Whole-genome Sequencing Association Analysis of Quantitative Platelet Traits in A Large Cohort of β-thalassemia
Platelets act as a crucial indicator for monitoring hypercoagulability and thrombosis and a key target for pharmacological intervention. Genotype-phenotype association studies have confirmed that platelet traits are quantitatively regulated by multiple genes. However, there is currently a lack of genetic studies on the heterogeneity of platelet traits in β-thalassemia under a hypercoagulable state. Here, we studied the phenotypic heterogeneity of platelet count (PLT) and mean platelet volume (MPV) in a cohort of 1020 β-thalassemia patients. We further performed a functionally informed whole-genome sequencing (WGS) association analysis of common variants and rare variants for PLT and MPV in 916 patients through integrative analysis of WGS data and functional annotation data. Extreme phenotypic heterogeneity of platelet traits was observed in β-thalassemia patients. Additionally, the common variant-based gene-level analysis identified RNF144B as a novel gene associated with MPV. The rare variant analysis identified several novel associations in both coding and noncoding regions, including missense rare variants of PPP2R5C associated with PLT and missense rare variants of TSSK1B associated with MPV. In conclusion, this comprehensive and systematic whole-genome scan of platelet traits in the β-thalassemia cohort reveals the specific genetic regulation of platelet traits in the context of β-thalassemia, providing potential targets for intervention.
Authors
- Mingyan Fang (ORCID: https://orcid.org/0000-0001-7185-6445)
- Qianqian Zhang (ORCID: https://orcid.org/0000-0003-1294-7325)
- Tianyu Zhong (ORCID: https://orcid.org/0000-0003-1934-0032)
- Bin Lin (ORCID: https://orcid.org/0000-0002-8032-937X)
- Liuhua Liao
- Xiangmin Xu (ORCID: https://orcid.org/0000-0003-2775-8228)
- Mengyang Song
- Xin Jin (ORCID: https://orcid.org/0000-0001-7554-4975)
- Deguo Tang
- Jinquan Lao
- Chao Shi Niu (ORCID: https://orcid.org/0009-0005-6131-8113)
- Zhixiang Liu (ORCID: https://orcid.org/0000-0003-4121-6134)
- Li Huang (ORCID: https://orcid.org/0000-0002-5964-7090)
- Juanjuan Chen (ORCID: https://orcid.org/0000-0002-5042-996X)
- Chengwu Fan
- Xiaoqin Feng (ORCID: https://orcid.org/0000-0003-1166-0138)
- Binbin Huang (ORCID: https://orcid.org/0000-0002-8524-2425)
- Weijian Zhu (ORCID: https://orcid.org/0000-0002-2120-5860)
- Xingmin Wang (ORCID: https://orcid.org/0000-0001-9327-9159)
- Yushan Huang (ORCID: https://orcid.org/0000-0002-2876-9079)
- Caiyun Li (ORCID: https://orcid.org/0000-0002-6863-2173)
- Xian‐Ming Chen (ORCID: https://orcid.org/0000-0001-9848-2244)
- Xing‐Jiang Long
- Yuhua Ye (ORCID: https://orcid.org/0000-0002-8037-2175)
- Lian Yu (ORCID: https://orcid.org/0000-0002-8808-8048)
- Xiaoyun Hua
- Yueyan Huang (ORCID: https://orcid.org/0000-0003-4489-4942)
- Xinhua Zhang
- Zilin Li
- Wei Zhang (ORCID: https://orcid.org/0000-0002-4280-1442)
Institutions
- Fujian Medical University (CN)
- Guilin Medical University (CN)
- Longyan University (CN)
- Northeast Normal University (CN)
- Liuzhou Maternal and Child Health Hospital (CN)
- Liuzhou General Hospital (CN)
- Nanfang Hospital (CN)
- Zhuhai People's Hospital (CN)
- Taiyuan Maternity and Child Care Hospital (CN)
- Jingzhou Maternal and Child Health Hospital (CN)
- Guangzhou Automobile Group (China) (CN)
- First Affiliated Hospital of Fujian Medical University (CN)
- Dongguan People’s Hospital (CN)
- Botswana Geoscience Institute (BW)
- Affiliated Hospital of Youjiang Medical University for Nationalities (CN)
- First Affiliated Hospital of Gannan Medical University (CN)
- The Second Nanning People's Hospital (CN)
- Fourth Affiliated Hospital of Guangxi Medical University (CN)
- Huizhou Central People's Hospital (CN)
- Affiliated Hospital of Guilin Medical College (CN)
- First People's Hospital of Nanning (CN)
- Chenzhou First People's Hospital (CN)
- 303 Hospital of People's Liberation Army (CN)
- Shenzhen Second People's Hospital (CN)
- University of Chinese Academy of Sciences (CN)
- BGI Research (CN)
- Southern Medical University (CN)
Publication Details
- Journal
- Genomics Proteomics & Bioinformatics
- Published
- 2024-09-27
- DOI
- https://doi.org/10.1093/gpbjnl/qzae065
- Citations
- 3
- Primary Topic
- Myeloproliferative Neoplasms: Diagnosis and Treatment
- Type
- article
- Field-Weighted Citation Impact
- 1.31
Funders
- National Natural Science Foundation of China
- China Postdoctoral Science Foundation
- Basic and Applied Basic Research Foundation of Guangdong Province