Etiqueta: AmJHumGenet

Fatty acids function as energy sources, structural components, and signaling mediators. To investigate their genetic regulation across tissues, we profiled fatty acid content in adipose tissue biopsies from 569 twins. We identify heritable fatty acids …

Through systematic evaluation of 290 individuals with ACTB or ACTG1 variants, we delineate eight non-muscle actinopathies with distinct clinical profiles. Clear genotype-phenotype correlations, characteristic facial gestalts, and organ involvement patt…

Loss-of-function variants in NPR2 are associated with short-stature disorders. A high-throughput GFP reporter assay classified functional activity of NPR2 missense variants, revealing a near-linear association between activity level and standing height…

We often describe the functional effects of genetic variants using terms such as “loss of function” or “gain of function.” These terms have an origin in Muller’s morphs, a classification system published almost a hundred years ago. At that time, the st…

LiMA and its random-effect variant I-LiMA infer molecular mediation in a Mendelian randomization framework using summary statistics. Jointly modeling direct and mediated effects while accounting for measurement error, they reduce weak-instrument bias a…

When I was young, my parents gave me a book by Paula Taylor called The Kids’ Whole Future Catalog: A Book About Your Future, with the “Your” underlined for emphasis.1 In its pages were fanciful descriptions of things that even now are recognizable as c…

De novo variants in KDM2A cause a syndromic neurodevelopmental disorder with a phenotypic spectrum of mild to severe developmental delay, feeding difficulties, short stature, microcephaly, and recurrent facial features. Functional studies in human cell…

MSH3 modifies both age of onset and the somatic instability of the X-linked dystonia parkinsonism hexanucleotide repeat. This highlights a critical role of somatic instability in driving disease, highlights MSH3 as a human-validated therapeutic target,…

GPSEA is a software tool that uses the GA4GH Phenopacket Schema to streamline discovery of genotype-phenotype correlations (GPCs) in Mendelian diseases. Analyzing data from 85 cohorts of previously published individuals, it identified 253 significant G…

Genetic risk is estimated in two ways: by looking at either a person’s genome or their family tree. Krebs et al. show that combining these approaches significantly improves predictions of psychiatric disorders. To guide interpretation, they offer quant…