Sex-specific genetic modifiers identified susceptibility of cold stored red blood cells to osmotic hemolysis.
Blood osmotic hemolysis
Genome-wide association study (GWAS)
NHLBI recipient epidemiology donor evaluation study (REDS)-III—red blood cell omics (RBC-Omics) study
Red blood cell susceptibility to hemolysis
Red blood cells
Sex difference
Sex-interaction
Journal
BMC genomics
ISSN: 1471-2164
Titre abrégé: BMC Genomics
Pays: England
ID NLM: 100965258
Informations de publication
Date de publication:
23 Mar 2022
23 Mar 2022
Historique:
received:
09
12
2021
accepted:
04
03
2022
entrez:
24
3
2022
pubmed:
25
3
2022
medline:
26
3
2022
Statut:
epublish
Résumé
Genetic variants have been found to influence red blood cell (RBC) susceptibility to hemolytic stress and affect transfusion outcomes and the severity of blood diseases. Males have a higher susceptibility to hemolysis than females, but little is known about the genetic mechanism contributing to the difference. To investigate the sex differences in RBC susceptibility to hemolysis, we conducted a sex-stratified genome-wide association study and a genome-wide gene-by-sex interaction scan in a multi-ethnic dataset with 12,231 blood donors who have in vitro osmotic hemolysis measurements during routine blood storage. The estimated SNP-based heritability for osmotic hemolysis was found to be significantly higher in males than in females (0.46 vs. 0.41). We identified SNPs associated with sex-specific susceptibility to osmotic hemolysis in five loci (SPTA1, KCNA6, SLC4A1, SUMO1P1, and PAX8) that impact RBC function and hemolysis. Our study established a best practice to identify sex-specific genetic modifiers for sexually dimorphic traits in datasets with mixed ancestries, providing evidence of different genetic regulations of RBC susceptibility to hemolysis between sexes. These and other variants may help explain observed sex differences in the severity of hemolytic diseases, such as sickle cell and malaria, as well as the viability of red cell storage and recovery.
Sections du résumé
BACKGROUND
BACKGROUND
Genetic variants have been found to influence red blood cell (RBC) susceptibility to hemolytic stress and affect transfusion outcomes and the severity of blood diseases. Males have a higher susceptibility to hemolysis than females, but little is known about the genetic mechanism contributing to the difference.
RESULTS
RESULTS
To investigate the sex differences in RBC susceptibility to hemolysis, we conducted a sex-stratified genome-wide association study and a genome-wide gene-by-sex interaction scan in a multi-ethnic dataset with 12,231 blood donors who have in vitro osmotic hemolysis measurements during routine blood storage. The estimated SNP-based heritability for osmotic hemolysis was found to be significantly higher in males than in females (0.46 vs. 0.41). We identified SNPs associated with sex-specific susceptibility to osmotic hemolysis in five loci (SPTA1, KCNA6, SLC4A1, SUMO1P1, and PAX8) that impact RBC function and hemolysis.
CONCLUSION
CONCLUSIONS
Our study established a best practice to identify sex-specific genetic modifiers for sexually dimorphic traits in datasets with mixed ancestries, providing evidence of different genetic regulations of RBC susceptibility to hemolysis between sexes. These and other variants may help explain observed sex differences in the severity of hemolytic diseases, such as sickle cell and malaria, as well as the viability of red cell storage and recovery.
Identifiants
pubmed: 35321643
doi: 10.1186/s12864-022-08461-4
pii: 10.1186/s12864-022-08461-4
pmc: PMC8941732
doi:
Substances chimiques
KCNA6 protein, human
0
Kv1.6 Potassium Channel
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
227Subventions
Organisme : NHLBI NIH HHS
ID : HHSN268201100001I
Pays : United States
Organisme : RTI International
ID : 0291014.202.603
Organisme : NHLBI NIH HHS
ID : R01 HL134653
Pays : United States
Organisme : NHLBI NIH HHS
ID : HHSN2682011-00001I, 00002I, 00003I, 00004I, 00005I, 00006I, 00007I, 00008I, and 00009I
Pays : United States
Organisme : WHI NIH HHS
ID : HHSN268201100001C
Pays : United States
Informations de copyright
© 2022. The Author(s).
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