Treccani Mirko, Maggioni Lucia, Di Giovanni Claudia, Veschetti Laura, Cristofalo Doriana, Patuzzo Cristina, Lasalvia Antonio, Ristic Branko, Kumar Roushan, Ruggeri Mirella, Bonetto Chiara, Malerba Giovanni, Tosato Sarah
GM Lab, Department of Surgical Sciences, Dentistry, Gynaecology and Paediatrics, University of Verona, 37134 Verona, Italy.
Department of Neuroscience, Biomedicine and Movement Sciences, Section of Psychiatry, University of Verona, 37134 Verona, Italy.
Genes (Basel). 2025 Apr 7;16(4):439. doi: 10.3390/genes16040439.
Psychosis, particularly schizophrenia (SZ), is influenced by genetic and environmental factors. The neurodevelopmental hypothesis suggests that genetic factors affect neuronal circuit connectivity during perinatal periods, hence causing the onset of the diseases. In this study, we performed a genome-wide association study (GWAS) in a sample of the first episode of psychosis (FEP).
A sample of 147 individuals diagnosed with non-affective psychosis and 102 controls were recruited and assessed. After venous blood and DNA extraction, the samples were genotyped. Genetic data underwent quality controls, genotype imputation, and a case-control genome-wide association study (GWAS). After the GWAS, results were investigated using an in silico functional mapping and annotation approach.
Our GWAS showed the association of 27 variants across 13 chromosomes at genome-wide significance ( < 1 × 10) and a total of 1976 candidate variants across 188 genes at suggestive significance ( < 1 × 10), mostly mapping in non-coding or intergenic regions. Gene-based tests reported the association of the SUFU ( = 4.8 × 10) and NCAN ( = 1.6 × 10) genes. Gene-sets enrichment analyses showed associations in the early stages of life, spanning from 12 to 24 post-conception weeks ( < 1.4 × 10) and in the late prenatal period ( = 1.4 × 10), in favor of the neurodevelopmental hypothesis. Moreover, several matches with the GWAS Catalog reported associations with strictly related traits, such as SZ, as well as with autism spectrum disorder, which shares some genetic overlap, and risk factors, such as neuroticism and alcohol dependence.
The resulting genetic associations and the consequent functional analysis displayed common genetic liability between the non-affective psychosis, related traits, and risk factors. In sum, our investigation provided novel hints supporting the neurodevelopmental hypothesis in SZ and-in general-in non-affective psychoses.
精神病，尤其是精神分裂症（SZ），受遗传和环境因素影响。神经发育假说认为，遗传因素在围产期影响神经元回路的连通性，从而导致疾病的发作。在本研究中，我们对首发精神病（FEP）样本进行了全基因组关联研究（GWAS）。
招募并评估了147名被诊断为非情感性精神病的个体和102名对照。采集静脉血并提取DNA后，对样本进行基因分型。对遗传数据进行质量控制、基因型填充和病例对照全基因组关联研究（GWAS）。GWAS之后，使用计算机功能图谱和注释方法对结果进行研究。
我们的GWAS显示，13条染色体上的27个变异在全基因组水平具有显著相关性（<1×10），188个基因中的1976个候选变异在提示性水平具有显著相关性（<1×10），大多数位于非编码或基因间区域。基于基因的测试报告了SUFU基因（=4.8×10）和NCAN基因（=1.6×10）的相关性。基因集富集分析显示，在生命早期（受孕后12至24周，<1.4×10）和产前后期（=1.4×10）存在相关性，支持神经发育假说。此外，与GWAS目录的一些匹配报告了与严格相关性状（如SZ）以及与具有一些遗传重叠的自闭症谱系障碍和风险因素（如神经质和酒精依赖）的相关性。
所得到的遗传关联以及随之而来的功能分析显示了非情感性精神病、相关性状和风险因素之间存在共同的遗传易感性。总之，我们的研究提供了新的线索，支持SZ以及一般非情感性精神病中的神经发育假说。
