School of Public Health, Health Science Center, Xi'an Jiaotong University, Xi'an, China.
Brief Bioinform. 2020 May 21;21(3):1016-1022. doi: 10.1093/bib/bbz034.
Psychiatric disorders are a group of complex psychological syndromes with high prevalence. It has been reported that gut microbiota has a dominant influence on the risks of psychiatric disorders through gut microbiota-brain axis. We extended the classic gene set enrichment analysis (GSEA) approach to detect the association between gut microbiota and complex diseases using published genome-wide association study (GWAS) and GWAS of gut microbiota summary data. We applied our approach to real GWAS data sets of five psychiatric disorders, including attention deficiency/hyperactive disorder (ADHD), autism spectrum disorder (AUT), bipolar disorder (BD), schizophrenia (SCZ) and major depressive disorder (MDD). To evaluate the performance of our approach, we also tested the genetic correlations of obesity and type 2 diabetes with gut microbiota. We identified several significant associations between psychiatric disorders and gut microbiota, such as ADHD and genus Desulfovibrio (P = 0.031), order Clostridiales (P = 0.034). For AUT, association signals were observed for genera Bacteroides (P = 0.012) and Desulfovibrio (P = 0.033). Genus Desulfovibrio (P = 0.005) appeared to be associated with BD. For MDD, association signals were observed for genus Desulfovibrio (P = 0.003), order Clostridiales (P = 0.004), family Lachnospiraceae (P = 0.007) and genus Bacteroides (P = 0.007). Genus Desulfovibrio (P = 0.012) and genus Bacteroides (P = 0.038) appeared to be associated with SCZ. Our study results provide novel clues for revealing the roles of gut microbiota in psychiatric disorders. This study also illustrated the good performance of GSEA approach for exploring the relationships between gut microbiota and complex diseases.
精神障碍是一组具有高患病率的复杂心理综合征。据报道，通过肠脑轴，肠道微生物群对精神障碍的风险有主导影响。我们扩展了经典的基因集富集分析（GSEA）方法，利用已发表的全基因组关联研究（GWAS）和肠道微生物组汇总数据的 GWAS 来检测肠道微生物组与复杂疾病之间的关联。我们将我们的方法应用于五种精神障碍的真实 GWAS 数据集，包括注意缺陷/多动障碍（ADHD）、自闭症谱系障碍（AUT）、双相情感障碍（BD）、精神分裂症（SCZ）和重度抑郁症（MDD）。为了评估我们方法的性能，我们还测试了肥胖症和 2 型糖尿病与肠道微生物组的遗传相关性。我们确定了精神障碍与肠道微生物组之间的一些显著关联，例如 ADHD 与脱硫弧菌属（P = 0.031）、梭菌目（P = 0.034）。对于 AUT，观察到细菌属（P = 0.012）和脱硫弧菌属（P = 0.033）的关联信号。脱硫弧菌属（P = 0.005）似乎与 BD 有关。对于 MDD，观察到脱硫弧菌属（P = 0.003）、梭菌目（P = 0.004）、lachnospiraceae 科（P = 0.007）和细菌属（P = 0.007）的关联信号。脱硫弧菌属（P = 0.012）和细菌属（P = 0.038）似乎与 SCZ 有关。我们的研究结果为揭示肠道微生物群在精神障碍中的作用提供了新的线索。这项研究还说明了 GSEA 方法在探索肠道微生物组与复杂疾病之间关系方面的良好性能。
