Po-Ru Loh

Sep 26, 2024 | nature.com | Saori Sakaue |Aparna Nathan |Joseph Powell |Po-Ru Loh

AbstractDisease risk alleles influence the composition of cells present in the body, but modeling genetic effects on the cell states revealed by single-cell profiling is difficult because variant-associated states may reflect diverse combinations of the profiled cell features that are challenging to predefine. We introduce Genotype–Neighborhood Associations (GeNA), a statistical tool to identify cell-state abundance quantitative trait loci (csaQTLs) in high-dimensional single-cell datasets.

Jun 12, 2024 | nature.com | Aoxing Liu |Giulio Genovese |Yajie Zhao |Matti Pirinen |Xiaoxi Liu |Bryan R. Gorman | +15 more

AbstractMosaic loss of the X chromosome (mLOX) is the most common clonal somatic alteration in leukocytes of female individuals1,2, but little is known about its genetic determinants or phenotypic consequences. Here, to address this, we used data from 883,574 female participants across 8 biobanks; 12% of participants exhibited detectable mLOX in approximately 2% of leukocytes. Female participants with mLOX had an increased risk of myeloid and lymphoid leukaemias.

Oct 30, 2023 | nature.com | Teng Gao |Maria Eleni Kastriti |Po-Ru Loh |Peter J. Park

AbstractGenetic mutations accumulate in an organism’s body throughout its lifetime. While somatic single-nucleotide variants have been well characterized in the human body, the patterns and consequences of large chromosomal alterations in normal tissues remain largely unknown. Here, we present a pan-tissue survey of mosaic chromosomal alterations (mCAs) in 948 healthy individuals from the Genotype-Tissue Expression project, augmenting RNA-based allelic imbalance estimation with haplotype phasing.