Mental Health Centre Copenhagen, University of Copenhagen, Faculty of Health Sciences, Copenhagen; National Centre for Register-Based Research, Aarhus University, Aarhus; The Lundbeck Foundation Initiative for Integrative Psychiatric Research iPSYCH, Copenhagen.
National Centre for Register-Based Research, Aarhus University, Aarhus; The Lundbeck Foundation Initiative for Integrative Psychiatric Research iPSYCH, Copenhagen.
Biol Psychiatry. 2016 Oct 15;80(8):609-16. doi: 10.1016/j.biopsych.2016.04.008. Epub 2016 Apr 19.
Several studies have suggested an important role of infections in the etiology of schizophrenia; however, shared genetic liability toward infections and schizophrenia could influence the association. We therefore investigated the possible effect of polygenic risk scores (PRSs) for schizophrenia on the association between infections and the risk of schizophrenia.
We conducted a nested case-control study on a Danish population-based sample born after 1981 comprising of 1692 cases diagnosed with schizophrenia between 1994 and 2008 and 1724 matched controls. All individuals were linked utilizing nationwide population-based registers with virtually complete registration of all hospital contacts for infections. PRSs were calculated using discovery effect size estimates weights from an independent meta-analysis (34,600 cases and 45,968 control individuals).
A prior hospital contact with infection had occurred in 41% of the individuals with schizophrenia and increased the incidence rate ratio (IRR) of schizophrenia by 1.43 (95% confidence interval [CI] = 1.22-1.67). Adding PRS, which was robustly associated with schizophrenia (by an IRR of 1.46 [95% CI = 1.34-1.60] per standard deviation of the score), did not alter the association with infections and the increased risk of schizophrenia remained (IRR = 1.41; 95% CI = 1.20-1.66). Furthermore, there were no interactions between PRS and infections on the risk of developing schizophrenia (p = .554). Neither did PRS affect the risk of acquiring infections among patients with schizophrenia (odds ratio = 1.00; 95% CI = 0.89-1.12) nor among controls (odds ratio = 1.09; 95% CI: 0.96-1.24).
PRS and a history of infections have independent effects on the risk for schizophrenia, and the common genetic risk measured by PRS did not account for the association with infection in this sample.
多项研究表明，感染在精神分裂症的病因学中起着重要作用；然而，感染和精神分裂症的共同遗传易感性可能会影响这种关联。因此，我们研究了精神分裂症多基因风险评分（PRS）对感染与精神分裂症风险之间关联的可能影响。
我们对丹麦一个 1981 年后出生的基于人群的样本进行了一项嵌套病例对照研究，该样本包括 1994 年至 2008 年间诊断出的 1692 例精神分裂症病例和 1724 例匹配对照。所有个体都利用全国性基于人群的登记册进行了链接，这些登记册几乎完整地记录了所有感染的医院接触情况。PRS 是使用独立荟萃分析（34600 例病例和 45968 例对照个体）的发现效应大小估计权重计算的。
41%的精神分裂症患者曾有过感染的医院接触史，使精神分裂症的发病率比值（IRR）增加了 1.43（95%置信区间[CI]为 1.22-1.67）。加入 PRS 后，其与精神分裂症的关联更为稳健（每标准分的 IRR 为 1.46[95%CI=1.34-1.60]），但并未改变与感染的关联，精神分裂症的发病风险仍然增加（IRR=1.41；95%CI=1.20-1.66）。此外，PRS 与感染之间在发展为精神分裂症的风险上没有交互作用（p=0.554）。PRS 也没有影响精神分裂症患者感染的风险（比值比=1.00；95%CI=0.89-1.12）或对照者的感染风险（比值比=1.09；95%CI：0.96-1.24）。
PRS 和感染史对精神分裂症的发病风险有独立的影响，而 PRS 所衡量的共同遗传风险并不能解释本样本中与感染的关联。
