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Background <p>Long-term use of second-generation antipsychotics (SGAs) increases the risk of metabolic syndrome (MS) in patients with schizophrenia (SCZ). Using susceptibility loci identified by European Genome-Wide Association Study (GWAS) as entry points, we conducted a case–control study to verify their association with antipsychotic-induced MS in Chinese Han SCZ patients.</p> Methods <p>Clinical and metabolic data were collected from 528 chronically SCZ patients who had been treated with SGAs for ≥ 12 months. Patients were divided into MS (<i>n</i> = 232) and non-MS (<i>n</i> = 296) groups. Forty tag single-nucleotide polymorphisms (SNPs) selected from European GWAS data were genotyped; inter-group comparisons and risk analyses for MS-related factors were performed.</p> Results <p>Compared with the non-MS group, the MS group exhibited significantly elevated waist circumference, systolic blood pressure (SBP), diastolic blood pressure (DBP), triglycerides (TG), fasting plasma glucose (FPG), and body-mass index (BMI), alongside significantly reduced age and high-density lipoprotein cholesterol (HDL-C) levels (all <i>P</i> &lt; 0.05). Allele-based analysis revealed that the G allele of G-protein–coupled receptor 98 (<i>GPR98</i>) rs1967256 was more prevalent in MS patients (χ² = 4.049, <i>P</i> = 0.046), whereas the T allele of Tudor domain-containing protein 15 / Long intergenic non-protein coding RNA 1822 (<i>TDRD15</i>/<i>LINC01822</i>) rs1117324 showed reduced frequency (χ² = 6.639, <i>P</i> = 0.011). Genotype analysis further indicated an over-representation of the rs1117324 T/T genotype in the MS group (χ² = 10.833, <i>P</i> = 0.004). Multivariate logistic regression demonstrated that older age at onset, lower BMI and rs1117324 C/T genotype (compared to T/T) were protective factors, while rs1117324 C/C genotype was risk factor for hyperglycaemia. In addition, male sex, higher BMI and rs1967256 C/C genotype (compared to GG) were identified as risk factors for low HDL-C.</p> Conclusions <p>Among the 40 MS susceptibility loci previously identified by European GWAS, we validated two loci—<i>GPR98</i> rs1967256 and <i>TDRD15</i>/<i>LINC01822</i> rs1117324—as being significantly associated with antipsychotic-induced MS in Chinese Han patients with SCZ.</p>

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Cross-population validation of European GWAS loci for metabolic syndrome in Chinese schizophrenia

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年5月6日

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  • Yangyang You,
  • Ning Qiao,
  • Yao Chen,
  • Zhou Wang,
  • Lirong Zhuang,
  • Xinyu Fang,
  • Xiaowei Tang,
  • Xiangrong Zhang

摘要

Background

Long-term use of second-generation antipsychotics (SGAs) increases the risk of metabolic syndrome (MS) in patients with schizophrenia (SCZ). Using susceptibility loci identified by European Genome-Wide Association Study (GWAS) as entry points, we conducted a case–control study to verify their association with antipsychotic-induced MS in Chinese Han SCZ patients.

Methods

Clinical and metabolic data were collected from 528 chronically SCZ patients who had been treated with SGAs for ≥ 12 months. Patients were divided into MS (n = 232) and non-MS (n = 296) groups. Forty tag single-nucleotide polymorphisms (SNPs) selected from European GWAS data were genotyped; inter-group comparisons and risk analyses for MS-related factors were performed.

Results

Compared with the non-MS group, the MS group exhibited significantly elevated waist circumference, systolic blood pressure (SBP), diastolic blood pressure (DBP), triglycerides (TG), fasting plasma glucose (FPG), and body-mass index (BMI), alongside significantly reduced age and high-density lipoprotein cholesterol (HDL-C) levels (all P < 0.05). Allele-based analysis revealed that the G allele of G-protein–coupled receptor 98 (GPR98) rs1967256 was more prevalent in MS patients (χ² = 4.049, P = 0.046), whereas the T allele of Tudor domain-containing protein 15 / Long intergenic non-protein coding RNA 1822 (TDRD15/LINC01822) rs1117324 showed reduced frequency (χ² = 6.639, P = 0.011). Genotype analysis further indicated an over-representation of the rs1117324 T/T genotype in the MS group (χ² = 10.833, P = 0.004). Multivariate logistic regression demonstrated that older age at onset, lower BMI and rs1117324 C/T genotype (compared to T/T) were protective factors, while rs1117324 C/C genotype was risk factor for hyperglycaemia. In addition, male sex, higher BMI and rs1967256 C/C genotype (compared to GG) were identified as risk factors for low HDL-C.

Conclusions

Among the 40 MS susceptibility loci previously identified by European GWAS, we validated two loci—GPR98 rs1967256 and TDRD15/LINC01822 rs1117324—as being significantly associated with antipsychotic-induced MS in Chinese Han patients with SCZ.