Trial reportPloS one2018
Analyses of genome wide association data, cytokines, and gene expression in African-Americans with benign ethnic neutropenia.
Trial report in PloS one, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers, 1 of them a synthesis that pooled it.
What it found
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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.
The trial behind it
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
24 citing papers in PubMed, 1 synthesis or guideline pooled it, 49 citations in OpenAlex.
- ACKR1/Duffy-null genotype testing for clozapine: A guideline developed by the UK Centre of Excellence in Regulatory Science and Innovation in Pharmacogenomics (CERSI-PGx).British journal of clinical pharmacology · 2026Guideline
- Trial
- Systematic Duffy phenotyping reveals high prevalence of Duffy-null genotype among neutropenic patients.Advances in laboratory medicine · 2026Article
- Characterization of the phenotypic consequences of the Duffy-null genotype.Blood advances · 2025Article
- Article
- Atypical chemokine receptors in the immune system.Nature reviews. Immunology · 2024Review
- Disparities in relapsed or refractory multiple myeloma: recommendations from an interprofessional consensus panel.Blood cancer journal · 2024Review
- Clinical and immunological features in ACKR1/DARC-associated neutropenia.Blood advances · 2024Article
- Culturally competent care for Canadian children with 'low' neutrophil counts.Paediatrics & child health · 2023Article
- Maternal pre-pregnancy BMI, offspring epigenome-wide DNA methylation, and childhood obesity: findings from the Boston Birth Cohort.BMC medicine · 2023Article
- Association between peripheral blood cytopenia and cancer mortality: A race-specific risk factor for cancer death.Cancer medicine · 2023Observational
- White blood cell ranges and frequency of neutropenia by Duffy genotype status.Blood advances · 2023Article
- Ancestry,Lupus science & medicine · 2022Article
- AI-assisted discovery of an ethnicity-influenced driver of cell transformation in esophageal and gastroesophageal junction adenocarcinomas.JCI insight · 2022Article
- Benign ethnic neutropenia: an analysis of prevalence, timing and identification accuracy in two large inner-city NHS hospitals.BMC psychiatry · 2021Observational
- Peripheral Blood Cytopenia and Risk of Cardiovascular Disease and Mortality.Journal of the American Heart Association · 2021Observational
- The Duffy-null genotype and risk of infection.Human molecular genetics · 2020Article
- Candidate SNP Markers of Atherogenesis Significantly Shifting the Affinity of TATA-Binding Protein for Human Gene Promoters show stabilizing Natural Selection as a Sum of Neutral Drift Accelerating Atherogenesis and Directional Natural Selection Slowing It.International journal of molecular sciences · 2020Article
- Prevalence of Cytopenia in the General Population-A National Health and Nutrition Examination Survey Analysis.Frontiers in oncology · 2020Article
- Benign ethnic neutropenia.Blood reviews · 2019Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
14 authors at 4 institutions in 1 country.
Funding
Abstract
backgroundBenign ethnic neutropenia (BEN) is a hematologic condition associated with people of African ancestry and specific Middle Eastern ethnic groups. Prior genetic association studies in large population showed that rs2814778 in Duffy Antigen Receptor for Chemokines (DARC) gene, specifically DARC null red cell phenotype, was associated with BEN. However, the mechanism of this red cell phenotype leading to low white cell count remained elusive.
methodsWe conducted an extreme phenotype design genome-wide association study (GWAS), analyzed ~16 million single nucleotide polymorphisms (SNP) in 1,178 African-Americans individuals from the Reasons for Geographic and Racial Differences in Stroke (REGARDS) study and replicated from 819 African-American participants in the Atherosclerosis Risk in Communities (ARIC) study. Conditional analyses on rs2814778 were performed to identify additional association signals on chromosome 1q22. In a separate cohort of healthy individuals with and without BEN, whole genome gene expression from peripheral blood neutrophils were analyzed for DARC.
resultsWe confirmed that rs2814778 in DARC was associated with BEN (p = 4.09×10-53). Conditioning on rs2814778 abolished other significant chromosome 1 associations. Inflammatory cytokines (IL-2, 6, and 10) in participants in the Howard University Family Study (HUFS) and Multi-Ethnic Study in Atherosclerosis (MESA) showed similar levels in individuals homozygous for the rs2814778 allele compared to others, indicating cytokine sink hypothesis played a minor role in leukocyte homeostasis. Gene expression in neutrophils of individuals with and without BEN was also similar except for low DARC expression in BEN, suggesting normal function. BEN neutrophils had slightly activated profiles in leukocyte migration and hematopoietic stem cell mobilization pathways (expression fold change <2).
conclusionsThese results in humans support the notion of DARC null erythroid progenitors preferentially differentiating to myeloid cells, leading to activated DARC null neutrophils egressing from circulation to the spleen, and causing relative neutropenia. Collectively, these human data sufficiently explained the mechanism DARC null red cell phenotype causing BEN and further provided a biologic basis that BEN is clinically benign.
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