Chen Sihan, Tang Die, Deng Lian, Xu Shuhua
State Key Laboratory of Genetic Engineering, Human Phenome Institute, Zhangjiang Fudan International Innovation Center, Center for Evolutionary Biology, School of Life Sciences, Department of Liver Surgery and Transplantation Liver Cancer Institute, Zhongshan Hospital, Fudan University, Shanghai 200032, China.
Ministry of Education Key Laboratory of Contemporary Anthropology, School of Life Sciences, Fudan University, Shanghai 200438, China.
iScience. 2024 Mar 26;27(5):109560. doi: 10.1016/j.isci.2024.109560. eCollection 2024 May 17.
The European-centered genome-wide association studies of schizophrenia (SCZ) may not be well applied to non-European populations. We analyzed 1,592 reported SCZ-associated genes using the public genome data and found an overall higher Asian-European differentiation on the SCZ-associated variants than at the genome-wide level. Notable examples included 15 missense variants, a regulatory variant -rs1624825, and a damaging variant -rs1001292. Independent local adaptations in recent 25,000 years, after the Asian-European divergence, could have contributed to such genetic differentiation, as were identified at a missense mutation -rs57646126-A in Asians, and a non-risk allele -rs72761442-G in Europeans. Altai-Neanderthal-derived alleles may have opposite effects on SCZ susceptibility between ancestries. Furthermore, adaptive introgression was detected on the non-risk haplotype at 1q21.2 in Europeans, while in Asians it was observed on the SCZ risk haplotype at 3p21.31 which is also potentially ultra-violet protective. This study emphasizes the importance of including more representative Asian samples in future SCZ studies.
以欧洲为中心的精神分裂症（SCZ）全基因组关联研究可能不适用于非欧洲人群。我们使用公共基因组数据分析了1592个已报道的与SCZ相关的基因，发现与SCZ相关的变异在亚洲人和欧洲人之间的分化总体上高于全基因组水平。显著的例子包括15个错义变异、一个调控变异——rs1624825，以及一个有害变异——rs1001292。在亚洲人和欧洲人分化后的近25000年里，独立的局部适应性可能导致了这种遗传分化，如在亚洲人身上发现的一个错义突变——rs57646126 - A，以及在欧洲人身上发现的一个非风险等位基因——rs72761442 - G。阿尔泰尼安德特人衍生的等位基因可能对不同祖先的SCZ易感性有相反的影响。此外，在欧洲人1q21.2的非风险单倍型上检测到适应性基因渗入，而在亚洲人身上，在3p21.31的SCZ风险单倍型上也观察到了适应性基因渗入，该单倍型也可能具有紫外线保护作用。这项研究强调了在未来的SCZ研究中纳入更具代表性的亚洲样本的重要性。
