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Nov 11, 2024 | 
nature.com | Kenichi Yamamoto |Shinichi Namba |Kyuto Sonehara |Ken Suzuki |Saori Sakaue |Koichi Matsuda | +2 more
AbstractThe tripartite ancestral structure is a recently proposed model for the genetic origin of modern Japanese, comprising indigenous Jomon hunter-gatherers and two additional continental ancestors from Northeast Asia and East Asia. To investigate the impact of the tripartite structure on genetic and phenotypic variation today, we conducted biobank-scale analyses by merging Biobank Japan (BBJ; n = 171,287) with ancient Japanese and Eurasian genomes (n = 22).
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Sep 27, 2024 | 
nature.com | Qingbo Wang |Ho Namkoong |Ryunosuke Saiki |Kyuto Sonehara |Shuhei Azekawa |Yugo Takahashi | +12 more
Correction to: Nature Genetics https://doi.org/10.1038/s41588-024-01896-3, published online 24 September 2024. In the version of the article initially published, there was an error in the x-axis label of Fig. 1a, where in the text now reading “pQTL –log10(P) ≥ x” it originally read “… ≤ x.” In the keys to both graphs in Fig. 7b, the blue dot was listed as “β > 0” and has now been amended to “β < 0.” The symbols are corrected in the HTML and PDF versions of the article.
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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.
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Sep 24, 2024 | 
nature.com | Qingbo Wang |Ho Namkoong |Ryunosuke Saiki |Kyuto Sonehara |Shuhei Azekawa |Saori Sakaue | +12 more
AbstractStudying the genetic regulation of protein expression (through protein quantitative trait loci (pQTLs)) offers a deeper understanding of regulatory variants uncharacterized by mRNA expression regulation (expression QTLs (eQTLs)) studies. Here we report cis-eQTL and cis-pQTL statistical fine-mapping from 1,405 genotyped samples with blood mRNA and 2,932 plasma samples of protein expression, as part of the Japan COVID-19 Task Force (JCTF).
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Jul 30, 2024 | 
nature.com | Joshua Chiou |Saori Sakaue |Stephen Christensen |Soumya Raychaudhuri
AbstractGenetic variation in the human leukocyte antigen (HLA) loci is associated with risk of immune-mediated diseases, but the molecular effects of HLA polymorphism are unclear. Here we examined the effects of HLA genetic variation on the expression of 2940 plasma proteins across 45,330 Europeans in the UK Biobank, with replication analyses across multiple ancestry groups.
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Jun 11, 2024 | 
nature.com | Garrett S. Dunlap |Nida Meednu |Ruoqiao Wang |fan zhang |Anna Jonsson |Kevin H-C Wei | +11 more
AbstractRheumatoid arthritis (RA) is an autoimmune disease involving antigen-specific T and B cells. Here, we perform single-cell RNA and repertoire sequencing on paired synovial tissue and blood samples from 12 seropositive RA patients. We identify clonally expanded CD4 + T cells, including CCL5+ cells and T peripheral helper (Tph) cells, which show a prominent transcriptomic signature of recent activation and effector function.
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May 30, 2024 | 
nature.com | Kathryn Weinand |Saori Sakaue |Aparna Nathan |Anna Jonsson |fan zhang |Majd Al Suqri | +5 more
AbstractSynovial tissue inflammation is a hallmark of rheumatoid arthritis (RA). Recent work has identified prominent pathogenic cell states in inflamed RA synovial tissue, such as T peripheral helper cells; however, the epigenetic regulation of these states has yet to be defined. Here, we examine genome-wide open chromatin at single-cell resolution in 30 synovial tissue samples, including 12 samples with transcriptional data in multimodal experiments.
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May 30, 2024 | 
nature.com | Saori Sakaue
Genome-wide association studies (GWAS) have mapped hundreds of thousands of genomic locations that underlie disease susceptibility. However, only rarely is it possible to pinpoint causal variants or target genes from GWAS signals. More than 90% of loci act through non-coding, regulatory mechanisms, and predicting variant effects on gene expression has been extremely challenging.
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Apr 9, 2024 | 
nature.com | Saori Sakaue |Kushal Dey |Karthik A. Jagadeesh |Masahiro Kanai |Michael Brenner |Alkes L Price | +1 more
AbstractTranslating genome-wide association study (GWAS) loci into causal variants and genes requires accurate cell-type-specific enhancer–gene maps from disease-relevant tissues. Building enhancer–gene maps is essential but challenging with current experimental methods in primary human tissues.
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Jan 4, 2024 | 
nature.com | Xiangrui Meng |Daniel F Levey |Dora Koller |Mark Adams |Miguel E. Rentería |Dan Stein | +42 more
AbstractMost genome-wide association studies (GWAS) of major depression (MD) have been conducted in samples of European ancestry. Here we report a multi-ancestry GWAS of MD, adding data from 21 cohorts with 88,316 MD cases and 902,757 controls to previously reported data. This analysis used a range of measures to define MD and included samples of African (36% of effective sample size), East Asian (26%) and South Asian (6%) ancestry and Hispanic/Latin American participants (32%).
