Sex-specific genetic modifiers identified susceptibility of cold stored red blood cells to osmotic hemolysis.
Sex-specific genetic modifiers identified susceptibility of cold stored red blood cells to osmotic hemolysis.
复制标题
DOI：
10.1186/s12864-022-08461-4
复制
发表时间：
2022-03-23
期刊：
影响因子：
4.4
通讯作者：
Page GP
中科院分区：
文献类型：
--
作者：
Fang F;Hazegh K;Mast AE;Triulzi DJ;Spencer BR;Gladwin MT;Busch MP;Kanias T;Page GP
已发现遗传变异影响红细胞（RBC）对溶血应激的敏感性，并影响输血结果和血液疾病的严重程度。男性比女性对溶血的易感性更高，但对导致这种差异的遗传机制知之甚少。为了研究红细胞对溶血敏感性的性别差异，我们在一个多种族数据集中进行了一项性别分层的全基因组关联研究和全基因组基因与性别的相互作用扫描，该数据集中有12，231名献血者，他们在常规血液储存期间进行了体外渗透性溶血测量。据估计，基于SNP的渗透性溶血的遗传力被认为是显着高于男性比女性（0.46与0.41）。我们在影响RBC功能和溶血的5个位点（SPTA 1、KCNA 6、SLC 4A 1、SUMO 1 P1和PAX 8）中鉴定了与性别特异性渗透性溶血易感性相关的SNP。我们的研究建立了一个最佳实践，以确定性别特异性遗传修饰剂的混合祖先的数据集中的性二态性状，提供了不同的遗传调控的证据，性别之间的红细胞溶血的易感性。这些和其他变异可能有助于解释观察到的溶血性疾病（如镰状细胞和疟疾）严重程度的性别差异，以及红细胞储存和恢复的活力。在线版本包含补充材料，可通过10.1186/s12864-022-08461-4获得。
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. The online version contains supplementary material available at 10.1186/s12864-022-08461-4.
登录
查看更多内容
影响因子：
30.8
作者：
Bulik-Sullivan, Brendan K.;Loh, Po-Ru;Finucane, Hilary K.;Ripke, Stephan;Yang, Jian;Patterson, Nick;Daly, Mark J.;Price, Alkes L.;Neale, Benjamin M.
通讯作者：
Neale, Benjamin M.
影响因子：
37.8
作者：
Gladwin, MT;Schechter, AN;Cannon, RO
通讯作者：
Cannon, RO
影响因子：
14.9
作者：
Buniello, Annalisa;MacArthur, Jacqueline A. L.;Parkinson, Helen
通讯作者：
Parkinson, Helen
影响因子：
2.9
作者：
Kanias, Tamir;Sinchar, Derek;Gladwin, Mark T.
通讯作者：
Gladwin, Mark T.
影响因子：
2.7
作者：
Jordan, A.;Chen, D.;Acker, J. P.
通讯作者：
Acker, J. P.