Host genetics and microbiome associations through the lens of genome wide association studies

• Published in: Current opinion in microbiology Vol. 44; pp. 9 - 19
• Main Authors: Weissbrod, Omer, Rothschild, Daphna, Barkan, Elad, Segal, Eran
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 01.08.2018
• ISSN: 1369-5274; 1879-0364
• DOI: 10.1016/j.mib.2018.05.003

•Host genetics explains a small fraction of variability in gut microbiome composition.•Existing studies are underpowered to identify microbiome-associated genetic variants.•Lessons learned from GWAS can be applied to microbiome studies.•Global analyses that consider all taxa jointly can increase detection power. Recent studies indicate that the gut microbiome is partially heritable, motivating the need to investigate microbiome–host genome associations via microbial genome-wide association studies (mGWAS). Existing mGWAS demonstrate that microbiome–host genotype associations are typically weak and are spread across multiple variants, similar to associations often observed in genome-wide association studies (GWAS) of complex traits. Here we reconsider mGWAS by viewing them through the lens of GWAS, and demonstrate that there are striking similarities between the challenges and pitfalls faced by the two study designs. We further advocate the mGWAS community to adopt three key lessons learned over the history of GWAS: firstly, adopting uniform data and reporting formats to facilitate replication and meta-analysis efforts; secondly, enforcing stringent statistical criteria to reduce the number of false positive findings; and thirdly, considering the microbiome and the host genome as distinct entities, rather than studying different taxa and single nucleotide polymorphism (SNPs) separately. Finally, we anticipate that mGWAS sample sizes will have to increase by orders of magnitude to reproducibly associate the host genome with the gut microbiome.