First trial of 'base editing' in humans lowers cholesterol - but raises safety concerns.
Miryam Naddaf et al. Nature 2023 11
From the paper: "The first trial in humans of the precise gene-editing technique known as base editing has shown promising results for keeping cholesterol levels in check in patients with familial hypercholesterolemia. The approach injects into people a treatment called VERVE-101, which permanently deactivates a gene in the liver called PCSK9. That gene controls the level of low-density lipoprotein (LDL), or ‘bad’ cholesterol — a key contributor to heart disease. But the findings have also drawn criticism. Two serious adverse events in the trial, including a death, have raised safety concerns. "
The burden of splice-disrupting variants in inherited heart disease and unexplained sudden cardiac death
ES Singer et al, NPJ Genomic Medicine, October 11, 2023
From the abstract: "We performed burden testing of rare splice-disrupting variants in people with inherited heart disease and sudden unexplained death compared to 125,748 population controls. ClinGen definitively disease-associated inherited heart disease genes were amplified using RNA extracted from fresh blood, derived cardiomyocytes, and myectomy tissue. Variants were functionally assessed and classified for pathogenicity. We found 88 in silico-predicted splice-disrupting variants in 128 out of 1242 (10.3%) unrelated participants. "
A linear weighted combination of polygenic scores for a broad range of traits improves prediction of coronary heart disease.
Kristjan Norland et al. Eur J Hum Genet 2023 9
From the abstract: "Polygenic scores (PGS) for coronary heart disease (CHD) are constructed using GWAS summary statistics for CHD. However, pleiotropy is pervasive in biology and disease-associated variants often share etiologic pathways with multiple traits. Therefore, incorporating GWAS summary statistics of additional traits could improve the performance of PGS for CHD. "
Risk perception and intended behavior change after uninformative genetic results for adult-onset hereditary conditions in unselected patients.
Nandana D Rao et al. Eur J Hum Genet 2023 9
From the abstract: "Overall, 2761 people received uninformative results and 1352 (49%) completed survey items. Respondents averaged 41 years old, 62% were female, and 56% were Non-Hispanic Asian. Results from the FACToR instrument showed mean (SD) scores of 0.92 (1.34), 7.63 (3.95), 1.65 (2.23), and 0.77 (1.50) for negative emotions, positive emotions, uncertainty, and privacy concerns, respectively, suggesting minimal psychosocial harms from genetic screening. Overall, 12.2% and 9.6% of survey respondents believed that their risk of cancer or heart disease, respectively, had changed after receiving their uninformative genetic screening results. Further, 8.5% of respondents planned to make healthcare changes and 9.1% other behavior changes. "