Variants of Th17 pathway-related genes influence brain morphometric changes and the risk of schizophrenia through epistatic interactions.

IF 1.5 4区医学 Q4 GENETICS & HEREDITY Psychiatric Genetics Pub Date : 2022-08-01 Epub Date: 2022-03-31 DOI:10.1097/YPG.0000000000000315

Manjula Subbanna, Venkataram Shivakumar, Gaurav Bhalerao, Shivarama Varambally, Ganesan Venkatasubramanian, Monojit Debnath

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Abstract

Objective: T helper 17 (Th17) pathway has been reported to be abnormal in schizophrenia; however, it is not known whether variation within genes of this pathway has any impact on schizophrenia. Herein, the impact of genetic variations and gene-gene interactions of Th17 pathway-related genes on the risk, psychopathology, and brain volume was examined in schizophrenia patients.

Methods: Functional polymorphisms within interleukin 6 ( IL6 )(rs1800795 and rs1800797), IL10 (rs1800872 and rs1800896), IL17A (rs2275913 and rs8193036), IL22 (rs2227484 and rs2227485), IL23R (rs1884444), and IL27 (rs153109 and rs181206) genes were studied in 224 schizophrenia patients and 226 healthy controls. These variants were correlated with the brain morphometry, analyzed using MRI in a subset of patients ( n = 117) and controls ( n = 137).

Results: Patients carrying CC genotype of rs2227484 of IL22 gene had significantly higher apathy total score [ F (1,183) = 5.60; P = 0.019; partial ɳ 2 = 0.030]. Significant epistatic interactions between IL6 (rs1800797) and IL17A (rs2275913) genes were observed in schizophrenia patients. GG genotype of rs2275913 of IL17A gene was associated with reduced right middle occipital gyrus volume in schizophrenia patients ( T = 4.56; P < 0.001).

Conclusion: Interactions between genes of Th17 pathway impact the risk for schizophrenia. The variants of Th17 pathway-related genes seem to have a determining effect on psychopathology and brain morphometric changes in schizophrenia.

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Th17通路相关基因的变体通过上位性相互作用影响大脑形态计量学变化和精神分裂症的风险。

目的：据报道，精神分裂症患者Th17通路异常；然而，目前尚不清楚该途径基因内的变异是否对精神分裂症有任何影响。在此，研究了精神分裂症患者Th17通路相关基因的遗传变异和基因-基因相互作用对风险、精神病理学和脑容量的影响。方法：对224名精神分裂症患者和226名健康对照者的白细胞介素6（IL6）（rs1800795和rs1800797）、IL10（rs1800872和rs1800896）、IL17A（rs2275913和rs8193036）、IL-22（rs2227484和rs2227485）、IL23R（rs1884444）和IL27（rs153109和rs181206）基因的功能多态性进行研究。这些变体与大脑形态计量学相关，结果：携带IL22基因rs2227484 CC基因型的患者冷漠总分显著高于对照组（n=137）[F（1183）=5.60；P=0.019；partialɳ2=0.030]。在精神分裂症患者中观察到IL6（rs1800797）和IL17A（rs2275913）基因之间的显著上位相互作用。IL17A基因rs2275913 GG基因型与精神分裂症患者右侧枕中回体积减少有关（T=4.56；P<0.001）。Th17通路相关基因的变异似乎对精神分裂症的精神病理学和大脑形态计量学变化具有决定性影响。

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来源期刊

Psychiatric Genetics 医学-神经科学

CiteScore

2.30

自引率

0.00%

发文量

审稿时长

3 months

期刊介绍： The journal aims to publish papers which bring together clinical observations, psychological and behavioural abnormalities and genetic data. All papers are fully refereed. Psychiatric Genetics is also a forum for reporting new approaches to genetic research in psychiatry and neurology utilizing novel techniques or methodologies. Psychiatric Genetics publishes original Research Reports dealing with inherited factors involved in psychiatric and neurological disorders. This encompasses gene localization and chromosome markers, changes in neuronal gene expression related to psychiatric disease, linkage genetics analyses, family, twin and adoption studies, and genetically based animal models of neuropsychiatric disease. The journal covers areas such as molecular neurobiology and molecular genetics relevant to mental illness. Reviews of the literature and Commentaries in areas of current interest will be considered for publication. Reviews and Commentaries in areas outside psychiatric genetics, but of interest and importance to Psychiatric Genetics, will also be considered. Psychiatric Genetics also publishes Book Reviews, Brief Reports and Conference Reports.