Postgraduate Program in Epidemiology, Universidade Federal de Pelotas, Pelotas, Brazil.
Postgraduate Program in Genetics and Molecular Biology, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil.
Prog Neuropsychopharmacol Biol Psychiatry. 2021 Mar 2;106:110153. doi: 10.1016/j.pnpbp.2020.110153. Epub 2020 Oct 30.
The gut microbiome is associated with psychiatric disorders; however, the molecular mechanisms mediating this association are poorly understood. The ability of host genetics to modulate the gut microbiome may be an important factor in understanding the association. In this study, we aimed to evaluate the role of genetic variants associated with the gut microbiome in the susceptibility of individuals to four psychiatric disorders: schizophrenia (SCZ), attention-deficit/hyperactivity disorder (ADHD), autism spectrum disorder (ASD), and major depressive disorder (MDD). A total of 201 host genetic markers associated with microbiome outcomes and reported in available genome-wide association studies (GWAS) were included in the analyses. We searched for these variants in the summary statistics of the largest GWAS on these disorders to date, which were published by the Psychiatric Genomic Consortium, and performed gene-based and gene set association analyses. Two variants were significantly associated with ASD (rs9401458 and rs9401452) and one with MDD (rs75036654). For the gene-based association analysis, eight genes were associated with SCZ (ASIC2, KCND3, ITSN1, SIPA1L3, RBMS3, BANK1, CSMD1, and LHFPL3), one with MDD (ACTL8), two with ADHD (C14orf39 and FBXL17), and one with ASD (PINX). The gene set comprising 83 genes was associated with SCZ (p = 0.047). These findings suggest that genes related to microbiome composition may affect the susceptibility of individuals to psychiatric disorders, mainly schizophrenia. Although less robust, the associations with ASD, ADHD, and MDD cannot be discarded.
肠道微生物群与精神疾病有关；然而，介导这种关联的分子机制尚不清楚。宿主遗传学调节肠道微生物群的能力可能是理解这种关联的一个重要因素。在这项研究中，我们旨在评估与肠道微生物群相关的遗传变异在个体易患四种精神疾病（精神分裂症、注意缺陷/多动障碍、自闭症谱系障碍和重度抑郁症）中的作用。共有 201 个与微生物组结果相关的宿主遗传标记，并在现有的全基因组关联研究（GWAS）中报告，这些标记被纳入分析。我们在迄今为止由精神疾病基因组学联盟发表的这些疾病的最大 GWAS 的汇总统计数据中寻找这些变体，并进行了基于基因和基因集的关联分析。两个变体与 ASD 显著相关（rs9401458 和 rs9401452），一个与 MDD 相关（rs75036654）。对于基于基因的关联分析，有 8 个基因与 SCZ 相关（ASIC2、KCND3、ITSN1、SIPA1L3、RBMS3、BANK1、CSMD1 和 LHFPL3），1 个与 MDD 相关（ACTL8），2 个与 ADHD 相关（C14orf39 和 FBXL17），1 个与 ASD 相关（PINX）。包含 83 个基因的基因集与 SCZ 相关（p=0.047）。这些发现表明，与微生物组组成相关的基因可能影响个体易患精神疾病的易感性，主要是精神分裂症。尽管不太稳健，但不能排除与 ASD、ADHD 和 MDD 的关联。
