Influence of Polygenic Risk Scores on the Association Between Infections and Schizophrenia

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• 作者：Michael E. Benros^a ; ^b ; ^c ; ^{Benros@dadlnet.dk" class="auth_mail" title="E-mail the corresponding author} ; Betina B. Trabjerg^b ; ^c ; Sandra Meier^b ; ^c ; Manuel Mattheisen^c ; ^e ; Preben B. Mortensen^b ; ^c ; Ole Mors^c ; ^f ; Anders D. Bø ; rglum^c ; ^e ; David M. Hougaard^g ; Bent Nø ; rgaard-Pedersen^g ; Merete Nordentoft^c ; Esben Agerbo^b ; ^c ; ^d
• 关键词：Epidemiology ; Genetics ; Infections ; Polygenic risk score ; Register-based ; Schizophrenia
• 刊名：Biological Psychiatry
• 出版年：2016
• 出版时间：15 October 2016
• 年：2016
• 卷：80
• 期：8
• 页码：609-616
• 全文大小：338 K

文摘

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.

Methods

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).

Results

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).

Conclusions

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.