University of Groningen, University Medical Center Groningen, Department of Epidemiology, Groningen, the Netherlands; University of Groningen, University Medical Center Groningen, University Center for Psychiatry, Rob Giel Research Center, Groningen, the Netherlands.
University of Groningen, University Medical Center Groningen, Department of Epidemiology, Groningen, the Netherlands; Shahjalal University of Science and Technology, Department of Statistics, Sylhet, Bangladesh.
J Psychosom Res. 2020 May;132:109968. doi: 10.1016/j.jpsychores.2020.109968. Epub 2020 Feb 19.
Type 2 diabetes (T2D) is a common comorbidity in patients with schizophrenia (SCZ). The underlying pathophysiologic mechanisms are yet to be fully elucidated, although it can be argued that shared genes, environmental factors or their interaction effect are involved. This study investigated the association between polygenic risk score of SCZ (PRS) and glycated haemoglobin (HbA1c) while adjusting for polygenic risk score of T2D (PRS), and clinical and demographic covariables.
Genotype, clinical and demographic data of 1129 patients with non-affective psychosis were extracted from Genetic Risk and Outcome of Psychosis (GROUP) cohort study. The glycated haemoglobin (HbA1c) was the outcome. PRS was calculated using standard methods. Univariable and multivariable linear regression analyses were applied to estimate associations. Additionally, sensitivity analysis based on multiple imputation was done. After correction for multiple testing, a two-sided p-value ≤.003 was considered to discover evidence for an association.
Of 1129 patients, 75.8% were male with median age of 29 years. The mean (standard deviation) HbA1c level was 35.1 (5.9) mmol/mol. There was no evidence for an association between high HbA1c level and increased PRS (adjusted regression coefficient (aβ) = 0.69, standard error (SE) = 0.77, p-value = .37). On the other hand, there was evidence for an association between high HbA1c level and increased PRS (aβ = 0.93, SE = 0.32, p-value = .004), body mass index (aβ = 0.20, SE = 0.08, p-value = .01), diastolic blood pressure (aβ = 0.08, SE = 0.04, p-value = .03), late age of first psychosis onset (aβ = 0.19, SE = 0.05, p-value = .0004) and male gender (aβ = 1.58, SE = 0.81, p-value = .05). After multiple testing correction, there was evidence for an association between high HbA1c level and late age of first psychosis onset. Evidence for interaction effect between PRS and antipsychotics was not observed. The multiple imputation-based sensitivity analysis provided consistent results with complete case analysis.
Glycemic dysregulation in patients with SCZ was not associated with PRS. This suggests that the mechanisms of hyperglycemia or diabetes are at least partly independent from genetic predisposition to SCZ. Our findings show that the change in HbA1c level can be caused by at least in part due to PRS, late age of illness onset, male gender, and increased body mass index and diastolic blood pressure.
2 型糖尿病（T2D）是精神分裂症（SCZ）患者常见的合并症。尽管可以认为涉及共同的基因、环境因素或它们的相互作用效应，但潜在的病理生理机制尚未完全阐明。本研究调查了 SCZ 的多基因风险评分（PRS）与糖化血红蛋白（HbA1c）之间的关联，同时调整了 T2D 的多基因风险评分（PRS）和临床及人口统计学协变量。
从遗传风险和精神病结局（GROUP）队列研究中提取了 1129 名非情感性精神病患者的基因型、临床和人口统计学数据。糖化血红蛋白（HbA1c）为结果。使用标准方法计算 PRS。应用单变量和多变量线性回归分析来估计关联。此外，还进行了基于多重插补的敏感性分析。经过多次检验校正后，双侧 p 值≤.003 被认为发现了关联的证据。
在 1129 名患者中，75.8%为男性，中位年龄 29 岁。平均（标准差）HbA1c 水平为 35.1（5.9）mmol/mol。HbA1c 水平升高与 PRS 增加之间没有关联（调整后的回归系数（aβ）= 0.69，标准误差（SE）= 0.77，p 值=.37）。另一方面，HbA1c 水平升高与 PRS 增加之间存在关联（aβ= 0.93，SE= 0.32，p 值=.004），体重指数（aβ= 0.20，SE= 0.08，p 值=.01），舒张压（aβ= 0.08，SE= 0.04，p 值=.03），首发精神病的晚期年龄（aβ= 0.19，SE= 0.05，p 值=.0004）和男性性别（aβ= 1.58，SE= 0.81，p 值=.05）。经过多次检验校正后，HbA1c 水平升高与首发精神病的晚期年龄之间存在关联的证据。未观察到 PRS 和抗精神病药物之间存在交互作用效应的证据。基于多重插补的敏感性分析提供了与完整病例分析一致的结果。
SCZ 患者的血糖失调与 PRS 无关。这表明高血糖或糖尿病的机制至少部分独立于 SCZ 的遗传易感性。我们的研究结果表明，HbA1c 水平的变化至少部分归因于 PRS、疾病发病年龄晚、男性、体重指数增加和舒张压升高。
