Despite the meteoric rise in genome-wide association studies for metabolic diseases (MetD) over the last few years, our understanding of the pathogenesis of these diseases is still far from complete. Recent developments have established that MetD arises from complex interactions between host genetics, the gut microbiome and the environment. However, our knowledge of the genetic and microbiome components involved and the underlying molecular mechanisms remains limited. Here, we review and summarize recent studies investigating the genetic and microbiome basis of MetD. Then, given the critical importance of study-individual’s ancestry in these studies, we leverage 4932 whole-genome sequence samples from 18 worldwide ethnic groups to examine genetic diversity in currently reported variants associated with MetD. The analyses show marked differences in gene-specific proportion of pathogenic single-nucleotide polymorphisms (SNPs) and gene-specific SNPs MAFs across ethnic groups, highlighting the importance of population- and ethnic-specific investigations in pinpointing the causative factors for MetD. We conclude with a discussion of research areas where further investigation on interactions between host genetics, microbiome and the environment is needed.

中文翻译：

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剖析微生物组相关代谢疾病的全基因组研究。

尽管在过去几年中代谢疾病 (MetD) 的全基因组关联研究迅速增加，但我们对这些疾病发病机制的了解仍远未完成。最近的发展表明，MetD 源于宿主遗传学、肠道微生物组和环境之间复杂的相互作用。然而，我们对所涉及的遗传和微生物组成分以及潜在分子机制的了解仍然有限。在这里，我们回顾和总结了最近调查 MetD 的遗传和微生物组基础的研究。然后，鉴于研究个体的祖先在这些研究中至关重要，我们利用来自全球 18 个种族的 4932 个全基因组序列样本来检查当前报告的与 MetD 相关的变异的遗传多样性。分析显示，跨种族的致病性单核苷酸多态性 (SNP) 和基因特异性 SNP MAF 的基因特异性比例存在显着差异，突出了人群和种族特异性调查在查明 MetD 致病因素方面的重要性。我们最后讨论了需要进一步研究宿主遗传学、微生物组和环境之间相互作用的研究领域。