Differences in Pathogenetic Mechanism Between Tibetan and Han High-Altitude Polycythemia Based on a Whole Genome-Wide Association Study.

IF 6.2 Q2 GENETICS & HEREDITY

Phenomics (Cham, Switzerland) Pub Date : 2025-02-15 eCollection Date: 2025-04-01 DOI:10.1007/s43657-024-00180-y

Zhuoma Basang, Shixuan Zhang, Xianwei Ke, Zhuoma Duoji, La Yang, Danzeng Qiangba, Yang De, Deji Gesang, Zixin Hu, Yanyun Ma, Meng Hao, Ruidong Fan, Li Han, Zeshan Lin, Yi Li, Jiucun Wang, Juan Wu

{"title":"Differences in Pathogenetic Mechanism Between Tibetan and Han High-Altitude Polycythemia Based on a Whole Genome-Wide Association Study.","authors":"Zhuoma Basang, Shixuan Zhang, Xianwei Ke, Zhuoma Duoji, La Yang, Danzeng Qiangba, Yang De, Deji Gesang, Zixin Hu, Yanyun Ma, Meng Hao, Ruidong Fan, Li Han, Zeshan Lin, Yi Li, Jiucun Wang, Juan Wu","doi":"10.1007/s43657-024-00180-y","DOIUrl":null,"url":null,"abstract":"High-altitude polycythemia (HAPC) is a prevalent chronic condition affecting individuals at high altitudes, including both highland and plains populations. This study, involving 2248 participants, explored genetic susceptibility to HAPC among ethnic groups, with 898 HAPC patients (450 Han, 448 Tibetan). The Genome-wide Association Study, encompassing 198 cases (100 Han, 98 Tibetan), identified eight Tibetan HAPC-susceptibility single-nucleotide polymorphisms and four in Han individuals. The common polymorphism locus rs7618658 (SNX4, p combine < 5 × 10-8) was validated in both populations. The investigation of Tibetan EPAS1 revealed the rs1374749 locus, along with linked loci, as a potential prevalence factor for HAPC. The GGTAC haplotype containing this locus emerged as a Protect haplotype for HAPC (p = 2.461 × 10-12, OR = 0.344). Enrichment analysis revealed that Tibetans exhibited susceptibility in oxygen-sensing pathways, such as EPAS1, associated with phenotypes like hemoglobin and platelets. In contrast, Han Chinese showed significant sensitivity in cell differentiation and angiogenesis, closely linked to hemoglobin, hematocrit, and platelets.Supplementary information: The online version contains supplementary material available at 10.1007/s43657-024-00180-y.","PeriodicalId":74435,"journal":{"name":"Phenomics (Cham, Switzerland)","volume":"5 2","pages":"169-182"},"PeriodicalIF":6.2000,"publicationDate":"2025-02-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12209065/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Phenomics (Cham, Switzerland)","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.1007/s43657-024-00180-y","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2025/4/1 0:00:00","PubModel":"eCollection","JCR":"Q2","JCRName":"GENETICS & HEREDITY","Score":null,"Total":0}

引用次数: 0

Abstract

High-altitude polycythemia (HAPC) is a prevalent chronic condition affecting individuals at high altitudes, including both highland and plains populations. This study, involving 2248 participants, explored genetic susceptibility to HAPC among ethnic groups, with 898 HAPC patients (450 Han, 448 Tibetan). The Genome-wide Association Study, encompassing 198 cases (100 Han, 98 Tibetan), identified eight Tibetan HAPC-susceptibility single-nucleotide polymorphisms and four in Han individuals. The common polymorphism locus rs7618658 (SNX4, p _combine < 5 × 10^-8) was validated in both populations. The investigation of Tibetan EPAS1 revealed the rs1374749 locus, along with linked loci, as a potential prevalence factor for HAPC. The GGTAC haplotype containing this locus emerged as a Protect haplotype for HAPC (p = 2.461 × 10^-12, OR = 0.344). Enrichment analysis revealed that Tibetans exhibited susceptibility in oxygen-sensing pathways, such as EPAS1, associated with phenotypes like hemoglobin and platelets. In contrast, Han Chinese showed significant sensitivity in cell differentiation and angiogenesis, closely linked to hemoglobin, hematocrit, and platelets.

Supplementary information: The online version contains supplementary material available at 10.1007/s43657-024-00180-y.

查看原文本刊更多论文

基于全基因组关联研究的青藏高原红细胞增多症发病机制差异

高原红细胞增多症（HAPC）是一种影响高海拔地区个体的普遍慢性疾病，包括高原和平原人群。本研究共纳入2248名受试者，共纳入898例HAPC患者（汉族450例，藏族448例），探讨不同民族间HAPC的遗传易感性。该全基因组关联研究涵盖了198例（汉族100例，藏族98例），鉴定出8个藏族hapc易感性单核苷酸多态性和4个汉族个体hapc易感性单核苷酸多态性。共同多态性位点rs7618658 （SNX4, p combine -8）在两个群体中得到验证。藏族EPAS1基因的调查显示，rs1374749位点及其连锁位点可能是HAPC的潜在流行因子。含有该位点的GGTAC单倍型成为HAPC的保护单倍型（p = 2.461 × 10-12, OR = 0.344）。富集分析显示，西藏人在与血红蛋白和血小板等表型相关的氧感应通路（如EPAS1）中表现出敏感性。相比之下，汉族在细胞分化和血管生成方面表现出显著的敏感性，与血红蛋白、红细胞压积和血小板密切相关。补充信息：在线版本包含补充资料，下载地址：10.1007/s43657-024-00180-y。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

求助全文

约1分钟内获得全文求助全文

来源期刊

Phenomics (Cham, Switzerland)

自引率

0.00%

发文量