title: Association of ARHGAP18 polymorphisms with schizophrenia in the Chinese-Han population.
abstract: Numerous developmental genes have been linked to schizophrenia (SZ) by case-control and genome-wide association studies, suggesting that neurodevelopmental disturbances are major pathogenic mechanisms. However, no neurodevelopmental deficit has been definitively linked to SZ occurrence, likely due to disease heterogeneity and the differential effects of various gene variants across ethnicities. Hence, it is critical to examine linkages in specific ethnic populations, such as Han Chinese. The newly identified RhoGAP ARHGAP18 is likely involved in neurodevelopment through regulation of RhoA/C. Here we describe four single nucleotide polymorphisms (SNPs) in ARHGAP18 associated with SZ across a cohort of >2000 cases and controls from the Han population. Two SNPs, rs7758025 and rs9483050, displayed significant differences between case and control groups both in genotype (P = 0.0002 and P = 7.54×10-6) and allelic frequencies (P = 4.36×10-5 and P = 5.98×10-7), respectively. The AG haplotype in rs7758025-rs9385502 was strongly associated with the occurrence of SZ (P = 0.0012, OR = 0.67, 95% CI = 0.48-0.93), an association that still held following a 1000-times random permutation test (P = 0.022). In an independently collected validation cohort, rs9483050 was the SNP most strongly associated with SZ. In addition, the allelic frequencies of rs12197901 remained associated with SZ in the combined cohort (P = 0.021), although not in the validation cohort alone (P = 0.251). Collectively, our data suggest the ARHGAP18 may confer vulnerability to SZ in the Chinese Han population, providing additional evidence for the involvement of neurodevelopmental dysfunction in the pathogenesis of schizophrenia.
authors.affiliation: College of Life Science and Technology, Xinxiang Medical University, Xinxiang, China.|Henan Key Lab of Biological Psychiatry, Xinxiang Medical University, Xinxiang, China.
authors.forename: Weiyun
authors.identifier: http://orcid.org/0000-0001-8668-1051
authors.initials: W
authors.lastname: Guo
authors.affiliation: Henan Key Lab of Biological Psychiatry, Xinxiang Medical University, Xinxiang, China.|Department of Psychiatry, Henan Mental Hospital, The Second Affiliated Hospital of Xinxiang Medical University, Xinxiang, China.
authors.forename: Yaqi
authors.initials: Y
authors.lastname: Cai
authors.affiliation: Henan Key Lab of Biological Psychiatry, Xinxiang Medical University, Xinxiang, China.|Department of Psychiatry, Henan Mental Hospital, The Second Affiliated Hospital of Xinxiang Medical University, Xinxiang, China.|Department of Psychology, Xinxiang Medical University, Xinxiang, China.
authors.forename: Hongxing
authors.initials: H
authors.lastname: Zhang
authors.affiliation: Henan Key Lab of Biological Psychiatry, Xinxiang Medical University, Xinxiang, China.|Department of Psychiatry, Henan Mental Hospital, The Second Affiliated Hospital of Xinxiang Medical University, Xinxiang, China.
authors.forename: Yongfeng
authors.initials: Y
authors.lastname: Yang
authors.affiliation: Henan Key Lab of Biological Psychiatry, Xinxiang Medical University, Xinxiang, China.|Department of Psychiatry, Henan Mental Hospital, The Second Affiliated Hospital of Xinxiang Medical University, Xinxiang, China.
authors.forename: Ge
authors.initials: G
authors.lastname: Yang
authors.affiliation: Henan Key Lab of Biological Psychiatry, Xinxiang Medical University, Xinxiang, China.|Department of Psychiatry, Henan Mental Hospital, The Second Affiliated Hospital of Xinxiang Medical University, Xinxiang, China.
authors.forename: Xiujuan
authors.initials: X
authors.lastname: Wang
authors.affiliation: Department of Psychiatry, Henan Mental Hospital, The Second Affiliated Hospital of Xinxiang Medical University, Xinxiang, China.
authors.forename: Jingyuan
authors.initials: J
authors.lastname: Zhao
authors.affiliation: College of Life Science and Technology, Xinxiang Medical University, Xinxiang, China.|Henan Key Lab of Biological Psychiatry, Xinxiang Medical University, Xinxiang, China.|Institute of Anatomy I, Friedrich Schiller University Jena, Jena, Germany.
authors.forename: Juntang
authors.initials: J
authors.lastname: Lin
authors.affiliation: Institute of Anatomy I, Friedrich Schiller University Jena, Jena, Germany.|Department of Psychology, Xinxiang Medical University, Xinxiang, China.
authors.forename: Jinfu
authors.initials: J
authors.lastname: Zhu
authors.affiliation: Henan Key Lab of Biological Psychiatry, Xinxiang Medical University, Xinxiang, China.|Department of Psychiatry, Henan Mental Hospital, The Second Affiliated Hospital of Xinxiang Medical University, Xinxiang, China.
authors.forename: Wenqiang
authors.initials: W
authors.lastname: Li
authors.affiliation: Henan Key Lab of Biological Psychiatry, Xinxiang Medical University, Xinxiang, China.|Department of Psychiatry, Henan Mental Hospital, The Second Affiliated Hospital of Xinxiang Medical University, Xinxiang, China.
authors.forename: Luxian
authors.initials: L
authors.lastname: Lv
mesh_terms: D000328:Adult; D016022:Case-Control Studies; D002681:China; D015331:Cohort Studies; D005006:Ethnicity / Q000235:genetics*; D005260:Female; D020690:GTPase-Activating Proteins / Q000235:genetics*; D006801:Humans; D008297:Male; D020641:Polymorphism, Single Nucleotide; D012559:Schizophrenia / Q000235:genetics*; D055815:Young Adult
chemical_list: C542464:ARHGAP18 protein, human; D020690:GTPase-Activating Proteins