Predicting adult height from DNA variants in a European-Asian admixed population.
Xiaoxi Jing, Yanan Sun, Wenting Zhao, Xingjian Gao, Mi Ma, Fan Liu, Caixia Li
Author Information
Xiaoxi Jing: CAS Key Laboratory of Genomic and Precision Medicine, Beijing Institute of Genomics, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Beijing, China.
Yanan Sun: 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.
Wenting Zhao: 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.
Xingjian Gao: CAS Key Laboratory of Genomic and Precision Medicine, Beijing Institute of Genomics, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Beijing, China.
Mi Ma: 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.
Fan Liu: CAS Key Laboratory of Genomic and Precision Medicine, Beijing Institute of Genomics, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Beijing, China. liufan@big.ac.cn.
Caixia Li: 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. licaixia@tsinghua.org.cn.
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.
