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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Autor*in:	Fang Fang [verfasserIn] Kelsey Hazegh [verfasserIn] Alan E. Mast [verfasserIn] Darrell J. Triulzi [verfasserIn] Bryan R. Spencer [verfasserIn] Mark T. Gladwin [verfasserIn] Michael P. Busch [verfasserIn] Tamir Kanias [verfasserIn] Grier P. Page [verfasserIn]

Format:	E-Artikel
Sprache:	Englisch

Erschienen:	2022

Schlagwörter:	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

Übergeordnetes Werk:	In: BMC Genomics - BMC, 2003, 23(2022), 1, Seite 8
Übergeordnetes Werk:	volume:23 ; year:2022 ; number:1 ; pages:8

Links:	Link aufrufen Link aufrufen Link aufrufen Journal toc

DOI / URN:	10.1186/s12864-022-08461-4

Katalog-ID:	DOAJ048981613

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520			\|a 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.
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650		4	\|a NHLBI recipient epidemiology donor evaluation study (REDS)-III—red blood cell omics (RBC-Omics) study
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allfields	10.1186/s12864-022-08461-4 doi (DE-627)DOAJ048981613 (DE-599)DOAJfa7d522815814867aa453a23c91ff198 DE-627 ger DE-627 rakwb eng TP248.13-248.65 QH426-470 Fang Fang verfasserin aut Sex-specific genetic modifiers identified susceptibility of cold stored red blood cells to osmotic hemolysis 2022 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier 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. 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 Biotechnology Genetics Kelsey Hazegh verfasserin aut Alan E. Mast verfasserin aut Darrell J. Triulzi verfasserin aut Bryan R. Spencer verfasserin aut Mark T. Gladwin verfasserin aut Michael P. Busch verfasserin aut Tamir Kanias verfasserin aut Grier P. Page verfasserin aut In BMC Genomics BMC, 2003 23(2022), 1, Seite 8 (DE-627)326644954 (DE-600)2041499-7 14712164 nnns volume:23 year:2022 number:1 pages:8 https://doi.org/10.1186/s12864-022-08461-4 kostenfrei https://doaj.org/article/fa7d522815814867aa453a23c91ff198 kostenfrei https://doi.org/10.1186/s12864-022-08461-4 kostenfrei https://doaj.org/toc/1471-2164 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ SSG-OLC-PHA GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_702 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2031 GBV_ILN_2038 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2056 GBV_ILN_2057 GBV_ILN_2061 GBV_ILN_2111 GBV_ILN_2113 GBV_ILN_2190 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 23 2022 1 8
spelling	10.1186/s12864-022-08461-4 doi (DE-627)DOAJ048981613 (DE-599)DOAJfa7d522815814867aa453a23c91ff198 DE-627 ger DE-627 rakwb eng TP248.13-248.65 QH426-470 Fang Fang verfasserin aut Sex-specific genetic modifiers identified susceptibility of cold stored red blood cells to osmotic hemolysis 2022 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier 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. 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 Biotechnology Genetics Kelsey Hazegh verfasserin aut Alan E. Mast verfasserin aut Darrell J. Triulzi verfasserin aut Bryan R. Spencer verfasserin aut Mark T. Gladwin verfasserin aut Michael P. Busch verfasserin aut Tamir Kanias verfasserin aut Grier P. Page verfasserin aut In BMC Genomics BMC, 2003 23(2022), 1, Seite 8 (DE-627)326644954 (DE-600)2041499-7 14712164 nnns volume:23 year:2022 number:1 pages:8 https://doi.org/10.1186/s12864-022-08461-4 kostenfrei https://doaj.org/article/fa7d522815814867aa453a23c91ff198 kostenfrei https://doi.org/10.1186/s12864-022-08461-4 kostenfrei https://doaj.org/toc/1471-2164 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ SSG-OLC-PHA GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_702 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2031 GBV_ILN_2038 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2056 GBV_ILN_2057 GBV_ILN_2061 GBV_ILN_2111 GBV_ILN_2113 GBV_ILN_2190 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 23 2022 1 8
allfields_unstemmed	10.1186/s12864-022-08461-4 doi (DE-627)DOAJ048981613 (DE-599)DOAJfa7d522815814867aa453a23c91ff198 DE-627 ger DE-627 rakwb eng TP248.13-248.65 QH426-470 Fang Fang verfasserin aut Sex-specific genetic modifiers identified susceptibility of cold stored red blood cells to osmotic hemolysis 2022 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier 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. 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 Biotechnology Genetics Kelsey Hazegh verfasserin aut Alan E. Mast verfasserin aut Darrell J. Triulzi verfasserin aut Bryan R. Spencer verfasserin aut Mark T. Gladwin verfasserin aut Michael P. Busch verfasserin aut Tamir Kanias verfasserin aut Grier P. Page verfasserin aut In BMC Genomics BMC, 2003 23(2022), 1, Seite 8 (DE-627)326644954 (DE-600)2041499-7 14712164 nnns volume:23 year:2022 number:1 pages:8 https://doi.org/10.1186/s12864-022-08461-4 kostenfrei https://doaj.org/article/fa7d522815814867aa453a23c91ff198 kostenfrei https://doi.org/10.1186/s12864-022-08461-4 kostenfrei https://doaj.org/toc/1471-2164 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ SSG-OLC-PHA GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_702 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2031 GBV_ILN_2038 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2056 GBV_ILN_2057 GBV_ILN_2061 GBV_ILN_2111 GBV_ILN_2113 GBV_ILN_2190 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 23 2022 1 8
allfieldsGer	10.1186/s12864-022-08461-4 doi (DE-627)DOAJ048981613 (DE-599)DOAJfa7d522815814867aa453a23c91ff198 DE-627 ger DE-627 rakwb eng TP248.13-248.65 QH426-470 Fang Fang verfasserin aut Sex-specific genetic modifiers identified susceptibility of cold stored red blood cells to osmotic hemolysis 2022 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier 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. 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 Biotechnology Genetics Kelsey Hazegh verfasserin aut Alan E. Mast verfasserin aut Darrell J. Triulzi verfasserin aut Bryan R. Spencer verfasserin aut Mark T. Gladwin verfasserin aut Michael P. Busch verfasserin aut Tamir Kanias verfasserin aut Grier P. Page verfasserin aut In BMC Genomics BMC, 2003 23(2022), 1, Seite 8 (DE-627)326644954 (DE-600)2041499-7 14712164 nnns volume:23 year:2022 number:1 pages:8 https://doi.org/10.1186/s12864-022-08461-4 kostenfrei https://doaj.org/article/fa7d522815814867aa453a23c91ff198 kostenfrei https://doi.org/10.1186/s12864-022-08461-4 kostenfrei https://doaj.org/toc/1471-2164 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ SSG-OLC-PHA GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_702 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2031 GBV_ILN_2038 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2056 GBV_ILN_2057 GBV_ILN_2061 GBV_ILN_2111 GBV_ILN_2113 GBV_ILN_2190 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 23 2022 1 8
allfieldsSound	10.1186/s12864-022-08461-4 doi (DE-627)DOAJ048981613 (DE-599)DOAJfa7d522815814867aa453a23c91ff198 DE-627 ger DE-627 rakwb eng TP248.13-248.65 QH426-470 Fang Fang verfasserin aut Sex-specific genetic modifiers identified susceptibility of cold stored red blood cells to osmotic hemolysis 2022 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier 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. 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 Biotechnology Genetics Kelsey Hazegh verfasserin aut Alan E. Mast verfasserin aut Darrell J. Triulzi verfasserin aut Bryan R. Spencer verfasserin aut Mark T. Gladwin verfasserin aut Michael P. Busch verfasserin aut Tamir Kanias verfasserin aut Grier P. Page verfasserin aut In BMC Genomics BMC, 2003 23(2022), 1, Seite 8 (DE-627)326644954 (DE-600)2041499-7 14712164 nnns volume:23 year:2022 number:1 pages:8 https://doi.org/10.1186/s12864-022-08461-4 kostenfrei https://doaj.org/article/fa7d522815814867aa453a23c91ff198 kostenfrei https://doi.org/10.1186/s12864-022-08461-4 kostenfrei https://doaj.org/toc/1471-2164 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ SSG-OLC-PHA GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_702 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2031 GBV_ILN_2038 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2056 GBV_ILN_2057 GBV_ILN_2061 GBV_ILN_2111 GBV_ILN_2113 GBV_ILN_2190 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 23 2022 1 8
language	English
source	In BMC Genomics 23(2022), 1, Seite 8 volume:23 year:2022 number:1 pages:8
sourceStr	In BMC Genomics 23(2022), 1, Seite 8 volume:23 year:2022 number:1 pages:8
format_phy_str_mv	Article
institution	findex.gbv.de
topic_facet	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 Biotechnology Genetics
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container_title	BMC Genomics
authorswithroles_txt_mv	Fang Fang @@aut@@ Kelsey Hazegh @@aut@@ Alan E. Mast @@aut@@ Darrell J. Triulzi @@aut@@ Bryan R. Spencer @@aut@@ Mark T. Gladwin @@aut@@ Michael P. Busch @@aut@@ Tamir Kanias @@aut@@ Grier P. Page @@aut@@
publishDateDaySort_date	2022-01-01T00:00:00Z
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language_de	englisch
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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. 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callnumber-first	T - Technology
author	Fang Fang
spellingShingle	Fang Fang misc TP248.13-248.65 misc QH426-470 misc Red blood cell susceptibility to hemolysis misc Genome-wide association study (GWAS) misc Sex difference misc NHLBI recipient epidemiology donor evaluation study (REDS)-III—red blood cell omics (RBC-Omics) study misc Sex-interaction misc Red blood cells misc Biotechnology misc Genetics Sex-specific genetic modifiers identified susceptibility of cold stored red blood cells to osmotic hemolysis
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topic_title	TP248.13-248.65 QH426-470 Sex-specific genetic modifiers identified susceptibility of cold stored red blood cells to osmotic hemolysis 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
topic	misc TP248.13-248.65 misc QH426-470 misc Red blood cell susceptibility to hemolysis misc Genome-wide association study (GWAS) misc Sex difference misc NHLBI recipient epidemiology donor evaluation study (REDS)-III—red blood cell omics (RBC-Omics) study misc Sex-interaction misc Red blood cells misc Biotechnology misc Genetics
topic_unstemmed	misc TP248.13-248.65 misc QH426-470 misc Red blood cell susceptibility to hemolysis misc Genome-wide association study (GWAS) misc Sex difference misc NHLBI recipient epidemiology donor evaluation study (REDS)-III—red blood cell omics (RBC-Omics) study misc Sex-interaction misc Red blood cells misc Biotechnology misc Genetics
topic_browse	misc TP248.13-248.65 misc QH426-470 misc Red blood cell susceptibility to hemolysis misc Genome-wide association study (GWAS) misc Sex difference misc NHLBI recipient epidemiology donor evaluation study (REDS)-III—red blood cell omics (RBC-Omics) study misc Sex-interaction misc Red blood cells misc Biotechnology misc Genetics
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title	Sex-specific genetic modifiers identified susceptibility of cold stored red blood cells to osmotic hemolysis
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title_full	Sex-specific genetic modifiers identified susceptibility of cold stored red blood cells to osmotic hemolysis
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author_browse	Fang Fang Kelsey Hazegh Alan E. Mast Darrell J. Triulzi Bryan R. Spencer Mark T. Gladwin Michael P. Busch Tamir Kanias Grier P. Page
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title_sort	sex-specific genetic modifiers identified susceptibility of cold stored red blood cells to osmotic hemolysis
callnumber	TP248.13-248.65
title_auth	Sex-specific genetic modifiers identified susceptibility of cold stored red blood cells to osmotic hemolysis
abstract	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.
abstractGer	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.
abstract_unstemmed	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.
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title_short	Sex-specific genetic modifiers identified susceptibility of cold stored red blood cells to osmotic hemolysis
url	https://doi.org/10.1186/s12864-022-08461-4 https://doaj.org/article/fa7d522815814867aa453a23c91ff198 https://doaj.org/toc/1471-2164
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Sex-specific genetic modifiers identified susceptibility of cold stored red blood cells to osmotic hemolysis

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