title: Host genetic variation in mucosal immunity pathways influences the upper airway microbiome.
abstract: The degree to which host genetic variation can modulate microbial communities in humans remains an open question. Here, we performed a genetic mapping study of the microbiome in two accessible upper airway sites, the nasopharynx and the nasal vestibule, during two seasons in 144 adult members of a founder population of European decent.
  
  
  
  We estimated the relative abundances (RAs) of genus level bacteria from 16S rRNA gene sequences and examined associations with 148,653 genetic variants (linkage disequilibrium [LD] r2< 0.5) selected from among all common variants discovered in genome sequences in this population. We identified 37 microbiome quantitative trait loci (mbQTLs) that showed evidence of association with the RAs of 22 genera (q < 0.05) and were enriched for genes in mucosal immunity pathways. The most significant association was between the RA of Dermacoccus (phylum Actinobacteria) and a variant 8 kb upstream of TINCR (rs117042385; p = 1.61 × 10-8; q = 0.002), a long non-coding RNA that binds to peptidoglycan recognition protein 3 (PGLYRP3) mRNA, a gene encoding a known antimicrobial protein. A second association was between a missense variant in PGLYRP4 (rs3006458) and the RA of an unclassified genus of family Micrococcaceae (phylum Actinobacteria) (p = 5.10 × 10-7; q = 0.032).
  
  
  
  Our findings provide evidence of host genetic influences on upper airway microbial composition in humans and implicate mucosal immunity genes in this relationship.
authors.affiliation: Department of Human Genetics, University of Chicago, Chicago, IL, 60637, USA. cigartua@uchicago.edu.
authors.forename: Catherine
authors.initials: C
authors.lastname: Igartua
authors.affiliation: Department of Human Genetics, University of Chicago, Chicago, IL, 60637, USA.|Department of Molecular Biology and Genetics, Cornell University, Ithaca, NY, 14853, USA.
authors.forename: Emily R
authors.initials: ER
authors.lastname: Davenport
authors.affiliation: Department of Human Genetics, University of Chicago, Chicago, IL, 60637, USA.|Department of Medicine, University of Chicago, Chicago, IL, 60637, USA.
authors.forename: Yoav
authors.initials: Y
authors.lastname: Gilad
authors.affiliation: Department of Human Genetics, University of Chicago, Chicago, IL, 60637, USA.|Department of Medicine, University of Chicago, Chicago, IL, 60637, USA.|Department of Statistics, University of Chicago, Chicago, IL, 60637, USA.
authors.forename: Dan L
authors.initials: DL
authors.lastname: Nicolae
authors.affiliation: Section of Otolaryngology-Head and Neck Surgery, Department of Surgery, University of Chicago, Chicago, IL, 60637, USA.
authors.forename: Jayant
authors.initials: J
authors.lastname: Pinto
authors.affiliation: Department of Human Genetics, University of Chicago, Chicago, IL, 60637, USA. c-ober@bsd.uchicago.edu.
authors.forename: Carole
authors.initials: C
authors.lastname: Ober
mesh_terms: D039903:Actinobacteria / Q000145:classification* / Q000235:genetics* / Q000302:isolation & purification; D000293:Adolescent; D000328:Adult; D000368:Aged; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism; D002874:Chromosome Mapping; D005260:Female; D014644:Genetic Variation / Q000235:genetics; D006801:Humans; D018928:Immunity, Mucosal / Q000235:genetics* / Q000276:immunology; D008297:Male; D064307:Microbiota / Q000235:genetics* / Q000276:immunology; D008875:Middle Aged; D009305:Nasopharynx / Q000382:microbiology*; D009666:Nose / Q000382:microbiology*; D040641:Quantitative Trait Loci / Q000235:genetics; D012336:RNA, Ribosomal, 16S / Q000235:genetics; D055815:Young Adult
chemical_list: D002352:Carrier Proteins; D012336:RNA, Ribosomal, 16S; C118897:peptidoglycan recognition protein
keywords: GWAS; Gene-environment; Host-microbe interactions; Microbiome; Nasal; QTL mapping; Upper airways