Asian-European differentiation of schizophrenia-associated genes driven by admixture and natural selection
Sihan Chen,
Die Tang,
Lian Deng,
Shuhua Xu
Affiliations
Sihan Chen
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
Die Tang
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
Lian Deng
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; Corresponding author
Shuhua Xu
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; Corresponding author
Summary: 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 SLC5A10-rs1624825, and a damaging variant TSPAN18-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 LTN1-rs57646126-A in Asians, and a non-risk allele ZSWIM6-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.
