Categoría: The American Journal of Human Genetics
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Bi-allelic variants in the ribosomal protein RPS6KC1 cause a complex neurodevelopmental disorder
The American Journal of Human Genetics 112, 2643–2664; November 6, 2025
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Multi-ancestry transcriptome prediction with functionally informed variants in TOPMed MESA improves performance of transcriptome-wide association studies
We proposed methods leveraging functionally informed variants for multi-ancestry transcriptome prediction and demonstrated improvements on multi-ancestry TWAS performance. Our proposed omnibus approach, which aggregates TWAS results, further improves T…
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Associations of genetic variants with gene expression factors reveal biological pathways underlying complex traits
GWASs have identified thousands of trait-associated variants, yet their downstream mechanisms remain unclear. By linking variants to pathway-level expression factors and developing the effect consistency test, we uncover biological pathways mediating i…
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This month in The Journal
Polygenic risk scores (PRSs) are promising tools that have the potential to help translate findings from genetic association studies into clinically meaningful health insights. As work on PRSs has increased, it has become clear that the accuracy of the…
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Implications of the FDA’s new plausible mechanism framework for the development of a personalized in vivo prime editing platform
The authors report initial proof-of-concept studies supporting a customizable prime editing platform geared to the treatment of 7 urea cycle disorders and other liver-centered disorders, as well as the outcome of a formal meeting with the FDA to discus…
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Implications of the FDA’s new plausible mechanism framework for the development of a personalized in vivo prime editing platform
The authors report initial proof-of-concept studies supporting a customizable prime editing platform geared to the treatment of 7 urea cycle disorders and other liver-centered disorders, as well as the outcome of a formal meeting with the FDA to discus…
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Implications of the FDA’s new plausible mechanism framework for the development of a personalized in vivo prime editing platform
The authors report initial proof-of-concept studies supporting a customizable prime editing platform geared to the treatment of 7 urea cycle disorders and other liver-centered disorders, as well as the outcome of a formal meeting with the FDA to discus…
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Bi-allelic variants in NDUFA5 cause a mitochondriopathy with complex I deficiency
We identify bi-allelic NDUFA5 variants in four individuals from three families with mitochondrial complex I deficiency. Genomic, transcriptomic, proteomic, and biochemical studies across patient tissues, complemented by a zebrafish model, characterize …
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Ultra-rare functional variants reveal early-onset breast cancer risk genes and pathways in the UK Biobank and All of Us Research Program
EA-Pathways, a control-free ultra-rare variant association method, recovers breast cancer risk pathways and genes from the germlines of affected women in the UK Biobank. A portion of these pathways is associated with earlier disease, and this extends t…
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Ultra-rare functional variants reveal early-onset breast cancer risk genes and pathways in the UK Biobank and All of Us Research Program
EA-Pathways, a control-free ultra-rare variant association method, recovers breast cancer risk pathways and genes from the germlines of affected women in the UK Biobank. A portion of these pathways is associated with earlier disease, and this extends t…