Abstract:
Background: Response to antipsychotics is subject to a wide interindividual variability, due to genetic and non-genetic factors. Several single nucleotide polymorphisms (SNPs) have been associated with response to antipsychotics in genome-wide association studies (GWAS). Polygenic risk scores (PRS) are a powerful tool to aggregate into a single measure the small effects of multiple risk alleles. Materials and methods: We studied the association between a PRS composed of SNPs associated with response to antipsychotics in GWAS studies (PRSresponse) in a real-world sample of patients (N = 460) with different diagnoses (schizophrenia spectrum, bipolar, depressive, neurocognitive, substance use disorders and miscellaneous). Two other PRSs composed of SNPs previously associated with risk of schizophrenia (PRSschizophrenia1 and PRSschizophrenia2) were also tested for their association with response to treatment. Results: PRSresponse was significantly associated with response to antipsychotics considering the whole cohort (OR = 1.14, CI = 1.03-1.26, p = 0.010), the subgroup of patients with schizophrenia, schizoaffective disorder or bipolar disorder (OR = 1.18, CI = 1.02-1.37, p = 0.022, N = 235), with schizophrenia or schizoaffective disorder (OR = 1.24, CI = 1.04-1.47, p = 0.01, N = 176) and with schizophrenia (OR = 1.27, CI = 1.04-1.55, p = 0.01, N = 149). Sensitivity and specificity were sub-optimal (schizophrenia 62%, 61%; schizophrenia spectrum 56%, 55%; schizophrenia spectrum plus bipolar disorder 60%, 56%; all patients 63%, 58%, respectively). PRSschizophrenia1 and PRSschizophrenia2 were not significantly associated with response to treatment. Conclusion: PRSresponse defined from GWAS studies is significantly associated with response to antipsychotics in a real-world cohort; however, the results of the sensitivity-specificity analysis preclude its use as a predictive tool in clinical practice.
摘要:
背景:对抗精神病药物的反应受到广泛的个体差异的影响,由于遗传和非遗传因素。在全基因组关联研究(GWAS)中,几种单核苷酸多态性(SNP)与抗精神病药的反应有关。多基因风险评分(PRS)是一种强大的工具,可以将多个风险等位基因的小影响汇总到单个度量中。材料和方法:我们研究了由SNP组成的PRS与GWAS研究(PRS反应)中对抗精神病药的反应之间的关联,该研究是在具有不同诊断(精神分裂症谱,双极,抑郁,神经认知,物质使用障碍和其他)。还测试了另外两个由先前与精神分裂症风险相关的SNP组成的PRS(PRS精神分裂症ia1和PRS精神分裂症ia2)与治疗反应的相关性。结果:考虑到整个队列,PRS反应与抗精神病药物的反应显着相关(OR=1.14,CI=1.03-1.26,p=0.010),精神分裂症患者的亚组,分裂情感障碍或双相情感障碍(OR=1.18,CI=1.02-1.37,p=0.022,N=235),精神分裂症或分裂情感障碍(OR=1.24,CI=1.04-1.47,p=0.01,N=176)和精神分裂症(OR=1.27,CI=1.04-1.55,p=0.01,N=149)。敏感性和特异性次优(精神分裂症62%,61%;精神分裂症谱56%,55%;精神分裂症谱加躁郁症60%,56%;所有患者63%,58%,分别)。PRS精神分裂症ia1和PRS精神分裂症ia2与治疗反应没有显着相关。结论:在真实世界队列中,GWAS研究定义的PRS反应与抗精神病药物的反应显着相关;然而,敏感性-特异性分析的结果排除了其在临床实践中作为预测工具的用途.