Evidence map›Paper›PMID 39279196›Full record

ArticleBritish journal of haematology2024

Genetic variants associated with white blood cell count amongst individuals with sickle cell disease.

Mina Cintho Ozahata, Yuelong Guo, Isabel Gomes, Barbara Malta, André Belisário, Luiz Amorim, Dahra Teles, Miriam Park, Shannon Kelly, Ester C Sabino and 4 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in British journal of haematology, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

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.

2 · The registry

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.

3 · Its place in the literature

Who cites it

0 citing papers in PubMed.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

14 authors.

Mina Cintho OzahataUniversity of São Paulo, São Paulo, Brazil.ORCID https://orcid.org/0000-0002-1272-2380
Yuelong GuoRTI International, Atlanta, Georgia, USA.
Isabel GomesFederal University of Minas Gerais, Minas Gerais, Brazil.
Barbara MaltaFundação Hemominas, Belo Horizonte, Minas Gerais, Brazil.
André BelisárioFundação Hemominas, Belo Horizonte, Minas Gerais, Brazil.ORCID https://orcid.org/0000-0003-0166-4258
Luiz AmorimHEMORIO, Rio de Janeiro, Brazil.
Dahra TelesFundação HEMOPE, Recife, Pernambuco, Brazil.
Miriam ParkChildren Institute-University of São Paulo, São Paulo, Brazil.
Shannon KellyBCHO - UCSF Benioff Children's Hospital Oakland, Oakland, California, USA.
Ester C SabinoUniversity of São Paulo, São Paulo, Brazil.
Grier P PageRTI International, Atlanta, Georgia, USA.
Brian CusterVitalant Research Institute, San Francisco, California, USA.
Carla L DinardoFundação Pró-Sangue, São Paulo, Brazil.ORCID https://orcid.org/0000-0002-0453-7863
International Component of the NHLBI Recipient Epidemiology and Donor Evaluation Study (REDS‐III) and for the TOPMed (NHLBI TransOmics for Precision Medicine) SCD working

Funding

Studies of Rare Genetic Variation in the Isolated Population of SardiniaR01HL117626 · NHLBI · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI ABECASIS, GONCALO · 2013 to 2016
$10.5M
Rare variants and NHLBI traits in deeply phenotyped cohortsR01HL120393 · NHLBI · UNIVERSITY OF WASHINGTON · PI PSATY, BRUCE M, RICE, KENNETH M. · 2014 to 2016
$8.9M
Rare variants and NHLBI traits in deeply phenotyped cohortsU01HL120393 · NHLBI · UNIVERSITY OF WASHINGTON · PI PSATY, BRUCE M, RICE, KENNETH M. · 2017 to 2018
$5.6M
NHLBI NIH HHS HHSN268201100001INHLBI NIH HHS HHSN268201100002INHLBI NIH HHS HHSN268201100005INHLBI NIH HHS HHSN268201100007INHLBI NIH HHS HHSN268201100008INHLBI NIH HHS HHSN268201100009INHLBI NIH HHS HHSN2682011#x2010;00001INHLBI NIH HHS HHSN2682011#x2010;00002INHLBI NIH HHS HHSN2682011#x2010;00003INHLBI NIH HHS HHSN2682011#x2010;00004INHLBI NIH HHS HHSN2682011#x2010;00005INHLBI NIH HHS HHSN2682011#x2010;00006INHLBI NIH HHS HHSN2682011#x2010;00007INHLBI NIH HHS HHSN2682011#x2010;00008INHLBI NIH HHS HHSN2682011#x2010;00009INHLBI NIH HHS HHSN268201500015CNHLBI NIH HHS HHSN268201800001CNHLBI NIH HHS R01 HL117626NHLBI NIH HHS R01 HL120393NHLBI NIH HHS U01 HL120393WHI NIH HHS HHSN268201100001C
6 · The paper itself

Abstract

backgroundSickle cell disease (SCD) is a Mendelian disorder characterized by a point mutation in the β-globin gene that leads to sickling of erythrocytes. Several studies have shown that absolute neutrophil count is strongly associated with clinical severity of SCD, suggesting an apparent role of white blood cells (WBC) in SCD pathology. However, the mechanism by which genetic variants lead to WBC count differences in SCD patients remains unclear.

methodsGenome-wide association (GWA) analyses were carried out amongst a cohort of 2409 Brazil SCD participants. Association of WBC count and genetic markers were investigated in homozygous sickle cell anaemia participants and compound heterozygous sickle cell haemoglobin C participants.

resultsGWA analysis showed that variants in genes TERT, ACKR1, and FAM3C are associated with WBC count variation. The well-studied association between WBC count and Duffy null phenotype (variant in ACKR1) in healthy populations was replicated, reinforcing the influence of the SNP rs2814778 (T>C) in WBC count.

conclusionGenetics plays an important role in regulating WBC count in patients with SCD. Our results point to possible mechanisms involved in WBC count variation and as increased WBC count is associated with more severe SCD, these results could suggest potential therapeutic targets for individuals with SCD.

Indexed as

Anemia, Sickle CellGenome-Wide Association StudyPolymorphism, Single NucleotideAdolescentAdultBrazilChildDuffy Blood-Group SystemFemaleHumansLeukocyte CountMaleReceptors, Cell SurfaceTelomeraseYoung AdultACKR1 protein, humanDuffy Blood-Group SystemReceptors, Cell SurfaceTelomeraseTERT protein, humanGWASsickle cell diseaseWBC

Identifiers

PMID39279196
PMCPMC11568933

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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.