Protein truncating variantMitochondrial dysfunctionLiver-related biomarkersChronic liver diseaseGenetic susceptibilityMitochondrial (MT) dysfunction is a hallmark of liver diseases. However, the effects of functional variants such as protein truncating variants (PTVs) in MT-related genes on the risk of ...
Obesity is a major risk factor for many common diseases and has a substantial heritable component. To identify new genetic determinants, we performed exome-sequence analyses for adult body mass index (BMI) in up to 587,027 individuals. We identified rare loss-of-function variants in two genes ...
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 ...
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. ...
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...
stop-gained and frameshift variants that are within 50 kb of the end of the transcript will be flagged as ‘low confidence’. We extracted variants predicted as PTVs, flagged as ‘high confidence’ by LOFTEE and with minor allele frequency (MAF) <1% in UK Biobank participants of white ...
Protein-truncating variants (PTVs), also commonly referred to as loss-of-function variants4 as they often result in a non-functional or unstable gene product, are generally the strongest acting genetic variants in medical genetics and, as one functional copy of the gene is removed, may often ...
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 (...
(12) sequenced exons of CETP in 58,469 individuals from 12 case-control studies (18,817 CHD cases and 39,652 control subjects) to identify protein-truncating variants (PTVs). Individuals carrying 1 CETP PTV, of whom there were 60 in the study, had 22.6-mg/dl (0.59-mmol/l) higher ...
Exome sequence data from 60,706 individuals provide sufficient observations of rare protein truncating variants (PTVs) to make genome-wide estimates of selection against heterozygous loss of gene function. The cumulative frequency of rare deleterious PTVs is primarily determined by the balance between ...