706 individuals4to make genome-wide estimates of selection against heterozygous loss of gene function. 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 ...
The present study sought to determine whether protein-truncating variants (PTVs) in PIEZO1 and CASZ1 genes, previously shown to be associated with varicose veins, were associated with an altered risk of varicose veins.#An exome sequence database of 131,918 participants from the Geisinger MyCode...
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 ...
SCZ is a severe, chronic psychiatric illness associated with lifelong progression and early mortality2,3,4. The genetic architecture of SCZ includes clear contributions from common single-nucleotide polymorphisms (SNPs)5, large copy number variants (CNVs)6and rare PTVs1,7,8,9,10,11,12,13,14....
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. ...
DeBoever, C. et al. Medical relevance of protein-truncating variants across 337,205 individuals in the UK Biobank study.Nat. Commun.9 ArticlePubMedPubMed CentralGoogle Scholar Narasimhan, V. M. et al. Health and population effects of rare gene knockouts in adult humans with related parents.Sc...
The evidence, however, largely comes from protein-truncating variants (PTVs) as opposed to de novo missense (dnMis) variants. These results are intuitive; PTVs, on average, should be more damaging. Yet, dnMis variants are more common. Within the 6430 ASD cases recently sequenced by the ...
Figure 5: Protein-truncating variation in ExAC. a, The average ExAC individual has 85 heterozygous and 35 homozygous protein-truncating variants (PTVs), of which 18 and 0.19 are rare (<1% allele frequency), respectively. Error bars represent standard deviation.b, Breakdown of PTVs per individua...
Two HCN1 interactor genes, HCN4 and AKAP11, are also enriched for schizophrenia-associated protein-truncating variants (PTVs) in SCHEMA (FDR = 4.2e-3 and 1.3e-2, respectively). In a meta-analysis of schizophrenia and bipolar disorder cases,48AKAP11 further emerged as an exome-wide ...
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 (...