CAS Key Laboratory of Genomic and Precision Medicine, Beijing Institute of Genomics, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Beijing, China.
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, China.
Int J Legal Med. 2019 Nov;133(6):1667-1679. doi: 10.1007/s00414-019-02039-8. Epub 2019 Apr 12.
Accurate genomic profiling for adult height is of high practical relevance in forensics genetics. Adult height is a classical reference trait in the field of human complex trait genetics characterized by highly polygenic nature and relatively high heritability. A meta-analysis of genome-wide association studies by the Genetic Investigation of Anthropocentric Traits (GIANT) consortium has identified 697 DNA variants associated with adult height in Europeans; however, whether these variants will still be informative in non-Europeans is still in question. The present study investigated the predictive power of these 697 height-associated SNPs in 687 Uyghurs of European-Asian admixed origin. Among all GIANT SNPs, 11% showed nominally significant association (6.78 × 10 < p < 0.05) with adult height in the Uyghur population and among the significant SNPs 77% of allele effects were in the same direction as those in Europeans reported in the GIANT study. Fitting linear and logistic models using a polygenic score consisting of all GIANT SNPs resulted in an 80-20 cross-validated mean R of 10.08% (95% CI 3.16-18.40%) for quantitative height prediction and a mean AUC value of 0.65 (95% CI 0.57-0.72%) for qualitative "above average" prediction. Fine-tuning the SNP set using their association p values considerably improved the prediction results (number of SNPs = 62, R = 15.59%, 95% CI 6.80-25.71%; AUC = 0.70, 95% CI 62-0.77) in the Uyghurs. Overall, our findings demonstrate substantial differences between the European and Asian populations in the genetics of adult height, emphasizing the importance of population heterogeneity underlying the genetic architecture of adult height.
成人身高的准确基因组分析在法医学遗传学中具有很高的实际意义。成人身高是人类复杂特征遗传学领域的经典参考特征，具有高度多基因性质和相对较高的遗传性。遗传人类特征综合分析联盟（GIANT）的全基因组关联研究荟萃分析已经确定了 697 个与欧洲人成人身高相关的 DNA 变体；然而，这些变体在非欧洲人中是否仍然具有信息性仍存在疑问。本研究调查了这 697 个与身高相关的 SNP 在 687 名欧亚混血的维吾尔族中的预测能力。在所有 GIANT SNP 中，11%在维吾尔族人群中与成人身高呈名义显著相关（6.78×10-8<p<0.05），并且在显著 SNP 中，77%的等位基因效应与 GIANT 研究中报道的欧洲人一致。使用由所有 GIANT SNP 组成的多基因评分拟合线性和逻辑模型，导致定量身高预测的 80-20 交叉验证平均 R 值为 10.08%（95%CI 3.16-18.40%），定性“高于平均”预测的平均 AUC 值为 0.65（95%CI 0.57-0.72%）。使用它们的关联 p 值对 SNP 集进行微调，大大改善了预测结果（SNP 数量=62，R=15.59%，95%CI 6.80-25.71%；AUC=0.70，95%CI 62-0.77%）。总体而言，我们的研究结果表明，欧洲人和亚洲人群在成人身高的遗传学方面存在很大差异，强调了人口异质性在成人身高遗传结构中的重要性。
