Mas-Bermejo Patricia, Papiol Sergi, Torrecilla Pilar, Lavín Valeria, Kwapil Thomas R, Barrantes-Vidal Neus, Rosa Araceli
Departament de Biologia Evolutiva, Ecologia i Ciències Ambientals, Facultat de Biologia, Universitat de Barcelona, Barcelona, Spain; Institut de Biomedicina de la Universitat de Barcelona (IBUB), Barcelona, Spain.
Institute of Psychiatric Phenomics and Genomics (IPPG), University Hospital, LMU Munich, Munich, Germany; Max Planck Institute of Psychiatry, Munich, Germany; Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), Instituto de Salud Carlos III (ISCIII), Madrid, Spain.
Prog Neuropsychopharmacol Biol Psychiatry. 2025 Jan 10;136:111161. doi: 10.1016/j.pnpbp.2024.111161. Epub 2024 Oct 4.
According to the dimensional view of psychiatric disorders, psychosis is expressed as a continuum in the general population. However, the investigation of the putative genetic aetiological continuity between its clinical and subclinical phenotypes has yielded mixed results. We aimed to replicate previous findings regarding the association of polygenic risk for schizophrenia with subclinical traits (i.e., schizotypy traits and psychotic-like experiences), and to examine the role of sex in this association in a large nonclinical sample.
The Multidimensional Schizotypy Scale and the Community Assessment of Psychic Experiences were assessed in 919 nonclinical participants. Polygenic Risk Scores for schizophrenia (SZ-PRSs) were computed using the PRS-CS method based on the latest genome-wide association study of schizophrenia. Summary statistics derived from the total GWAS sample and stratified by sex were used. Linear regression analyses tested the associations of the SZ-PRSs with the psychometric variables, both in the total sample and by sex.
No associations were found between the SZ-PRSs and the positive, negative or disorganized dimensions of schizotypy in the total sample. Likewise, no associations were found with psychotic-like experiences. However, the sex-stratified analyses revealed a male-specific association with positive schizotypy. Similar results were obtained with the PRSs derived from the sex-stratified summary statistics.
Our results are consistent with the lack of clear evidence of an association between SZ common genetic risk and its subclinical phenotypes. Nevertheless, the male-specific association found suggests that this PRS might explain better the male phenotype, as reported in previous studies. Future studies should put a focus on the role of sex in this association to unravel its sex specificities.
根据精神疾病的维度观点，精神病在普通人群中表现为一个连续体。然而，对其临床和亚临床表型之间假定的遗传病因连续性的研究结果不一。我们旨在重复先前关于精神分裂症多基因风险与亚临床特征（即分裂型特质和类精神病体验）之间关联的研究，并在一个大型非临床样本中研究性别在这种关联中的作用。
对919名非临床参与者进行了多维分裂型量表和精神体验社区评估。使用基于最新精神分裂症全基因组关联研究的PRS-CS方法计算精神分裂症的多基因风险评分（SZ-PRSs）。使用从全基因组关联研究总样本中得出并按性别分层的汇总统计数据。线性回归分析在总样本和按性别分层的样本中测试了SZ-PRSs与心理测量变量之间的关联。
在总样本中，未发现SZ-PRSs与分裂型的阳性、阴性或紊乱维度之间存在关联。同样，也未发现与类精神病体验存在关联。然而，按性别分层的分析显示，男性存在与阳性分裂型的特异性关联。从按性别分层的汇总统计数据得出的多基因风险评分也获得了类似结果。
我们的结果与缺乏关于精神分裂症常见遗传风险与其亚临床表型之间关联的明确证据一致。尽管如此，发现的男性特异性关联表明，如先前研究中所报道的，这种多基因风险评分可能更好地解释男性表型。未来的研究应关注性别在这种关联中的作用，以揭示其性别特异性。
