Categoría: The American Journal of Human Genetics

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…

The current biotechnology industry is characterized by intense competition. Although this competition can drive innovation and increased investment, too much competition can prevent collaboration and potentially foster a culture in which data and metho…

Ancient DNA enables direct observation of alleles through time. However, the utility of available ancient human genotypes is limited by a focus on ∼1.23 million variants. Here, we address this limitation by generating a catalog of ancient genotyped pro…

This study reveals that dominant and recessive variants in ATOH1, a key transcription factor for hindbrain and mechanosensory development, cause distinct syndromes. Dominant C-terminal truncating variants induce a recognizable hindbrain malformation, m…

Morsy, Kim, and Jang et al. identify homozygous loss-of-function variants in MDGA2 in individuals with autosomal-recessive developmental and epileptic encephalopathy (DEE). Functional data demonstrate impaired MDGA2 trafficking and disrupted MDGA2-depe…

Here, we offer a perspective on the US legal landscape regarding the promotion of competition, with specific attention given to the human genetics and genomics industry. We highlight current policy on mergers, non-competition agreements, and exclusive …

We show that transcriptome-wide association studies (TWAS) and related methods (xWAS) using genetic predictors suffer from inflated false-positive rates for highly polygenic complex traits, increasing linearly with sample size and heritability. We prop…

This manuscript firmly establishes ASTN1 as a recessive neurodevelopmental disease gene, broadens the phenotypic spectrum of ASTN1-related neurodevelopmental disorders, provides further evidence for the contribution of splicing aberration to neurodevel…