Etiqueta: AmJHumGenet

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…

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…

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…

Our study identifies the first human knockouts of OLA1 presenting with a hypermobility-neurodevelopmental syndrome supported by functional data derived from patient cells and C. elegans models. The work highlights OLA1 as a key regulator of microtubule…

We identify bi-allelic BLOC1S1 variants in 11 individuals with severe neurodevelopmental disease, including leukodystrophy, epilepsy, spasticity, and optic atrophy. Functional analyses demonstrate impaired lysosomal transport, defective autophagy, and …

Genomic analyses of Omani blood donors reveal a high frequency of the FyES allele at the Duffy locus, accompanied by elevated African ancestry. These alleles were likely introduced via early African admixture and rose in frequency through positive sele…

Chaldebas et al. develop 5ULTRA, a computational method for prioritizing 5′ UTR variants that could alter protein translation. By integrating 17 features of 5′ UTR biology into a machine-learning model, 5ULTRA identifies and prioritizes pathogenic germ…

The eMERGE Network implemented genome-informed risk assessment integrating polygenic, monogenic, clinical, and family history data for 11 diseases, returning results to 23,840 participants. This large prospective study evaluates whether genomic risk di…

Standard eQTL mapping and GWAS interpretation assume that each variant acts on one gene. However, neighboring genes can exhibit “allelic proxitropy,” where regulatory effects are shared. To identify these effects, we map QTLs on expression principal co…

The eMERGE Network’s multisite study of nearly 24,000 adults and children demonstrates the feasibility of returning genome-informed risk assessments for 11 diseases. Integrating polygenic risk scores with traditional factors increases high-risk identif…