Yang Wei, He Xue, Yao Yuying, Lu Hongyan, Wang Yuliang, Zhang Zhanhao, Wang Yuhe, Wang Li, He Yongjun, Yuan Dongya, Jin Tianbo
Key Laboratory of Molecular Mechanism and Intervention Research for Plateau Diseases of Tibet Autonomous Region, School of Medicine, Xizang Minzu University, Xianyang, Shaanxi, 712082, People's Republic of China.
School of Basic Medical Sciences, Xizang Minzu University, Xianyang, Shaanxi, 712082, People's Republic of China.
Pharmgenomics Pers Med. 2022 Aug 3;15:743-763. doi: 10.2147/PGPM.S361809. eCollection 2022.
Hematological characteristics have positive reference value as clinical indicators in the evaluation of various diseases. The purpose of this study was to determine the gene loci associated with 20 hematological phenotypes in the Han population from northwest China.
A genome-wide association study (GWAS) was conducted on hematological indicators of 1005 Han people from northwest China. Genotyping was performed with a GeneTitan multichannel instrument and Axiom Analysis Suite 6.0. Using the 1000 Genomes Project (phase 3) as a reference, haplotype imputation was performed with IMPUTE2. SNVs (single nucleotide variants) significantly associated with hematological phenotypes were identified. The top SNV ( < 5E-7) was then selected for replication detection.
Ninety genetic variations identified in the GWAS were significantly associated with hematological indicators. Among them, only rs35289401 (CCDC157) was significantly associated (genome-wide) with red blood cell distribution width (RDW) ( = 4.21E-08). The fourteen top SNVs were selected for replication verification and were significantly associated with hematological phenotypes. However, only HBS1 L-MYB rs1331309 was significantly associated with the mean hemoglobin content ( = 6.42E-07). We also found that the mean corpuscular hemoglobin (MCH) level in the rs1331309 GG/GT genotype was significantly higher than that in the TT genotype ( = 0.023).
The GWAS identified a total of 90 genetic variants significantly associated with hematological phenotypic indicators. In particular, rs1331309 (HBS1 L-MYB) is expected to be a biomarker for monitoring the dynamics of MCH levels. This study provides a reference for related studies on the genetic structure of hematological characteristics. It provides a valuable reference for the clinical diagnosis or prediction of a variety of diseases.
血液学特征作为临床指标在各种疾病评估中具有重要参考价值。本研究旨在确定中国西北汉族人群中与20种血液学表型相关的基因位点。
对来自中国西北的1005名汉族人的血液学指标进行全基因组关联研究（GWAS）。使用GeneTitan多通道仪器和Axiom Analysis Suite 6.0进行基因分型。以千人基因组计划（第3阶段）为参考，使用IMPUTE2进行单倍型填充。识别出与血液学表型显著相关的单核苷酸变异（SNV）。然后选择顶级SNV（<5E-7）进行重复检测。
GWAS中鉴定出的90个基因变异与血液学指标显著相关。其中，只有rs35289401（CCDC157）与红细胞分布宽度（RDW）在全基因组水平上显著相关（P = 4.21E-08）。选择14个顶级SNV进行重复验证，它们与血液学表型显著相关。然而，只有HBS1L-MYB rs1331309与平均血红蛋白含量显著相关（P = 6.42E-07）。我们还发现，rs1331309的GG/GT基因型中的平均红细胞血红蛋白含量（MCH）水平显著高于TT基因型（P = 0.023）。
GWAS共鉴定出90个与血液学表型指标显著相关的基因变异。特别是，rs1331309（HBS1L-MYB）有望成为监测MCH水平动态变化的生物标志物。本研究为血液学特征的遗传结构相关研究提供了参考。为各种疾病的临床诊断或预测提供了有价值的参考。
