methods have limited ability to perform rare variant analysis of large-scale WGS data. We propose MultiSTAAR, a statistical framework and computationally scalable analytical pipeline for functionally informed multi-trait rare variant analysis in large-scale WGS studies. MultiSTAAR accounts for relatedness, population structure and correlation among phenotypes by jointly analyzing multiple traits, and further empowers rare variant association analysis by incorporating multiple functional annotations. We applied MultiSTAAR to jointly analyze three lipid traits in 61,838 multi-ethnic samples from the Trans-Omics for Precision Medicine (TOPMed) Program. We discovered and replicated new associations with lipid traits missed by single-trait analysis.
PMID:39920506 | DOI:10.1038/s43588-024-00764-8
Am J Hum Genet. 2025 Jan 6:S0002-9297(24)00456-7. doi: 10.1016/j.ajhg.2024.12.014. Online ahead of print.
ABSTRACT
Mosaic loss of Y (mLOY) is the most common somatic chromosomal alteration detected in human blood. The presence of mLOY is associated with altered blood cell counts and increased risk of Alzheimer disease, solid tumors, and other age-related diseases. We sought to gain a better understanding of genetic drivers and associated phenotypes of mLOY through analyses of whole-genome sequencing (WGS) of a large set of genetically diverse males from the Trans-Omics for Precision Medicine (TOPMed) program. We show that haplotype-based calling methods can be used with WGS data to successfully identify mLOY events. This approach enabled us to identify differences in mLOY frequencies across populations defined by genetic similarity, revealing a higher frequency of mLOY in the European (EUR) ancestry group compared to other ancestries. We identify multiple loci associated with mLOY susceptibility and show that subsets of human hematopoietic stem cells are enriched for the activity of mLOY susceptibility variants. Finally, we found that certain alleles on chromosome Y are more likely to be lost than others in detectable mLOY clones.
PMID:39809269 | DOI:10.1016/j.ajhg.2024.12.014
Nature, Published online: 08 January 2025; doi:10.1038/s41586-024-08388-8
Results from a comprehensive evaluation of the function of BRCA2 variants, particularly variants of uncertain significance, provide a useful resource to improve the clinical management of individuals who carry such genetic variants.
Nature, Published online: 26 June 2024; doi:10.1038/s41586-024-07552-4
A bispecific non-coding RNA expressed by the IS110 family of mobile genetic elements forms the basis of a programmable genome-editing system that enables the insertion, excision or inversion of specific target DNA sequences.
Oncogene, Published online: 08 May 2024; doi:10.1038/s41388-024-03054-9
A prismatic view of the epigenetic-metabolic regulatory axis in breast cancer therapy resistance
Nature, Published online: 08 April 2024; doi:10.1038/s41586-024-07379-z
Tumor-selective activity of RAS-GTP inhibition in pancreatic cancer
Cell Death Discovery, Published online: 05 April 2024; doi:10.1038/s41420-024-01933-4
Potential role of lipophagy impairment for anticancer effects of glycolysis-suppressed pancreatic ductal adenocarcinoma cells
Nature, Published online: 27 March 2024; doi:10.1038/s41586-024-07239-w
We introduce multinucleic acid interaction mapping in single cells (MUSIC), for concurrent profiling of multiplex chromatin interactions, gene expression and RNA–chromatin associations within individual nuclei, as a tool for exploring chromatin architecture and transcription.
Nature, Published online: 13 March 2024; doi:10.1038/s41586-024-07177-7
We uncover key processes of the genomic evolution of small cell lung cancer under therapy, identify the common ancestor as the source of clonal diversity at relapse and show central genomic patterns associated with drug response.
Nature, Published online: 14 February 2024; doi:10.1038/s41586-024-07060-5
Circular RNAs are exported from the nucleus by Ran-GTP, exportin-2 and IGF2BP1 in a mechanism analogous to protein export rather than mRNA export.
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