精神分裂症中罕见破坏性突变的多基因负担

　　A，复合集基因的个体基因级。基因由从左到右的稀有破坏性突变的病例负担进行排名。沿底部的正方形表示每个基因所属的设置。红色和蓝色三角形代表每个基因的病例和控制计数。上面的线代表了该集合最佳测试的统计显着性：即通过排列评估的顶部K基因的重要性。黑线表示真实数据的结果（破坏性MAF< 0.1% composite set analysis). The orange line represents the dummy condition, in which we artificially constructed a set in which the number of genes, statistical enrichment, odds ratio and case/control counts were similar to the real composite set. However, this set included the 25 top-ranked genes from individual gene-based tests (disruptive MAF < 0.1% variants), with the remainder selected at random. The profile of the best test line is markedly different between the real and dummy gene sets (note: truncated at P = 0.0001 reflecting the number of permutations performed). Whereas the dummy P value climbs quickly and then drops to the final aggregate result, the true composite set line continues to climb after 200 genes, indicating that many genes with a single disruptive mutation contribute to the observed set enrichment (rather than a relatively small proportion of the 1,796 genes accounting for the majority of the signal, as in the dummy set). b, Phenotypic characteristics of cases carrying mutations. Relationship between clinical and demographic measures in schizophrenia cases in relation to carrying one or more composite set disruptive risk alleles (MAF < 0.1%). Hospital Discharge Registry (HDR) data (ICD9 codes) were available on 979 of the 990 case carriers. All P values (uncorrected) are two-sided from a case-only joint logistic regression of carrier status (one or more risk alleles) on all admission and demographic variables including year of first and last admissions. The four pairs of columns represent analyses in which we varied the way in which the HDR admission data were represented (for drug abuse, general medication condition, epilepsy and intellectual disability). # admissions, independent variables are the untransformed number of admissions; >X录取，自变量是二进制0/1变量，表示个人是否具有X录入量超过X。在考虑的所有临床/人口统计学指标中，我们观察到，与其他病例相比，综合集合中携带破坏性等位基因的病例的次要诊断发生率提高了，与其他病例相比（基于HDR ICD9代码），携带破坏性等位基因的病例的可能性增加了。

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