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

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.

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.

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.

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.