Liu Fan, Hamer Merel A, Heilmann Stefanie, Herold Christine, Moebus Susanne, Hofman Albert, Uitterlinden André G, Nöthen Markus M, van Duijn Cornelia M, Nijsten Tamar Ec, Kayser Manfred
Department of Genetic Identification, Erasmus MC University Medical Center Rotterdam, Rotterdam, The Netherlands.
Key Laboratory of Genomic and Precision Medicine, Beijing Institute of Genomics, Chinese Academy of Sciences, Beijing, China.
Eur J Hum Genet. 2016 Jun;24(6):895-902. doi: 10.1038/ejhg.2015.220. Epub 2015 Oct 28.
The global demand for products that effectively prevent the development of male-pattern baldness (MPB) has drastically increased. However, there is currently no established genetic model for the estimation of MPB risk. We conducted a prediction analysis using single-nucleotide polymorphisms (SNPs) identified from previous GWASs of MPB in a total of 2725 German and Dutch males. A logistic regression model considering the genotypes of 25 SNPs from 12 genomic loci demonstrates that early-onset MPB risk is predictable at an accuracy level of 0.74 when 14 SNPs were included in the model, and measured using the area under the receiver-operating characteristic curves (AUC). Considering age as an additional predictor, the model can predict normal MPB status in middle-aged and elderly individuals at a slightly lower accuracy (AUC 0.69-0.71) when 6-11 SNPs were used. A variance partitioning analysis suggests that 55.8% of early-onset MPB genetic liability can be explained by common autosomal SNPs and 23.3% by X-chromosome SNPs. For normal MPB status in elderly individuals, the proportion of explainable variance is lower (42.4% for autosomal and 9.8% for X-chromosome SNPs). The gap between GWAS findings and the variance partitioning results could be explained by a large body of common DNA variants with small effects that will likely be identified in GWAS of increased sample sizes. Although the accuracy obtained here has not reached a clinically desired level, our model was highly informative for up to 19% of Europeans, thus may assist decision making on early MPB intervention actions and in forensic investigations.
全球对有效预防男性型秃发(MPB)产品的需求急剧增加。然而,目前尚无用于评估MPB风险的既定遗传模型。我们对总共2725名德国和荷兰男性中先前MPB全基因组关联研究(GWAS)鉴定出的单核苷酸多态性(SNP)进行了预测分析。一个考虑来自12个基因组位点的25个SNP基因型的逻辑回归模型表明,当模型中纳入14个SNP时,早发性MPB风险的预测准确率可达0.74,采用受试者工作特征曲线下面积(AUC)进行测量。将年龄作为额外的预测因素,当使用6 - 11个SNP时,该模型可以以稍低的准确率(AUC 0.69 - 0.71)预测中年和老年个体的正常MPB状态。方差划分分析表明,55.8%的早发性MPB遗传易感性可由常见常染色体SNP解释,23.3%可由X染色体SNP解释。对于老年个体的正常MPB状态,可解释变异的比例较低(常染色体为42.4%,X染色体SNP为9.8%)。GWAS结果与方差划分结果之间的差距可以用大量效应较小的常见DNA变异来解释,这些变异可能会在样本量增加的GWAS中被鉴定出来。尽管这里获得的准确率尚未达到临床期望水平,但我们的模型对高达19%的欧洲人具有高度信息性,因此可能有助于在早期MPB干预行动决策和法医调查中提供帮助。