基于DNA变异在亚欧混合人群中预测男性型脱发

Predicting Male Pattern Baldness From DNA Variants in a Eurasian Population

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)205327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(R^2=28.9%,AUC=0.82).年龄对模型效果影响较大(R^2=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.

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 205327 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 of467 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(R^2=28.9%,AUC=0.82).Age had the greatest impact on the model performance(R^2=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.