Innovations in sequencing technology have generated voluminous microbial and host genomic data,making it possible to detect these genetic variations and analyze the function influenced by them.Re-cently,many studies have linked such genetic variations to phenotypes through association or compar-ative analysis,which have further advanced our understanding of multiple microbial functions.In this review,we summarized the application of association analysis in microbes like Mycobacterium tubercu-losis,focusing on screening of microbial genetic variants potentially associated with phenotypes such as drug resistance,pathogenesis and novel drug targets etc.;reviewed the application of additional comparative genomic or transcriptomic methods to identify genetic factors associated with functions in microbes;expanded the scope of our study to focus on host genetic factors associated with certain mi-crobes or microbiome and summarized the recent host genetic variations associated with microbial phenotypes,including susceptibility and load after infection of HIV,presence/absence of different taxa,and quantitative traits of microbiome,and lastly,discussed the challenges that may be encountered and the apparent or potential viable solutions.Gene-function analysis of microbe and microbiome is still in its infancy,and in order to unleash its full potential,it is necessary to understand its history,current status,and the challenges hindering its development.