ArticleNature genetics2015
Analysis of loss-of-function variants and 20 risk factor phenotypes in 8,554 individuals identifies loci influencing chronic disease.
Article in Nature genetics, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers, 1 of them a synthesis that pooled it.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
39 citing papers in PubMed, 1 synthesis or guideline pooled it, 54 citations in OpenAlex.
- Very low-depth sequencing in a founder population identifies a cardioprotective APOC3 signal missed by genome-wide imputation.Human molecular genetics · 2016Pooled it
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- Thioredoxin Domain Containing 5 (TXNDC5): Friend or Foe?Current issues in molecular biology · 2024Review
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- The role and mechanism of TXNDC5 in disease progression.Frontiers in immunology · 2024Review
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- Exome sequence association study of levels and longitudinal change of cardiovascular risk factor phenotypes in European Americans and African Americans from the Atherosclerosis Risk in Communities Study.Genetic epidemiology · 2021Article
- Increased CHIP Prevalence Amongst People Living with HIV.medRxiv : the preprint server for health sciences · 2020Article
- The ChinaMAP analytics of deep whole genome sequences in 10,588 individuals.Cell research · 2020Article
- Applications of genome editing technology in the targeted therapy of human diseases: mechanisms, advances and prospects.Signal transduction and targeted therapy · 2020Review
- An adaptive test for meta-analysis of rare variant association studies.Genetic epidemiology · 2020Article
- Integrative analysis of loss-of-function variants in clinical and genomic data reveals novel genes associated with cardiovascular traits.BMC medical genomics · 2019Article
- Insights into genetics, human biology and disease gleaned from family based genomic studies.Genetics in medicine : official journal of the American College of Medical Genetics · 2019Review
- Gut microbiome in type 1 diabetes: A comprehensive review.Diabetes/metabolism research and reviews · 2018Review
- Calculating the statistical significance of rare variants causal for Mendelian and complex disorders.BMC medical genomics · 2018Article
- Article
- Are Nonsense Alleles of Drosophila melanogaster Genes under Any Selection?Genome biology and evolution · 2018Article
- TXNDC5 contributes to rheumatoid arthritis by down-regulating IGFBP1 expression.Clinical and experimental immunology · 2018Article
- Whole-exome sequencing of sickle cell disease patients with hyperhemolysis syndrome suggests a role for rare variation in disease predisposition.Transfusion · 2018Article
Corrections and comments
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Authors and funding
15 authors at 6 institutions in 2 countries.
Funding
Abstract
A typical human exome harbors dozens of loss-of-function (LOF) variants, which can lower disease risk factor levels and affect drug efficacy. We hypothesized that LOF variants are enriched in genes influencing risk factor levels and the onset of common chronic diseases, such as cardiovascular disease and diabetes. To test this hypothesis, we sequenced the exomes of 8,554 individuals and analyzed the effects of predicted LOF variants on 20 chronic disease risk factor phenotypes. Analysis of this sample as discovery and replication strata of equal size verified two relationships in well-studied genes (PCSK9 and APOC3) and identified eight new loci. Previously unknown relationships included elevated fasting glucose in carriers of heterozygous LOF variation in TXNDC5, which encodes a biomarker for type 1 diabetes progression, and apparent recessive effects of C1QTNF8 on serum magnesium levels. These data demonstrate the utility of functional-variant annotation within a large sample of deeply phenotyped individuals for gene discovery.
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