ArticleNature genetics2016
Recurring exon deletions in the HP (haptoglobin) gene contribute to lower blood cholesterol levels.
Article in Nature genetics, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 65 papers, 6 of them syntheses that pooled it.
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Who cites it
65 citing papers in PubMed, 6 syntheses or guidelines pooled it.
- A haptoglobin (HP) structural variant alters the effect of APOE alleles on Alzheimer's disease.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2023Pooled it
- Mendelian randomization and genetic colocalization infer the effects of the multi-tissue proteome on 211 complex disease-related phenotypes.Genome medicine · 2022Pooled it
- Genetic determinants of circulating haptoglobin concentration.Clinica chimica acta; international journal of clinical chemistry · 2019Pooled it
- Association of haptoglobin phenotype with incident acute myocardial infarction in Chinese patients with type 2 diabetes.Cardiovascular diabetology · 2019Pooled it
- Fifteen new risk loci for coronary artery disease highlight arterial-wall-specific mechanisms.Nature genetics · 2017Pooled it
- Haptoglobin Genotype and Outcome after Subarachnoid Haemorrhage: New Insights from a Meta-Analysis.Oxidative medicine and cellular longevity · 2017Pooled it
- Structural Variants in the Human Genome Associated With Gut Microbiome and Blood Metabolic Traits With Potential Causal Links.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Article
- Admixture-mapping analysis reveals genetic determinants of the human plasma proteome.HGG advances · 2026Observational
- Integrative Genetic, Proteogenomic, and Multi-omics Analyses Reveal Sex-Biased Causal Genes and Drug Targets in Alzheimer's Disease.medRxiv : the preprint server for health sciences · 2025Article
- Long-read genome sequencing and multi-omics in aging and neurodegeneration.medRxiv : the preprint server for health sciences · 2025Article
- Diversity and consequences of structural variation in the human genome.Nature reviews. Genetics · 2025Review
- Relationship between time-varying achieved HbABMJ open diabetes research & care · 2025Article
- Retrospective studies and quantitative proteomics reveal that abnormal expression of blood pressure, blood lipids, and coagulation related proteins is associated with hypospadias.Human genetics · 2024Article
- Identification and Diagnosis of Complete Haptoglobin Gene Deletion, One of the Genes Responsible for Adverse Posttransfusion Reactions.Biomedicines · 2024Review
- Haptoglobin polymorphism, vitamin E and mortality: the Ludwigshafen Risk and Cardiovascular Health Study.BMJ nutrition, prevention & health · 2024Article
- Haptoglobin Gene Polymorphism Is Associated With Lower Postoperative Cardiovascular Risk in Carotid Stenosis Patients.Journal of stroke · 2024Article
- Polymorphic short tandem repeats make widespread contributions to blood and serum traits.Cell genomics · 2023Article
- Radiogenomics: a key component of precision cancer medicine.British journal of cancer · 2023Review
- Article
5 more citing papers are in PubMed but not listed here.
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7 authors.
Funding
Abstract
One of the first protein polymorphisms identified in humans involves the abundant blood protein haptoglobin. Two exons of the HP gene (encoding haptoglobin) exhibit copy number variation that affects HP protein structure and multimerization. The evolutionary origins and medical relevance of this polymorphism have been uncertain. Here we show that this variation has likely arisen from many recurring deletions, more specifically, reversions of an ancient hominin-specific duplication of these exons. Although this polymorphism has been largely invisible to genome-wide genetic studies thus far, we describe a way to analyze it by imputation from SNP haplotypes and find among 22,288 individuals that these HP exonic deletions associate with reduced LDL and total cholesterol levels. We further show that these deletions, and a SNP that affects HP expression, appear to drive the strong association of cholesterol levels with SNPs near HP. Recurring exonic deletions in HP likely enhance human health by lowering cholesterol levels in the blood.
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