This study explores the degree to which genetic influences on psychotic experiences are stable across adolescence and adulthood, and their overlap with psychiatric disorders. Genome-wide association results were obtained for adolescent psychotic experiences and negative symptom traits (N = 6297–10,098), schizotypy (N = 3967–4057) and positive psychotic experiences in adulthood (N = 116,787–117,794), schizophrenia (N = 150,064), bipolar disorder (N = 41,653), and depression (N = 173,005). Linkage disequilibrium score regression was used to estimate genetic correlations. Implicated genes from functional and gene-based analyses were compared. Mendelian randomization was performed on trait pairs with significant genetic correlations. Results indicated that subclinical auditory and visual hallucinations and delusions of persecution during adulthood were significantly genetically correlated with schizophrenia (r_g = 0.27–0.67) and major depression (r_g = 0.41–96) after correction for multiple testing. Auditory and visual subclinical hallucinations were highly genetically correlated (r_g = 0.95). Cross-age genetic correlations for psychotic experiences were not significant. Gene mapping and association analyses revealed 14 possible genes associated with psychotic experiences that overlapped across age for psychotic experiences or between psychotic experiences and psychiatric disorders. Mendelian randomization indicated bidirectional associations between auditory and visual hallucinations in adults but did not support causal relationships between psychotic experiences and psychiatric disorders. These findings indicate that psychotic experiences in adulthood may be more linked genetically to schizophrenia and major depression than psychotic experiences in adolescence. Our study implicated specific genes that are associated with psychotic experiences across development, as well as genes shared between psychotic experiences and psychiatric disorders.

这项研究探讨了遗传对精神病经历的影响在青春期和成年期的稳定程度，以及它们与精神疾病的重叠。获得了青少年精神病经历和阴性症状特征（ N = 6297–10,098）、精神分裂症（ N = 3967–4057）和成年期积极精神病经历（ N = 116,787–117,794）、精神分裂症（ N = 150,064）的全基因组关联结果）、躁郁症（ N = 41,653）和抑郁症（ N = 173,005）。使用连锁不平衡评分回归来估计遗传相关性。比较了功能分析和基于基因的分析中涉及的基因。对具有显着遗传相关性的性状对进行孟德尔随机化。结果表明，经过多重测试校正后，成年期亚临床幻听、幻视和受迫害妄想与精神分裂症（ r _g = 0.27-0.67）和重性抑郁症（ r _g = 0.41-96）具有显着的遗传相关性。听觉和视觉亚临床幻觉具有高度遗传相关性（ r _g = 0.95）。精神病经历的跨年龄遗传相关性并不显着。基因图谱和关联分析揭示了 14 个可能与精神病经历相关的基因，这些基因在不同年龄段的精神病经历或精神病经历与精神疾病之间重叠。孟德尔随机化表明成人幻听和幻视之间存在双向关联，但不支持精神病经历与精神疾病之间的因果关系。 这些发现表明，与青春期的精神病经历相比，成年期的精神病经历可能与精神分裂症和重度抑郁症有更多的遗传相关性。我们的研究涉及与整个发育过程中的精神病经历相关的特定基因，以及精神病经历和精神疾病之间共享的基因。