ArticleBlood advances2021
A polygenic score for acute vaso-occlusive pain in pediatric sickle cell disease.
Article in Blood advances, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers, 2 of them syntheses that pooled it.
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Who cites it
21 citing papers in PubMed, 2 syntheses or guidelines pooled it, 25 citations in OpenAlex.
- Genetic Polymorphisms Associated with Fetal Hemoglobin (HbF) Levels and F-Cell Numbers: A Systematic Review of Genome-Wide Association Studies.International journal of molecular sciences · 2024Pooled it
- Genetic Variation and Sickle Cell Disease Severity: A Systematic Review and Meta-Analysis.JAMA network open · 2023Pooled it
- Article
- Clinical determinants of severe vaso-occlusive crisis in pediatric sickle cell anemia: a retrospective cohort study.Translational pediatrics · 2026Article
- A genetic risk score based on BCL11A and HBS1L-MYB variants predicts clinical severity in Brazilian sickle cell anaemia patients.British journal of haematology · 2026Article
- Increased Endothelin-1 and High-Risk APOL1 Variants Contribute to Albuminuria in Pediatric and Young Adults with Sickle Cell Anemia.Clinical journal of the American Society of Nephrology : CJASN · 2026Article
- Review
- Accelerating novel therapies for sickle cell disease with RWE: ASH RC Data Hub as a strategically coordinated registry network.Blood advances · 2026Article
- Development of Polygenic Risk Score for Persistent Albuminuria in Children and Adults With Sickle Cell Anemia.American journal of hematology · 2025Observational
- Genetic Modifiers Associated with Vaso-Occlusive Crises and Acute Pain Phenomena in Sickle Cell Disease: A Scoping Review.International journal of molecular sciences · 2025Article
- A Novel One-Sample Mendelian Randomization Approach for Count-Type Outcomes That Is Robust to Correlated and Uncorrelated Pleiotropic Effects.Genetic epidemiology · 2025Article
- Burden of vaso-occlusive crisis, its management and impact on quality of life of Indian sickle cell disease patients.British journal of haematology · 2025Observational
- Article
- Transcriptional regulators of fetal hemoglobin.Hematology, transfusion and cell therapy · 2024Review
- Can we use biomarkers to identify those at risk of acute pain from sickle cell disease?Expert review of hematology · 2024Review
- Catechol-O-methyltransferase gene (COMT) is associated with neurocognitive functioning in patients with sickle cell disease.Current research in translational medicine · 2024Article
- The genetic dissection of fetal haemoglobin persistence in sickle cell disease in Nigeria.Human molecular genetics · 2024Article
- Variation and impact of polygenic hematologic traits in monogenic sickle cell disease.Haematologica · 2023Article
- Single nucleotide polymorphisms and sickle cell disease-related pain: a systematic review.Frontiers in pain research (Lausanne, Switzerland) · 2023Review
- Fetal hemoglobin modulates neurocognitive performance in sickle cell anemiaCurrent research in translational medicine · 2022Article
Corrections and comments
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Authors and funding
43 authors at 9 institutions in 3 countries.
Funding
Abstract
Individuals with monogenic disorders can experience variable phenotypes that are influenced by genetic variation. To investigate this in sickle cell disease (SCD), we performed whole-genome sequencing (WGS) of 722 individuals with hemoglobin HbSS or HbSβ0-thalassemia from Baylor College of Medicine and from the St. Jude Children's Research Hospital Sickle Cell Clinical Research and Intervention Program (SCCRIP) longitudinal cohort study. We developed pipelines to identify genetic variants that modulate sickle hemoglobin polymerization in red blood cells and combined these with pain-associated variants to build a polygenic score (PGS) for acute vaso-occlusive pain (VOP). Overall, we interrogated the α-thalassemia deletion -α3.7 and 133 candidate single-nucleotide polymorphisms (SNPs) across 66 genes for associations with VOP in 327 SCCRIP participants followed longitudinally over 6 years. Twenty-one SNPs in 9 loci were associated with VOP, including 3 (BCL11A, MYB, and the β-like globin gene cluster) that regulate erythrocyte fetal hemoglobin (HbF) levels and 6 (COMT, TBC1D1, KCNJ6, FAAH, NR3C1, and IL1A) that were associated previously with various pain syndromes. An unweighted PGS integrating all 21 SNPs was associated with the VOP event rate (estimate, 0.35; standard error, 0.04; P = 5.9 × 10-14) and VOP event occurrence (estimate, 0.42; standard error, 0.06; P = 4.1 × 10-13). These associations were stronger than those of any single locus. Our findings provide insights into the genetic modulation of VOP in children with SCD. More generally, we demonstrate the utility of WGS for investigating genetic contributions to the variable expression of SCD-associated morbidities.
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