This systematic review and meta-analysis synthesizes current evidence on associations between genetic polymorphisms of human leukocyte antigen (HLA) class I and II molecules, which play key roles in antigen presentation and immune response regulation, and brain imaging phenotypes across various neurological and psychiatric conditions. The strongest associations were observed in multiple sclerosis (MS), where HLA-DRB1*15:01 was linked to increased lesion volume and disease progression. Meta-analyses revealed significant pooled effect sizes for both T1 and T2 lesion volumes. Emerging evidence also suggests that variants in HLA class I and II genes contribute to brain structural changes associated with age-related cognitive decline, schizophrenia and Gulf War illness. Our findings revealed greater patterns of association between HLA class II polymorphisms with brain imaging implications as compared to class I in neurodegenerative conditions. Considering HLA class II roles in exogenous protein/peptide presentation, this highlights the potential importance of neuroimmune-environmental interactions as contributing factors to disease pathogenesis and progression. Population-based studies from the UK Biobank highlight the potential influence of HLA class I and II genetic polymorphisms on brain structure beyond disease-specific contexts, suggesting broader implications for neurodevelopment and neurodegeneration. Despite these emerging insights, the limited availability of studies using imaging modalities beyond structural MRI, along with inconsistent findings within specific diseases and across conditions, underscores the need for further investigation into the mechanistic contributions of specific genetic variants on impacting brain structural and functional outcomes. Future research should include larger, more diverse study cohorts and employ advanced genotyping technologies to provide a more comprehensive investigations of HLA's role on brain health across the lifespan.

Keywords: Human leukocyte antigen (HLA); brain imaging; genetic polymorphisms; magnetic resonance imaging (MRI); multiple sclerosis (MS).

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这项系统综述和荟萃分析综合了当前关于人类白细胞抗原（HLA）I类和II类分子基因多态性与各种神经学和精神疾病中脑成像表型之间关联的证据。在多发性硬化症（MS）中观察到了最强的关联，其中HLA-DRB1*15:01与病灶体积增大及病情进展相关联。荟萃分析揭示了T1和T2病灶体积的显著合并效应大小。新兴证据还表明，HLA I类和II类基因变异对与年龄相关的认知下降、精神分裂症和海湾战争综合征相关的脑结构变化有贡献。我们的研究发现，在神经退行性疾病中，HLA II类多态性与具有脑成像意义的相关模式相比HLA I类更为显著。鉴于HLA II类在异源蛋白质/肽的呈现中的作用，这突显了神经免疫-环境相互作用作为疾病发病机制和发展因素的重要性。来自英国生物银行的人口研究强调了HLA I类和II类基因多态性对脑结构潜在影响超越特定疾病的背景，暗示其在神经发育和神经退行性疾病中具有更广泛的意义。尽管有这些新兴的见解，但使用除结构性磁共振成像（MRI）以外的影像学方法的研究有限，以及在同一疾病内部和跨不同条件中的发现不一致，强调了进一步研究特定基因变异对脑结构和功能结果影响机制贡献的需求。未来的研究应包括更大、更多样化的研究队列，并采用先进的基因分型技术，以提供更全面地调查HLA在整个生命周期中对脑健康的作用。

关键词：人类白细胞抗原（HLA）；脑成像；遗传多态性；磁共振成像（MRI）；多发性硬化症（MS）。

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