Categoría: The American Journal of Human Genetics

Logica estimates local cross-ancestry genetic correlation from genome-wide association study summary statistics via a bivariate linear mixed model that accounts for ancestry-specific linkage-disequilibrium structure. Across simulations and 13 traits fr…

Bi-allelic variants in RPS6KC1 cause a neurodevelopmental disorder with features overlapping with Coffin-Lowry syndrome. Functional studies reveal impaired ribosomal protein synthesis, disrupted lipid signaling, and reduced mTOR activity, highlighting …

(The American Journal of Human Genetics 110, 963–978; June 1, 2023)

Ploidy abnormalities affect over 1% of human embryos. Haploidy typically results from absent sperm DNA, while triploidy mainly arises from maternal meiosis II errors. Triploidy also shows a linear maternal age effect and can be characterized by genome-…

COAST-SS extends the coding-variant allelic series test to operate on summary statistics: per-variant effect sizes, standard errors, and local linkage disequilibrium (LD). COAST-SS controls the type I error, is robust to LD misspecification, and enable…

RNA sequencing has emerged as a powerful tool for Mendelian disorder diagnostics, but the optimized sequencing depth has not been determined. Using Ultra-high-depth RNA sequencing (up to 1 billion reads), we improved detection of low-abundance genes an…

COMPADRE improves pedigree reconstruction through a novel combination of genome-wide IBD-sharing estimates with shared IBD segment data. COMPADRE achieves higher accuracy in comparison to existing tools, especially in pedigrees with many ungenotyped in…

Beyond commonly screened disorders, genomic-first ascertainment of genetic disorders remains underexplored. We developed a scalable framework for 2,701 additional rare genetic disorders, identifying pathogenic variants in 3.2% of a healthcare-based coh…

Cleft palate probands are globally enriched for protein-altering de novo variants, and gene-specific enrichment was found for seven cleft-related genes. Differences in individuals with syndromic versus nonsyndromic cleft palate were observed, although …

Loss-of-function variants in EIF3A and EIF3B can lead to a variable multisystem congenital disorder, primarily involving cardiac anomalies, craniofacial differences, and mild neurodevelopmental features. These findings are supported by an international…