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Open AccessPlasma proteomic associations with genetics and health in the UK Biobank
The Pharma Proteomics Project is a precompetitive biopharmaceutical consortium characterizing the plasma proteomic profiles of 54,219 UK Biobank participants. Here we provide a detailed summary of this initiat...
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Article
Using human genetics to improve safety assessment of therapeutics
Human genetics research has discovered thousands of proteins associated with complex and rare diseases. Genome-wide association studies (GWAS) and studies of Mendelian disease have resulted in an increased und...
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Open AccessRare loss of function variants in the hepatokine gene INHBE protect from abdominal obesity
Identifying genetic variants associated with lower waist-to-hip ratio can reveal new therapeutic targets for abdominal obesity. We use exome sequences from 362,679 individuals to identify genes associated with...
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Open AccessGene-level analysis of rare variants in 379,066 whole exome sequences identifies an association of GIGYF1 loss of function with type 2 diabetes
Sequencing of large cohorts offers an unprecedented opportunity to identify rare genetic variants and to find novel contributors to human disease. We used gene-based collapsing tests to identify genes associat...
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Open AccessA proteomic platform to identify off-target proteins associated with therapeutic modalities that induce protein degradation or gene silencing
Novel modalities such as PROTAC and RNAi have the ability to inadvertently alter the abundance of endogenous proteins. Currently available in vitro secondary pharmacology assays, which evaluate off-target bind...
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Open AccessGWAS of serum ALT and AST reveals an association of SLC30A10 Thr95Ile with hypermanganesemia symptoms
Understanding mechanisms of hepatocellular damage may lead to new treatments for liver disease, and genome-wide association studies (GWAS) of alanine aminotransferase (ALT) and aspartate aminotransferase (AST)...
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Open AccessAssociation of the transthyretin variant V122I with polyneuropathy among individuals of African ancestry
Hereditary transthyretin-mediated (hATTR) amyloidosis is an underdiagnosed, progressively debilitating disease caused by mutations in the transthyretin (TTR) gene. V122I, a common pathogenic TTR mutation, is foun...
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Open AccessAuthor Correction: Phenotypes associated with genes encoding drug targets are predictive of clinical trial side effects
In the original version of this article, there were errors in the labelling of the colours in the key of Figure 2, whereby the labeling of the third and fourth of the four colours was reversed. This has been c...
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Open AccessPhenotypes associated with genes encoding drug targets are predictive of clinical trial side effects
Only a small fraction of early drug programs progress to the market, due to safety and efficacy failures, despite extensive efforts to predict safety. Characterizing the effect of natural variation in the gene...
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Open AccessComment on “Using Human ‘Experiments of Nature’ to Predict Drug Safety Issues: An Example with PCSK9 Inhibitors”
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Open AccessA rare missense variant in NR1H4 associates with lower cholesterol levels
Searching for novel sequence variants associated with cholesterol levels is of particular interest due to the causative role of non-HDL cholesterol levels in cardiovascular disease. Through whole-genome sequen...
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Open AccessWhole genome characterization of sequence diversity of 15,220 Icelanders
Understanding of sequence diversity is the cornerstone of analysis of genetic disorders, population genetics, and evolutionary biology. Here, we present an update of our sequencing set to 15,220 Icelanders who...
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Parental influence on human germline de novo mutations in 1,548 trios from Iceland
Whole-genome sequencing data of 14,688 Icelanders, including 1,548 parent–offspring trios, show how the age and sex of parents affect the rate and spectrum of de novo mutations.
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Open AccessEpigenetic and genetic components of height regulation
Adult height is a highly heritable trait. Here we identified 31.6 million sequence variants by whole-genome sequencing of 8,453 Icelanders and tested them for association with adult height by imputing them int...
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Fine map** of type 1 diabetes susceptibility loci and evidence for colocalization of causal variants with lymphoid gene enhancers
Stephen Rich and colleagues report the discovery and fine map** of type 1 diabetes susceptibility loci using the Immunochip. They also perform comparative analyses with 15 other immune disorders and find evi...
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Open AccessIntegrative analysis of 111 reference human epigenomes
The reference human genome sequence set the stage for studies of genetic variation and its association with human disease, but epigenomic studies lack a similar reference. To address this need, the NIH Roadmap...
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Open AccessCharacterizing a collective and dynamic component of chromatin immunoprecipitation enrichment profiles in yeast
Recent chromatin immunoprecipitation (ChIP) experiments in fly, mouse, and human have revealed the existence of high-occupancy target (HOT) regions or “hotspots” that show enrichment across many assayed DNA-bi...
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Interpreting noncoding genetic variation in complex traits and human disease
Association studies provide genome-wide information about the genetic basis of complex disease, but medical research has focused primarily on protein-coding variants, owing to the difficulty of interpreting no...
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Open AccessA high-resolution map of human evolutionary constraint using 29 mammals
The comparison of related genomes has emerged as a powerful lens for genome interpretation. Here we report the sequencing and comparative analysis of 29 eutherian genomes. We confirm that at least 5.5% of the ...
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Map** and analysis of chromatin state dynamics in nine human cell types
Chromatin profiling has emerged as a powerful means of genome annotation and detection of regulatory activity. The approach is especially well suited to the characterization of non-coding portions of the genom...
