ArticleClinical and translational medicine2020
Genetic modifiers of long-term survival in sickle cell anemia.
Article in Clinical and translational medicine, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 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
18 citing papers in PubMed, 1 synthesis or guideline pooled it, 35 citations in OpenAlex.
- Factors associated with blood pressure variation in sickle cell disease patients: a systematic review and meta-analyses.Expert review of hematology · 2022Pooled it
- The Sickle Africa Data Coordinating Centre (SADaCC): a data science hub for interdisciplinary sickle cell disease research and training.Database : the journal of biological databases and curation · 2026Article
- The dawn of a cure for sickle cell disease through CRISPR-based treatment: A critical test of equity in public health genomics.Annals of human genetics · 2025Review
- FLT1 and other candidate fetal haemoglobin modifying loci in sickle cell disease in African ancestries.Nature communications · 2025Article
- Article
- A new era dawns on sickle cell disease in India.The Indian journal of medical research · 2023Article
- The future of sickle cell disease therapeutics rests in genomics.Disease models & mechanisms · 2023Article
- Whole genome sequencing reveals population diversity and variation in HIV-1 specific host genes.Frontiers in genetics · 2023Article
- Modulation of blood pressure regulatory genes in the Agtrap-Plod1 locus associated with a deletion in Clcn6.Physiological reports · 2022Article
- A whole genome sequencing approach to anterior cruciate ligament rupture-a twin study in two unrelated families.PloS one · 2022Article
- Distribution of HbS Allele and Haplotypes in a Multi-Ethnic Population of Guinea Bissau, West Africa: Implications for Public Health Screening.Frontiers in pediatrics · 2022Article
- Clinical characteristics and risk factors of relative systemic hypertension and hypertension among sickle cell patients in Cameroon.Frontiers in medicine · 2022Article
- Incomplete Penetrance and Variable Expressivity: From Clinical Studies to Population Cohorts.Frontiers in genetics · 2022Review
- Sickle Cell Disease in Children and Adolescents: A Review of the Historical, Clinical, and Public Health Perspective of Sub-Saharan Africa and Beyond.International journal of pediatrics · 2022Review
- Modelling the mortality of sickle cell disease in Africa.The Lancet. Haematology · 2021Article
- Evolutionary history of sickle-cell mutation: implications for global genetic medicine.Human molecular genetics · 2021Review
- Sequence three million genomes across Africa.Nature · 2021Article
- Genetic modifiers of long-term survival in sickle cell anemia.Clinical and translational medicine · 2020Article
Corrections and comments
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Authors and funding
9 authors at 2 institutions in 2 countries.
Funding
Abstract
backgroundSickle cell anemia (SCA) is a clinically heterogeneous, monogenic disorder. Medical care has less-than-optimal impact on clinical outcomes in SCA in Africa due to several factors, including patient accessibility, poor access to resources, and non-availability of specific effective interventions for SCA.
methodsAgainst this background, we investigated 192 African participants who underwent whole exome sequencing. Participants included 105 SCA patients spanning variable clinical expression: a "long survivor" group (age over 40 years), a "stroke" group (at least one episode of overt stroke), and a "random" group (patients younger than 40 years without overt cerebrovascular disease). Fifty-eight ethnically matched homozygous hemoglobin A controls were also studied. Findings were validated in an independently recruited sample of 29 SCA patients. Statistical significance of the mutational burden of deleterious and loss-of-function variants per gene against a null model was estimated for each group, and gene-set association tests were conducted to test differences between groups.
resultsIn the "long survivor" group, deleterious/loss-of-function variants were enriched in genes including CLCN6 (a voltage-dependent chloride channel for which rare deleterious variants have been associated with lower blood pressure) and OGHDL (important in arginine metabolism, which is a therapeutic target in SCA). In the "stroke" group, significant genes implicated were associated with increased activity of the blood coagulation cascade and increased complement activation, for example, SERPINC1, which encodes antithrombin. Oxidative stress and glutamate biosynthesis pathways were enriched in "long survivors" group. Published transcriptomic evidence provides functional support for the role of the identified pathways.
conclusionsThis study provides new gene sets that contribute to variability in clinical expression of SCA. Identified genes and pathways suggest new avenues for other interventions.
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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.