Etiqueta: AmJHumGenet

Bi-allelic ultra-rare variants in FSD1L are identified as a cause of retinitis pigmentosa. One variant identified disrupts the splicing of a retina-enriched isoform. FSD1L localizes to the photoreceptor axoneme, implicating disruption of intracellular …

This study associates bi-allelic variants in FSD1L with a neurodevelopmental disorder closely resembling L1 syndrome, mainly characterized by hydrocephalus and corpus callosum defects. Functional experiments demonstrate that FSD1L encodes a microtubule…

We developed an automated, reproducible, and scalable workflow to perform scans for disproportionate identity-by-descent sharing between cases and controls, determining well-controlled significance levels by modeling correlations along the genome. When…

Two different 4-base-pair deletions in SMN1 that cause a similar frameshift led to false-positive SMA newborn screening results. Integrating genomic, functional, and population data clarified diagnosis, preventing unnecessary treatment, and demonstrate…

Rare mutations in PTEN, DISP1, SCUBE2, and FA2H were associated with changes in brain volume. Mutations in these genes have been linked with severe brain disorders. These findings suggest that these genes are relevant for neurodevelopment and that less…

(The American Journal of Human Genetics 112, 2625–2642; November 6, 2025)

To inform vascular disease processes attributable to alternative splicing, we modeled inflammation in endothelial cell lines. We found that alternative promoters were key regulators of transcript diversity, especially for metabolic genes. Using sQTL ma…

This investigation demonstrates the validity and high predictive ability of a prostate cancer polygenic risk score (PRS) across populations in the All of Us Research Program. It further demonstrates that PRS performance varies by certain demographic-, …

We performed chromatin accessibility quantitative trait locus (caQTL) mapping in 175 healthy human liver samples and identified 14,076 caQTLs. These data, along with other regulatory mechanism datasets, were integrated with liver-relevant genome-wide a…

Mendelian randomization (MR) is widely used to identify causality between human traits; however, it suffers from high error rates. Van der Graaf et al. benchmark MR using human metabolic networks to understand MR’s failure modes. Extensive biological f…