蛋白截断变异(protein-truncating variant,PTV)通过引入终止密码子,移码突变或剪接位点,破坏蛋白编码基因[1]。蛋白截断变异的研究对于人类进化(human evolution),基因功能(gene function),疾病相关变异(disease-related variants)和疾病患者变异的临床解读(Clinical interpretation of variants in patients with disease)有着重...
We applied MAF filters to target rare variants: MAF < 0.001 in gnomAD (overall and every population except OTH) and leave-one-out MAF < 0.001 among our combined case and control test cohort. For variants to qualify, they had to also meet the following quality control filters: minimum ...
Furthermore,BSNprotein-truncating variants (PTVs) magnified the influence of common genetic variants associated with BMI, with a common variant polygenic score exhibiting an effect twice as large inBSNPTV carriers than in noncarriers. Finally, we explored the plasma proteomic signatures ofBSNPTV ...
Protein-truncating variants can have profound effects on gene function and are critical for clinical genome interpretation and generating therapeutic hypotheses, but their relevance to medical phenotypes has not been systematically assessed. Here, we characterize the effect of 18,228 protein-truncating ...
A meta-analysis was then performed on protein-truncating variants (PTVs) identified in the studies for an association with breast cancer risk. A total of 10,209 publications were identified, of which 64 studies comprising a total of 25,418 cases and 52,322 controls in the 6 interrogated ...
555 controls of diverse ancestries. Replicating earlier work, we found that cases carried a significantly higher burden of rare protein-truncating variants (PTVs) among evolutionarily constrained genes (odds ratio = 1.48;P = 5.4 × 10−6). In meta-analyses with existing datasets...
Using this distribution of selection coefficients for heterozygous protein-truncating variants (PTVs), we provide corresponding Bayesian estimates for individual genes. We find that genes under the strongest selection are enriched in embryonic lethal mouse knockouts, Mendelian disease-associated genes, and ...
Genetic predisposition has been shown to contribute substantially to the age at which we die. Genome-wide association studies (GWASs) have linked more than 20 loci to phenotypes related to human lifespan1. However, little is known about how lifespan is i
and thesede novovariants do not contribute to neurodevelopmental risk. We further used a loss-of-function (LoF)-intolerance metric, pLI, to identify a subset of LoF-intolerant genes containing the observed signal of associatedde novoprotein-truncating variants (PTVs) in neurodevelopmental disorders. ...
Therefore, using whole-exome and whole-genome sequencing (WES and WGS, respectively), we aimed to identify novel PAVs and protein-truncating variants (PTVs, as putative loss-of-function variants) affecting serum lipid and lipoprotein measurements, complemented with serum nuclear magnetic resonance (...