精神分裂症(SCZ)患者经常表现出代谢综合征(MetS)的高风险,这可能会导致更糟糕的临床结果。尽管这两种表型是遗传连锁的,对它们共同的遗传决定因素知之甚少。这里,我们调查了SCZ和MetS是否具有遗传风险因素。为了检查这两种疾病之间的遗传重叠,我们通过整合基因组中SCZ(n=320,404)和MetS(n=291,107)的GWAS数据,应用了全面的遗传重叠分析,遗传变异,和基因水平。在基因组水平,我们通过LDSC(rg=-0.09,P=1×10-4)和GNOVA(rho=-0.04,P=1.39×10-8)分析观察到SCZ和MetS之间的多基因重叠。在SNP级别,我们进行了联合FDR(conjFDR)分析,以鉴定同时与两种表型相关的遗传变异.基于conjFDR<0.05,我们确定了SCZ和MetS之间共有的22个基因座。在基因层面,我们进一步证明SCZ和MetS推断的基因表达在49个GTEx组织中重叠,并强调PCCB和KCTD13基因是遗传关联的推定介质.总的来说,这些发现为SCZ和MetS之间的关联提供了新的启示,并可能增强我们对两种疾病之间重叠的高合并症和遗传过程的认识。
Patients with schizophrenia (SCZ) frequently exhibit an elevated risk of metabolic syndrome (MetS), which may lead to a worse clinical outcome. Even though these two phenotypes are genetically linked, little is known about their shared genetic determinants. Here, we investigated whether SCZ and MetS share genetic risk factors. To examine the genetic overlap between the two disorders, we applied a comprehensive genetic overlap analysis by integrating GWAS data for SCZ (n = 320,404) and MetS (n = 291,107) at the genome, genetic variants, and gene levels. At the genome level, we observed polygenic overlap between SCZ and MetS by utilizing LDSC (rg=-0.09, P = 1 × 10-4) and GNOVA (rho=-0.04, P = 1.39 × 10-8) analysis. At the SNP level, we performed conjunctional FDR (conjFDR) analysis to identify genetic variants simultaneously associated with two phenotypes. Based on conjFDR < 0.05, we identified 22 loci shared between SCZ and MetS. At the gene level, we further demonstrated that SCZ- and MetS-inferred gene expression overlapped across 49 GTEx tissues and highlighted the PCCB and KCTD13 genes as putative mediators of the genetic association. Overall, these findings shed novel light on the association between SCZ and MetS, and potentially enhance our knowledge of the high comorbidity and genetic processes that overlap between the two disorders.