ArticleAmerican journal of hematology2010
Genetic modifiers of the severity of sickle cell anemia identified through a genome-wide association study.
Article in American journal of hematology, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 46 papers, 2 of them syntheses that pooled it.
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Who cites it
46 citing papers in PubMed, 2 syntheses or guidelines pooled it, 101 citations in OpenAlex.
- Genetic Variation and Sickle Cell Disease Severity: A Systematic Review and Meta-Analysis.JAMA network open · 2023Pooled it
- Genetic determinants of lipid traits in diverse populations from the population architecture using genomics and epidemiology (PAGE) study.PLoS genetics · 2011Pooled it
- Patient reports of health outcome for adults living with sickle cell disease: development and testing of the ASCQ-Me item banks.Health and quality of life outcomes · 2014Trial
- Identification of Clinical Sub-Phenotypes of Sickle Cell Disease Using Latent Class Analysis.American journal of hematology · 2026Article
- Weather-Related Exposures and Emergency Department Visits for Pediatric Sickle Cell Complications.Pediatric emergency care · 2026Article
- Catechol-O-methyltransferase gene (COMT) is associated with neurocognitive functioning in patients with sickle cell disease.Current research in translational medicine · 2024Article
- Infrastructure for bioinformatics applications in Tanzania: Lessons from the Sickle Cell Programme.PLoS computational biology · 2023Article
- Is Severity Score Associated With Indication for Hematopoietic Stem Cell Transplantation in Individuals With Sickle Cell Anemia?Transplantation and cellular therapy · 2022Observational
- Fetal hemoglobin modulates neurocognitive performance in sickle cell anemiaCurrent research in translational medicine · 2022Article
- Computational Genomics in the Era of Precision Medicine: Applications to Variant Analysis and Gene Therapy.Journal of personalized medicine · 2022Review
- Bench Research Informed by GWAS Results.Cells · 2021Review
- Association of KLOTHO polymorphisms with clinical complications of sickle cell anemia.Annals of hematology · 2021Article
- The Genetic and Clinical Significance of Fetal Hemoglobin Expression in Sickle Cell Disease.Medical principles and practice : international journal of the Kuwait University, Health Science Centre · 2021Review
- Influence of β-Globin Haplotypes on Oxidative Stress, Antioxidant Capacity and Inflammation in Sickle Cell Patients of Chhattisgarh.Indian journal of clinical biochemistry : IJCB · 2019Article
- Development and evaluation of a transfusion medicine genome wide genotyping array.Transfusion · 2019Article
- Single tube allele specific PCR: a low cost technique for molecular screening of sickle cell anaemia in Nigeria.African health sciences · 2018Article
- Biomarker signatures of sickle cell disease severity.Blood cells, molecules & diseases · 2018Article
- Article
- Association between sickle cell anemia and alpha thalassemia reveals a high prevalence of the αJournal of clinical laboratory analysis · 2018Article
- Sensitivity of alternative measures of functioning and wellbeing for adults with sickle cell disease: comparison of PROMIS® to ASCQ-Me℠.Health and quality of life outcomes · 2017Article
Corrections and comments
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Authors and funding
13 authors at 4 institutions in 1 country.
Funding
Abstract
We conducted a genome-wide association study (GWAS) to discover single nucleotide polymorphisms (SNPs) associated with the severity of sickle cell anemia in 1,265 patients with either "severe" or "mild" disease based on a network model of disease severity. We analyzed data using single SNP analysis and a novel SNP set enrichment analysis (SSEA) developed to discover clusters of associated SNPs. Single SNP analysis discovered 40 SNPs that were strongly associated with sickle cell severity (odds for association >1,000); of the 32 that we could analyze in an independent set of 163 patients, five replicated, eight showed consistent effects although failed to reach statistical significance, whereas 19 did not show any convincing association. Among the replicated associations are SNPs in KCNK6 a K(+) channel gene. SSEA identified 27 genes with a strong enrichment of significant SNPs (P < 10(-6)); 20 were replicated with varying degrees of confidence. Among the novel findings identified by SSEA is the telomere length regulator gene TNKS. These studies are the first to use GWAS to understand the genetic diversity that accounts the phenotypic heterogeneity sickle cell anemia as estimated by an integrated model of severity. Additional validation, resequencing, and functional studies to understand the biology and reveal mechanisms by which candidate genes might have their effects are the future goals of this work.
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Registered trials
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