Beckman Research Institute, City of Hope National Medical Center, 1500 E. Duarte Road, Duarte, CA, 91010, USA.
School of Applied Science, The University of Mississippi, P.O. Box 1848, University, MS, 38677, USA.
Sci Rep. 2020 Jul 22;10(1):12223. doi: 10.1038/s41598-020-68786-6.
Whether telomere attrition reducing proliferative reserve in blood-cell progenitors is causal has important public-health implications. Mendelian randomization (MR) is an analytic technique using germline genetic variants as instrumental variables. If certain assumptions are met, estimates from MR should be free from most environmental sources of confounding and reverse causation. Here, two-sample MR is performed to test whether longer telomeres cause changes to hematological traits. Summary statistics for genetic variants strongly associated with telomere length were extracted from a genome-wide association (GWA) study for telomere length in individuals of European ancestry (n = 9190) and from GWA studies of blood-cell traits, also in those of European ancestry (n ~ 173,000 participants). A standard deviation increase in genetically influenced telomere length increased red blood cell and white blood cell counts, decreased mean corpuscular hemoglobinand mean cell volume, and had no observable impact on mean corpuscular hemoglobin concentration, red cell distribution width, hematocrit, or hemoglobin. Sensitivity tests for pleiotropic distortion were mostly inconsistent with glaring violations to the MR assumptions. Similar to germline mutations in telomere biology genes leading to bone-marrow failure, these data provide evidence that genetically influenced common variation in telomere length impacts hematologic traits in the population.
端粒磨损是否会降低血液细胞祖细胞的增殖储备，这具有重要的公共卫生意义。孟德尔随机化（MR）是一种分析技术，它使用种系遗传变异作为工具变量。如果满足某些假设，那么来自 MR 的估计值应该不受大多数环境混杂因素和反向因果关系的影响。在这里，进行了两样本 MR 分析，以测试较长的端粒是否会导致血液学特征发生变化。从欧洲血统个体的端粒长度全基因组关联（GWA）研究（n = 9190）中提取与端粒长度强烈相关的遗传变异的汇总统计数据，以及从欧洲血统个体的血液细胞特征的 GWA 研究中（n ~ 173000 名参与者）。遗传影响的端粒长度增加一个标准差会增加红细胞和白细胞计数，降低平均红细胞血红蛋白和平均细胞体积，并且对平均红细胞血红蛋白浓度、红细胞分布宽度、血细胞比容或血红蛋白没有明显影响。对多效性扭曲的敏感性测试大多与违反 MR 假设的情况不一致。与导致骨髓衰竭的端粒生物学基因突变相似，这些数据提供了证据表明，遗传影响的端粒长度常见变异会影响人群中的血液学特征。
