Skip to main content
. Author manuscript; available in PMC: 2018 May 27.
Published in final edited form as: Annu Rev Genet. 2017 Sep 20;51:413–433. doi: 10.1146/annurev-genet-110711-155532

Table 1.

Summary of human microbiome genome-wide association studies

Reference Body site Sample size Subject cohort Subject population Data type Microbiome attributes examined Number of
variants		 Significance threshold
Blekhman et al. 15 sites within the oral and nasal cavities, gastrointestinal tract, and on skin1 93 Human Microbiome Project United States 16S Beta-diversity (first 5 PCs), 615 taxa (genus to phylum) 33,814 Beta-diversity pathway-based analysis: P ≤ 10−6
Taxa: Genome- wide
Q-value < 0.1
Main findings:
Beta-diversity: enrichment of genes involved in leptin signaling in obesity, several other immunity- related pathways, and KEGG pathway primary bile acid biosynthesis.
Taxa: 83 associations including HLA-DRA (Selenomonas in the throat), TLR1 (Lautropia in the tongue dorsum), LCT (Bifidobacterium in the GI tract).
Davenport et al. Stool 127 North American Hutterites 16S Alpha-diversity, 102 taxa (genus to phylum) 2 212,153 2 Genome-wide
Q-value < 0.2
Main findings:
Significant associations with at least 8 bacterial taxa including Akkermansia with a variant near PLD1.
Gene-set enrichment analysis identified enrichment of variants involved in olfactory receptor activity with 5 taxa.
Stomach and intestines were identified as candidate tissues where host genetic variation may be acting to influence bacterial abundance of genus Faecalibacterium.
Hua et al. Lung 147 Environment And Genetics in Lung cancer Etiology Italy 16S Beta diversity, alpha diversity, bacterial taxa (number not specified) 383,263 P < 5 × 10−8
Main findings:
No significant associations after correcting for skewness and kurtosis of beta-diversity distributions.
Goodrich et al. Stool 2,139 TwinsUK United Kingdom 16S Beta diversity, alpha diversity, 782 OTUs, 163 taxa (genus to phylum) 1,300,091 Genome-wide BH adjusted P- value < 0.1
Main findings:
92 significant associations with OTUs and taxa. Includes an association between the heritable taxon Unclassified Clostridiaceae with SLIT3 and Bifidobacterium with LCT.
Beta diversity was associated with UHRF2.
Association between Akkermansia and predicted tissue-specific expression of SIGLEC15
Bonder et al. Stool 1,514
Discovery: 984
Replication: 530		 Discovery: LifeLines- Deep
Replication: 500FG and MIBS-CO		 Netherlands Meta- genomics 219 microbial taxa,
636 MetaCyc pathways, 661 Gene Ontology (GO)		 8.1 million Discovery:
P < 5 × 10−5
Replication: P < 0.01 same direction
Meta-analysis: P < 5 × 10−8
Main findings:
Meta-analysis results: 9 loci associated to bacteria, 21 loci associated to MetaCyc and 12 loci associated to GO terms
Strongest association with taxa: Blautia with SNPs near LINGO2 and Methanobacteriaceae with an extended long noncoding RNA (lncRNA).
Strongest association with MetaCyc pathways: pathway involved in plant- derived steroid degradation with SORCS2 and SLIT3.
Two GO terms were associated with SNPs near clusters of C-type lectin domain family 4 genes.
GG genotype at SNP rs4988235 (near LCT gene) was associated with high Bifidobacterium.
Turpin et al. Stool 1,561
Discovery: 1,098
Replication: 463		 Genetic Environmental Microbial (GEM) Project Discovery: Canada and United States
Replication: Canada, United States, and Israel		 16S Alpha diversity, 166 taxa (genus to phylum) 3,727,707 Genome-wide P < 5 × 10−8
Study-wise correcting for number of effective tests: P < 4.13 × 10−10
Main findings:
58 genome-wide significant associations with taxa, 6 of which achieved study-wise significance.
4 loci were replicated: Rikenellaceae with SNPs near UBR3, Faecalibacterium with CNTN6, Lachnospira with DMRTB1, and Eubacterium with SALL3.
Wang et al. Stool Discovery: 1,812
Replication: 371		 PopGen and FoCus
Replication: FoCus obesity		 Germany 16S Beta diversity, 40 OTUs, 58 taxa (genus to phylum) 6,344,846 P < 5 × 10−8
Main findings:
42 loci associated with beta diversity including variants in the VDR gene.
21 of the 42 beta-diversity associated loci replicate.
54 significant associations with taxa. Unclassified Porphyromonadaceae was associated with SLC2A9. Several lncRNA including LINC01192 with Lactobacillales.
Igartua et al. Nasopharynx
Nasal vestibule		 144 North American Hutterites 16S nasal vestibule: 76 genera nasopharynx: 90 genera 2 148,653 2 Genome-wide
Q-value < 0.05
Main findings:
37 associations with genera, these genetic loci are enriched for genes in mucosal immunity pathways. Associations included Dermacoccus with a SNP near TINCR and an unclassified genus of family Micrococcaceae with PGLYRP4.
1

HMP specific sites tested: Attached keratinized gingiva (gums), Buccal mucosa (cheek), Hard palate, Palatine tonsils, Saliva, Subgingival plaque, Supragingival plaque, Throat, Tongue dorsum, Anterior nares (nostrils), Left and right antecubital fossa (inner elbow), Left and right retroauricular crease (behind the ear), and Stool.

2

Number reported is from the seasons combined analysis.