Sex-specific genetic modifiers identified susceptibility of cold stored red blood cells to osmotic hemolysis
Abstract 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...
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| Format: | Article |
| Language: | English |
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BMC
2022-03-01
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| Series: | BMC Genomics |
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| Online Access: | https://doi.org/10.1186/s12864-022-08461-4 |
| _version_ | 1818356682961453056 |
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| author | Fang Fang Kelsey Hazegh Alan E. Mast Darrell J. Triulzi Bryan R. Spencer Mark T. Gladwin Michael P. Busch Tamir Kanias Grier P. Page |
| author_facet | Fang Fang Kelsey Hazegh Alan E. Mast Darrell J. Triulzi Bryan R. Spencer Mark T. Gladwin Michael P. Busch Tamir Kanias Grier P. Page |
| author_sort | Fang Fang |
| collection | DOAJ |
| description | Abstract 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 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 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. |
| first_indexed | 2024-12-13T20:01:06Z |
| format | Article |
| id | doaj.art-fa7d522815814867aa453a23c91ff198 |
| institution | Directory Open Access Journal |
| issn | 1471-2164 |
| language | English |
| last_indexed | 2024-12-13T20:01:06Z |
| publishDate | 2022-03-01 |
| publisher | BMC |
| record_format | Article |
| series | BMC Genomics |
| spelling | doaj.art-fa7d522815814867aa453a23c91ff1982022-12-21T23:33:11ZengBMCBMC Genomics1471-21642022-03-012311810.1186/s12864-022-08461-4Sex-specific genetic modifiers identified susceptibility of cold stored red blood cells to osmotic hemolysisFang Fang0Kelsey Hazegh1Alan E. Mast2Darrell J. Triulzi3Bryan R. Spencer4Mark T. Gladwin5Michael P. Busch6Tamir Kanias7Grier P. Page8GenOmics, Bioinformatics, and Translational Research Center, RTI InternationalVitalant Research InstituteVersiti Blood Research Institute, Blood Center of WisconsinDepartment of Pathology, University of PittsburghAmerican Red CrossPittsburgh Heart, Lung, and Blood Vascular Medicine Institute, University of PittsburghVitalant Research InstituteVitalant Research InstituteGenOmics, Bioinformatics, and Translational Research Center, RTI InternationalAbstract 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 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 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.https://doi.org/10.1186/s12864-022-08461-4Red blood cell susceptibility to hemolysisGenome-wide association study (GWAS)Sex differenceNHLBI recipient epidemiology donor evaluation study (REDS)-III—red blood cell omics (RBC-Omics) studySex-interactionRed blood cells |
| spellingShingle | Fang Fang Kelsey Hazegh Alan E. Mast Darrell J. Triulzi Bryan R. Spencer Mark T. Gladwin Michael P. Busch Tamir Kanias Grier P. Page Sex-specific genetic modifiers identified susceptibility of cold stored red blood cells to osmotic hemolysis BMC Genomics Red blood cell susceptibility to hemolysis Genome-wide association study (GWAS) Sex difference NHLBI recipient epidemiology donor evaluation study (REDS)-III—red blood cell omics (RBC-Omics) study Sex-interaction Red blood cells |
| title | Sex-specific genetic modifiers identified susceptibility of cold stored red blood cells to osmotic hemolysis |
| title_full | Sex-specific genetic modifiers identified susceptibility of cold stored red blood cells to osmotic hemolysis |
| title_fullStr | Sex-specific genetic modifiers identified susceptibility of cold stored red blood cells to osmotic hemolysis |
| title_full_unstemmed | Sex-specific genetic modifiers identified susceptibility of cold stored red blood cells to osmotic hemolysis |
| title_short | Sex-specific genetic modifiers identified susceptibility of cold stored red blood cells to osmotic hemolysis |
| title_sort | sex specific genetic modifiers identified susceptibility of cold stored red blood cells to osmotic hemolysis |
| topic | Red blood cell susceptibility to hemolysis Genome-wide association study (GWAS) Sex difference NHLBI recipient epidemiology donor evaluation study (REDS)-III—red blood cell omics (RBC-Omics) study Sex-interaction Red blood cells |
| url | https://doi.org/10.1186/s12864-022-08461-4 |
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