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Weak Association Between the Glutamate Decarboxylase 1 Gene (GAD1) and Schizophrenia in Han Chinese Population

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机构： [1]Henan Mental Hospital, The Second Affiliated Hospital of Xinxiang Medical University, Xinxiang, China. [2]Henan Key Lab of Biological Psychiatry, Xinxiang Medical University, Xinxiang, China. [3]International Joint Research Laboratory for Psychiatry and Neuroscience of Henan, Xinxiang, China. [4]Key Laboratory of Animal Models and Human Disease Mechanisms of the Chinese Academy of Sciences and Yunnan Province, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, China. [5]Henan Province People's Hospital, Zhengzhou, China.

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Schizophrenia (SZ) is a complex psychiatric disorder with high heritability, and genetic components are thought to be pivotal risk factors for this illness. The glutamate decarboxylase 1 gene (GAD1) was hypothesized to be a candidate risk locus for SZ given its crucial role in the GABAergic neurotransmission system, and previous studies have examined the associations of single nucleotide polymorphisms (SNPs) spanning the GAD1 gene with SZ. However, inconsistent results were obtained. We hence examined the associations between GAD1 SNPs and SZ in two independent case-control samples of Han Chinese ancestry.Two Han Chinese SZ case-control samples, referred as the discovery sample and the replication sample, respectively, were recruited for the current study. The discovery sample comprised of 528 paranoid SZ cases (with age of first onset ≥ 18) and 528 healthy controls; the independent replication sample contained 1,256 early onset SZ cases (with age of first onset < 18) and 2,661 healthy controls. Logistic regression analysis was performed to examine the associations between GAD1 SNPs and SZ.Ten SNPs covering GAD1 gene were analyzed in the discovery sample, and two SNPs showed nominal associations with SZ (rs2241165, P = 0.0181, OR = 1.261; rs2241164, P = 0.0225, OR = 1.219). SNP rs2241164 was also nominally significant in the independent replication sample (P = 0.0462, OR = 1.110), and the significance became stronger in a subsequent meta-analysis combining both discovery and replication samples (P = 0.00398, OR = 1.138). Nevertheless, such association could not survive multiple corrections, although the effect size of rs2241164 was comparable with other SZ risk loci identified in genome-wide association studies (GWAS) in Han Chinese population. We also examined the associations between GAD1 SNPs and SZ in published datasets of SZ GWAS in East Asians and Europeans, and no significant associations were observed.We observed weak associations between GAD1 SNPs and risk of SZ in Han Chinese populations. Further analyses in larger Han Chinese samples with more detailed phenotyping are necessary to elucidate the genetic correlation between GAD1 SNPs and SZ.Copyright © 2021 Zhang, Li, Liu, Shao, Sun, Su, Song, Zhang, Ding, Lu, Liu, Yang, Li, Li and Lv.

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出版当年[2021]版：

大类 | 3 区医学

小类 | 3 区神经科学

最新[2023]版：

大类 | 3 区医学

小类 | 3 区神经科学

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第一作者机构： [1]Henan Mental Hospital, The Second Affiliated Hospital of Xinxiang Medical University, Xinxiang, China. [2]Henan Key Lab of Biological Psychiatry, Xinxiang Medical University, Xinxiang, China. [3]International Joint Research Laboratory for Psychiatry and Neuroscience of Henan, Xinxiang, China.

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通讯作者：

通讯机构： [1]Henan Mental Hospital, The Second Affiliated Hospital of Xinxiang Medical University, Xinxiang, China. [2]Henan Key Lab of Biological Psychiatry, Xinxiang Medical University, Xinxiang, China. [3]International Joint Research Laboratory for Psychiatry and Neuroscience of Henan, Xinxiang, China. [4]Key Laboratory of Animal Models and Human Disease Mechanisms of the Chinese Academy of Sciences and Yunnan Province, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, China. [5]Henan Province People's Hospital, Zhengzhou, China.

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