ArticleGenome research2013
Identifying multiple causative genes at a single GWAS locus.
Article in Genome research, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 79 papers, 5 of them syntheses that pooled it.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
79 citing papers in PubMed, 5 syntheses or guidelines pooled it, 119 citations in OpenAlex.
- Genetic meta-analysis of diagnosed Alzheimer's disease identifies new risk loci and implicates Aβ, tau, immunity and lipid processing.Nature genetics · 2019Pooled it
- Multiancestry genome-wide association study of 520,000 subjects identifies 32 loci associated with stroke and stroke subtypes.Nature genetics · 2018Pooled it
- Integrative genomics identifies new genes associated with severe COPD and emphysema.Respiratory research · 2018Pooled it
- Rare Exome Sequence Variants in CLCN6 Reduce Blood Pressure Levels and Hypertension Risk.Circulation. Cardiovascular genetics · 2016Pooled it
- 2015 Guidelines for Establishing Genetically Modified Rat Models for Cardiovascular Research.Journal of cardiovascular translational research · 2015Guideline
- Locus-specific stratification and prioritization unveil genetic risk mechanism underlying complex diseases.Nature communications · 2026Article
- Early and late RNA eQTL are driven by different genetic mechanisms.Nature communications · 2026Article
- Cell-specific variant-to-gene mapping identifies conserved neural and glial regulators of sleep.bioRxiv : the preprint server for biology · 2026Article
- Assessing the readiness of Oxford Nanopore sequencing for clinical genomics applications.Genome research · 2026Article
- Rethinking GWAS: how lessons from genetic screens and artificial intelligence could reveal biological mechanisms.Bioinformatics (Oxford, England) · 2025Article
- MARSweb: a fully automated web service for set-based association testing.BMC genomics · 2025Article
- The effects of the atrial natriuretic peptide deficiency on renal cortical mitochondrial bioenergetics in the Dahl SS rat.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2024Article
- Tree-based QTL mapping with expected local genetic relatedness matrices.American journal of human genetics · 2023Article
- Genetic polymorphisms of purinergic P2YPurinergic signalling · 2023Article
- Assessing efficiency of fine-mapping obesity-associated variants through leveraging ancestry architecture and functional annotation using PAGE and UKBB cohorts.Human genetics · 2023Article
- Article
- Multiomics Data Analysis Identified CpG Sites That Mediate the Impact of Smoking on Cardiometabolic Traits.Epigenomes · 2023Article
- Tree-based QTL mapping with expected local genetic relatedness matrices.bioRxiv : the preprint server for biology · 2023Article
- A systems biology approach identifies the role of dysregulated PRDM6 in the development of hypertension.The Journal of clinical investigation · 2023Article
- Genetic Modifications to Alter Blood Pressure Level.Biomedicines · 2022Review
19 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
10 authors at 2 institutions in 1 country.
Funding
Abstract
Genome-wide association studies (GWAS) are useful for nominating candidate genes, but typically are unable to establish disease causality or differentiate between the effects of variants in linkage disequilibrium (LD). Additionally, some GWAS loci might contain multiple causative variants or genes that contribute to the overall disease susceptibility at a single locus. However, the majority of current GWAS lack the statistical power to test whether multiple causative genes underlie the same locus, prompting us to adopt an alternative approach to testing multiple GWAS genes empirically. We used gene targeting in a disease-susceptible rat model of genetic hypertension to test all six genes at the Agtrap-Plod1 locus (Agtrap, Mthfr, Clcn6, Nppa, Nppb, and Plod1) for blood pressure (BP) and renal phenotypes. This revealed that the majority of genes at this locus (five out of six) can impact hypertension by modifying BP and renal phenotypes. Mutations of Nppa, Plod1, and Mthfr increased disease susceptibility, whereas Agtrap and Clcn6 mutations decreased hypertension risk. Reanalysis of the human AGTRAP-PLOD1 locus also implied that disease-associated haplotype blocks with polygenic effects were not only possible, but rather were highly plausible. Combined, these data demonstrate for the first time that multiple modifiers of hypertension can cosegregate at a single GWAS locus.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.