Multiple genome‐wide association studies of schizophrenia have reported associations between genetic variants within the MHC region and disease risk, an association that has been partially accounted for by alleles of the complement component 4 (C4) gene. Following on previous findings of association between both C4 and other complement‐related variants and memory function, we tested the hypothesis that polygenic scores calculated based on identified schizophrenia risk alleles within the “complement” system would be broadly associated with memory function and associated brain structure. We tested this using a polygenic risk score (PRS) calculated for complement genes, but excluding C4 variants. Higher complement‐based PRS scores were observed to be associated with lower memory scores for the sample as a whole (N = 620, F change = 8.25; p = .004). A significant association between higher PRS and lower hippocampal volume was also observed (N = 216, R² change = 0.016, p = .015). However, after correcting for further testing of association with the more general indices of cortical thickness, surface area or total brain volume, none of which were associated with complement, the association with hippocampal volume became non‐significant. A post‐hoc analysis of hippocampal subfields suggested an association between complement PRS and several hippocampal subfields, findings that appeared to be particularly driven by the patient sample. In conclusion, our study yielded suggestive evidence of association between complement‐based schizophrenia PRS and variation in memory function and hippocampal volume.

中文翻译：

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补体基因组多基因风险评分对精神病患者和健康对照者脑容量和皮质测量的影响。

精神分裂症的全基因组关联研究表明，MHC区域内的遗传变异与疾病风险之间存在关联，该关联已由补体成分4（C4）基因的等位基因部分解释。根据先前关于C4和其他补体相关变体与记忆功能之间的关联发现，我们检验了以下假设：基于“补体”系统中已确定的精神分裂症风险等位基因计算的多基因评分将广泛地与记忆功能和相关的脑结构相关。我们使用针对补体基因计算的多基因风险评分（PRS）（不包括C4变体）测试了这一点。对于整个样本，观察到较高的基于补体的PRS得分与较低的记忆得分相关（N= 620，F变化= 8.25；p = .004）。还观察到较高的PRS与较低的海马体积之间存在显着相关性（N = 216，R ²变化= 0.016，p= .015）。但是，在校正了与更一般的皮质厚度，表面积或总脑体积指数的关联的进一步测试后，这些指数均与补体无关，与海马体积的关联变得不显着。对海马亚区的事后分析表明补体PRS与几个海马亚区之间存在关联，这一发现似乎特别受患者样本驱动。总之，我们的研究为基于补体的精神分裂症PRS与记忆功能和海马体积变化之间的关联提供了提示性证据。