Effect of host genetics on the gut microbiome in 7,738 participants of the Dutch Microbiome Project

Nat Genet. 2022 Feb;54(2):143-151. doi: 10.1038/s41588-021-00992-y. Epub 2022 Feb 3.


Host genetics are known to influence the gut microbiome, yet their role remains poorly understood. To robustly characterize these effects, we performed a genome-wide association study of 207 taxa and 205 pathways representing microbial composition and function in 7,738 participants of the Dutch Microbiome Project. Two robust, study-wide significant (P < 1.89 × 10-10) signals near the LCT and ABO genes were found to be associated with multiple microbial taxa and pathways and were replicated in two independent cohorts. The LCT locus associations seemed modulated by lactose intake, whereas those at ABO could be explained by participant secretor status determined by their FUT2 genotype. Twenty-two other loci showed suggestive evidence (P < 5 × 10-8) of association with microbial taxa and pathways. At a more lenient threshold, the number of loci we identified strongly correlated with trait heritability, suggesting that much larger sample sizes are needed to elucidate the remaining effects of host genetics on the gut microbiome.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • ABO Blood-Group System / genetics*
  • Bacterial Physiological Phenomena*
  • Bifidobacterium / physiology
  • Diet
  • Fucosyltransferases / genetics
  • Gastrointestinal Microbiome*
  • Gastrointestinal Tract / microbiology*
  • Genetic Variation*
  • Genome, Human
  • Genome-Wide Association Study
  • Host Microbial Interactions*
  • Humans
  • Lactase / genetics*
  • Metabolic Networks and Pathways
  • Metagenome
  • Multifactorial Inheritance
  • Netherlands
  • Polymorphism, Single Nucleotide
  • Quantitative Trait Loci
  • Sodium Chloride, Dietary
  • Triglycerides / blood


  • ABO Blood-Group System
  • Sodium Chloride, Dietary
  • Triglycerides
  • Fucosyltransferases
  • galactoside 2-alpha-L-fucosyltransferase
  • Lactase