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Jan 24, 2025 | 
digitalcommons.library.tmc.edu | YING WANG |Masahiro Kanai |Taotao Tan |Mireille Kamariza
Keywordsgenome-wide association studies, multi-ancestry, polygenic risk scores, genetic architectureAbstractPolygenic risk scores (PRSs) developed from multi-ancestry genome-wide association studies (GWASs), PRSmulti, hold promise for improving PRS accuracy and generalizability across populations.
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Sep 19, 2024 | 
biorxiv.org | Hilary Finucane |Jeremy Guez |Masahiro Kanai |Sophie Parsa
AbstractVariant scoring methods (VSMs) aid in the interpretation of coding mutations and their potential impact on health, but their evaluation in the context of human genetics applications remains inconsistent. Here, we describe GeneticsGym, a systematic approach to evaluating the real-world impact of VSMs on human genetic analysis across selection regimes.
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Sep 11, 2024 | 
biorxiv.org | Hannah Jacobs |Bram L. Gorissen |Masahiro Kanai |Jeremy Guez
AbstractMost mammalian genes undergo alternative splicing. The splicing of some exons has been acquired or lost in specific mammalian lineages, but differences in splicing within the human population are poorly characterized. Using GTEx tissue transcriptomes from 838 individuals, we identified 56,415 exons which are included in mRNAs in some individuals but entirely excluded from others, which we term 'naturally variable exons' (NVEs).
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Jul 23, 2024 | 
nature.com | Wei Gan |Robert Clarke |Masaru Koido |Masahiro Kanai |Yukinori Okada |Yoichiro Kamatani | +7 more
AbstractElevated blood pressure (BP) is major risk factor for cardiovascular diseases (CVD). Genome-wide association studies (GWAS) conducted predominantly in populations of European ancestry have identified >2,000 BP-associated loci, but other ancestries have been less well-studied. We conducted GWAS of systolic, diastolic, pulse, and mean arterial BP in 100,453 Chinese adults. We identified 128 non-overlapping loci associated with one or more BP traits, including 74 newly-reported associations.
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Jul 3, 2024 | 
nature.com | Caitlin Carey |Robbee Wedow |Duncan Palmer |Masahiro Kanai |Konrad J Karczewski |Samuel Bryant | +6 more
AbstractData within biobanks capture broad yet detailed indices of human variation, but biobank-wide insights can be difficult to extract due to complexity and scale. Here, using large-scale factor analysis, we distill hundreds of variables (diagnoses, assessments and survey items) into 35 latent constructs, using data from unrelated individuals with predominantly estimated European genetic ancestry in UK Biobank.
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Jun 3, 2024 | 
nature.com | Rahul Gupta |Masahiro Kanai |Timothy Durham |Anna V. Kotrys |Wei Zhou |Konrad J Karczewski | +1 more
Correction to: Nature https://doi.org/10.1038/s41586-023-06426-5Published online 16 August 2023When performing a genome-wide association study (GWAS), the choice of which allele (reference vs. alternate) is considered the “effect allele” is arbitrary. In our computations, we chose the reference allele. For a small subset of our results, the effect sizes were erroneously attributed to the alternate allele.
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May 16, 2024 | 
medrxiv.org | Wei Zhou |Anna SE Cuomo |Angli Xue |Masahiro Kanai
B.M.N. is a member of the scientific advisory board at Deep Genomics and Neumora. M.D. is a founder of Maze Therapeutics. W.Z. was supported by the National Human Genome Research Institute of the National Institutes of Health under award number K99/R00HG012222. A.C. was supported by an EMBO Long Term Postdoctoral Fellowship (EMBO ALTF 424-2022). B.M.N. is supported by the Novo Nordisk Foundation (NNF21SA0072102) and R01MH101244. BMN and GC are supported by R37MH107649.
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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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Mar 15, 2024 | 
medrxiv.org | Konrad J Karczewski |Rahul Gupta |Masahiro Kanai |Wenhan Lu
K.J.K. is a consultant for Tome Biosciences, AlloDx, and Vor Biosciences, and a member of the scientific advisory board of Nurture Genomics. M.J.D is a founder of Maze Therapeutics. B.M.N. is a member of the scientific advisory board at Deep Genomics and Neumora. This work was supported by the Novo Nordisk Foundation (NNF21SA0072102), NIH grants R37MH107649, R00MH117229, K01MH121659, F31HL167378, and F30AG074507, and BroadIgnite funding.
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Jan 15, 2024 | 
nature.com | Masahiro Kanai |Qingbo Wang |Jessica Alföldi |William Phu |Yossi Farjoun |Anne H. O’Donnell-Luria | +4 more
Correction to: Nature https://doi.org/10.1038/s41586-023-06045-0 Published online 6 December 2023In the version of this article initially published, data points did not appear in Supplementary Figs. 6–8, and are now included in the online version of the Supplementary Information. About this articleChen, S., Francioli, L.C., Goodrich, J.K. et al. Author Correction: A genomic mutational constraint map using variation in 76,156 human genomes. Nature (2024).
