为中国人群量身定制单基因疾病携带者筛查面板：考虑区域差异的重要性。

IF 1.6 4区医学 Q3 GENETICS & HEREDITY

European journal of medical genetics Pub Date : 2025-02-18 DOI:10.1016/j.ejmg.2025.105002

Wei Hou , Xiaolin Fu , Xiaoxiao Xie , Chunyan Zhang , Manli Zhang , Rui Xiao , Yanping Lu

{"title":"为中国人群量身定制单基因疾病携带者筛查面板：考虑区域差异的重要性。","authors":"Wei Hou , Xiaolin Fu , Xiaoxiao Xie , Chunyan Zhang , Manli Zhang , Rui Xiao , Yanping Lu","doi":"10.1016/j.ejmg.2025.105002","DOIUrl":null,"url":null,"abstract":"<div><div>Carrier screening for monogenic diseases is becoming increasingly important in preventive medicine, yet selecting appropriate target genes remains a complex task, especially in countries with significant ethnic and geographic diversity such as China. This study aimed to develop a strategy to screen for carrier screening target genes suitable for the Chinese population, considering regional variations in carrier frequencies (CFs).</div><div>We analyzed a dataset from a large-scale, multicenter carrier screening study, encompassing 33,104 individuals from different regions of China and carrier status for 223 genes. We focused on the CFs of these genes across regions. The study first stratified the population based on participants' self-reported ancestral places and then applied consensus k-means clustering analysis to the CF characteristics of these regions. This approach enabled us to identify distinct regional subpopulations with shared genetic backgrounds.</div><div>The results showed that the regions clustered into three subpopulations (North, South, and Far South) based on CF characteristics, and 44 genes exhibited significant CF differences across these subpopulations (α = 0.05). Applying an overall CF threshold without considering regional diversity would have excluded 11 regionally prevalent genes from the screening panel. By incorporating regional variations, we accurately identified 58 genes that met the recommended CF criteria (autosomal gene CF > 1/200, X-linked gene CF > 1/40,000) in at least one subpopulation.</div><div>This study emphasizes the importance of considering regional diversity when designing carrier screening panels for monogenic diseases in China. Our proposed strategy, combining regional stratification and clustering analysis, provides a more precise method for selecting target genes, thereby enhancing the effectiveness and relevance of screening programs across different Chinese populations.</div></div>","PeriodicalId":11916,"journal":{"name":"European journal of medical genetics","volume":"74 ","pages":"Article 105002"},"PeriodicalIF":1.6000,"publicationDate":"2025-02-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Tailoring monogenic disease carrier screening panels for Chinese populations: The importance of considering regional differences\",\"authors\":\"Wei Hou , Xiaolin Fu , Xiaoxiao Xie , Chunyan Zhang , Manli Zhang , Rui Xiao , Yanping Lu\",\"doi\":\"10.1016/j.ejmg.2025.105002\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><div>Carrier screening for monogenic diseases is becoming increasingly important in preventive medicine, yet selecting appropriate target genes remains a complex task, especially in countries with significant ethnic and geographic diversity such as China. This study aimed to develop a strategy to screen for carrier screening target genes suitable for the Chinese population, considering regional variations in carrier frequencies (CFs).</div><div>We analyzed a dataset from a large-scale, multicenter carrier screening study, encompassing 33,104 individuals from different regions of China and carrier status for 223 genes. We focused on the CFs of these genes across regions. The study first stratified the population based on participants' self-reported ancestral places and then applied consensus k-means clustering analysis to the CF characteristics of these regions. This approach enabled us to identify distinct regional subpopulations with shared genetic backgrounds.</div><div>The results showed that the regions clustered into three subpopulations (North, South, and Far South) based on CF characteristics, and 44 genes exhibited significant CF differences across these subpopulations (α = 0.05). Applying an overall CF threshold without considering regional diversity would have excluded 11 regionally prevalent genes from the screening panel. By incorporating regional variations, we accurately identified 58 genes that met the recommended CF criteria (autosomal gene CF > 1/200, X-linked gene CF > 1/40,000) in at least one subpopulation.</div><div>This study emphasizes the importance of considering regional diversity when designing carrier screening panels for monogenic diseases in China. Our proposed strategy, combining regional stratification and clustering analysis, provides a more precise method for selecting target genes, thereby enhancing the effectiveness and relevance of screening programs across different Chinese populations.</div></div>\",\"PeriodicalId\":11916,\"journal\":{\"name\":\"European journal of medical genetics\",\"volume\":\"74 \",\"pages\":\"Article 105002\"},\"PeriodicalIF\":1.6000,\"publicationDate\":\"2025-02-18\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"European journal of medical genetics\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://www.sciencedirect.com/science/article/pii/S1769721225000096\",\"RegionNum\":4,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q3\",\"JCRName\":\"GENETICS & HEREDITY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"European journal of medical genetics","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S1769721225000096","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q3","JCRName":"GENETICS & HEREDITY","Score":null,"Total":0}

引用次数: 0

摘要

单基因疾病的携带者筛查在预防医学中变得越来越重要，但选择合适的靶基因仍然是一项复杂的任务，特别是在像中国这样具有显著种族和地理多样性的国家。本研究旨在考虑携带者频率（CFs）的区域差异，制定适合中国人群的携带者筛选靶基因筛选策略。我们分析了来自一项大规模、多中心的携带者筛选研究的数据集，其中包括来自中国不同地区的33104名个体和223个基因的携带者状态。我们关注的是这些基因在不同地区的CFs。该研究首先根据参与者自述的祖籍地对人群进行分层，然后对这些地区的CF特征应用共识k-均值聚类分析。这种方法使我们能够识别具有共同遗传背景的不同区域亚群。结果表明，根据CF特征，该区域可分为北、南、远南3个亚群，其中44个基因在这些亚群中表现出显著的CF差异（α=0.05）。在不考虑区域多样性的情况下应用总体CF阈值将会从筛选小组中排除11个区域流行基因。通过结合区域差异，我们在至少一个亚群中准确地鉴定出58个基因符合推荐的CF标准（常染色体基因CF > 1/200， x连锁基因CF > 1/40,000）。本研究强调了在设计中国单基因疾病携带者筛选面板时考虑区域多样性的重要性。我们提出的策略，结合区域分层和聚类分析，为选择靶基因提供了更精确的方法，从而提高了筛查方案在不同中国人群中的有效性和相关性。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

查看原文本刊更多论文

Tailoring monogenic disease carrier screening panels for Chinese populations: The importance of considering regional differences

Carrier screening for monogenic diseases is becoming increasingly important in preventive medicine, yet selecting appropriate target genes remains a complex task, especially in countries with significant ethnic and geographic diversity such as China. This study aimed to develop a strategy to screen for carrier screening target genes suitable for the Chinese population, considering regional variations in carrier frequencies (CFs).

We analyzed a dataset from a large-scale, multicenter carrier screening study, encompassing 33,104 individuals from different regions of China and carrier status for 223 genes. We focused on the CFs of these genes across regions. The study first stratified the population based on participants' self-reported ancestral places and then applied consensus k-means clustering analysis to the CF characteristics of these regions. This approach enabled us to identify distinct regional subpopulations with shared genetic backgrounds.

The results showed that the regions clustered into three subpopulations (North, South, and Far South) based on CF characteristics, and 44 genes exhibited significant CF differences across these subpopulations (α = 0.05). Applying an overall CF threshold without considering regional diversity would have excluded 11 regionally prevalent genes from the screening panel. By incorporating regional variations, we accurately identified 58 genes that met the recommended CF criteria (autosomal gene CF > 1/200, X-linked gene CF > 1/40,000) in at least one subpopulation.

This study emphasizes the importance of considering regional diversity when designing carrier screening panels for monogenic diseases in China. Our proposed strategy, combining regional stratification and clustering analysis, provides a more precise method for selecting target genes, thereby enhancing the effectiveness and relevance of screening programs across different Chinese populations.

求助全文

通过发布文献求助，成功后即可免费获取论文全文。去求助

来源期刊

European journal of medical genetics 医学-遗传学

CiteScore

4.10

自引率

0.00%

发文量

193

审稿时长

66 days

期刊介绍： The European Journal of Medical Genetics (EJMG) is a peer-reviewed journal that publishes articles in English on various aspects of human and medical genetics and of the genetics of experimental models. Original clinical and experimental research articles, short clinical reports, review articles and letters to the editor are welcome on topics such as : • Dysmorphology and syndrome delineation • Molecular genetics and molecular cytogenetics of inherited disorders • Clinical applications of genomics and nextgen sequencing technologies • Syndromal cancer genetics • Behavioral genetics • Community genetics • Fetal pathology and prenatal diagnosis • Genetic counseling.