基于DNA变异在亚欧混合人群中预测男性型脱发
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1.1)中国科学院北京基因组研究所国家生物信息中心,中国科学院精准基因组医学重点实验室,中国科学院大学生命科学学院,北京 100101;2.2)公安部物证鉴定中心,现场物证溯源技术国家工程实验室,法医遗传学公安部重点实验室,北京 100038;3.3)湖南省公安厅刑侦总队,长沙 410001

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国家重点研发项目,现场物证溯源技术国家工程实验室开放课题,国家自然科学基金,中央级公益性科研院所基本科研业务费项目,中国科学院基因组与精准医学重点实验室开放课题,“万人计划”科技创新领军人才经费,生物样本由国家科技资源共享服务平台计划项目


Predicting male pattern baldness from DNA variants in a Eurasian population
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1.1)CAS Key Laboratory of Genomic and Precision Medicine, Beijing Institute of Genomics (China National Center for Bioinformation), Chinses Academy of Science, Life Sciences College, University of Chinese Academy of Sciences, Beijing 100101, China;2.2)National Engineering Laboratory for Forensic Science, Key Laboratory of Forensic Genetics of Ministry of Public Security, Beijing Engineering Research Center of Crime Scene Evidence Examination, Institute of Forensic Science, Ministry of Public Security, Beijing 100038, China;3.3)Criminal Investigation Department, Public Security Department of Hunan Province, Changsha 410001, China

Fund Project:

National Key R&D Program of China,Open Projects of National Engineering Laboratory for Forensic Science,The National Natural Science Foundation of China,Central Public-Interest Scientific Institution Basal Research Fund,The Open Project of Key Laboratory of Genomic and Precision Medicine, Chinese Academy of Sciences, National High-level personnel of special support program,Biological samples were provided by the National Science and Technological Resources Platform

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    摘要:

    男性型脱发(male pattern baldness,MPB)是一种雄激素依赖性的遗传性脱发疾病,对个人形象、心理产生较大的消极影响. 近期欧美人群中进行的大样本全基因组关联分析(genome wide association studies,GWAS)已报道大量与MPB相关的遗传易感性单核苷酸多态性(single nucleotide polymorphisms,SNPs)位点,但这些位点在东亚人群中的遗传效应尚不清楚. 本研究基于我国684个亚欧混合人群(Eurasian)样本,对在英国生物样本库(UK Biobank)205,327个欧洲男性GWAS分析发现的624个与MPB相关的SNPs进行人群异质性分析,基于多基因风险打分(polygenic risk scores,PRS)建立预测模型,并对预测因子数量与模型预测性能的关系进行了研究. 通过质控的467个SNPs中6.9%与MPB显著相关(P<0.05).结合年龄、体质指数(body mass index,BMI)和25个SNPs建立的线性回归和逻辑回归模型,效果较好(R2=28.9%,AUC=0.82). 年龄对模型效果影响较大(R2=22.9%,AUC=0.77),结合BMI及68个SNPs时AUC达到最大(约0.89). 本研究表明MPB在欧洲和东亚人群中存在较强的遗传异质性,选取SNPs子集能达到与全集相近的预测准确性,预测模型有助于东亚人群MPB遗传机制的理解及疾病的早期诊断和预防.

    Abstract:

    Male pattern baldness is the most common type of progressive hair loss, which has a considerable negative impact on personal image and mental health. Recently, several large sized genome-wide association studies (GWASs) in European and American populations have reported a large number of MPB-associated genetic susceptibility sites, but the genetic effects of these loci in East Asian populations remain unclear. This study was based on a sample of 684 Eurasian males in China, and conducted a population heterogeneity analysis on 624 MPB-related single nucleotide polymorphisms (SNPs) found in a large GWAS consisting of 205,327 European males in the UK Biobank. Polygenic risk scores (PRS) were used to build predictive models, and the relationship between the number of predictive factors and the predictive performance of the model was investigated. A total of 467 SNPs passed quality control, among which 6.9% showed nominally significant association with MPB (P <0.05). Linear and logistic models established by including the effects of age, body mass index (BMI), and 25 SNPs demonstrated fairly accurate prediction accuracy (R2 = 28.9%, AUC = 0.82). Age had the greatest impact on the model performance (R2 = 22.9%, AUC = 0.77), and the AUC reached the maximum when BMI and 68 SNPs were added cumulatively (about 0.89). This study indicates that MPB has strong genetic heterogeneity in European and East Asian populations. Selecting a subset of SNPs can achieve prediction accuracy close to that of the complete set. The prediction model constructed here may help understand the genetic mechanism, early diagnosis and prevention of MPB in East Asian populations.

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潘思宇,赵雯婷,冯锐,李琼,景晓溪,高行健,陈燕,李祎,陶现明,刘天资,李彩霞.基于DNA变异在亚欧混合人群中预测男性型脱发[J].生物化学与生物物理进展,2020,47(10):1069-1079

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历史
  • 收稿日期:2020-04-11
  • 最后修改日期:2020-06-22
  • 接受日期:2020-07-07
  • 在线发布日期: 2021-01-19
  • 出版日期: 2020-10-20