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<p>The gut microbiota is associated with human health and disease. Here we conducted a genome-wide association study of host genetic factors influencing gut microbiota composition in 12,652 individuals from the Trøndelag Health Study (HUNT), with replication in Nordic cohorts (<i>n</i> = 16,017–21,976). We identified 12 reproducible SNP–species associations across six genomic loci, including known (<i>LCT</i>, <i>ABO</i>) and novel (<i>HLA-DQB1</i>, <i>MUC12</i>, <i>SLC37A2</i>, <i>FUT2</i>) regions. Additionally, we detected genetic signals associated with gut microbiota functional modules at three loci (<i>LCT</i>, <i>ABO</i>, <i>FUT2</i>). Follow-up analyses suggest that these host–microbiota associations are linked to the pathogenesis of celiac disease and hemorrhoidal disease. Mendelian randomization analyses provided evidence supporting a causal effect of body mass index on gut microbiota composition. These findings highlight the interplay between host genetics and gut microbiota for human health and disease.</p>

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The HUNT study identifies host genetic factors reproducibly associated with human gut microbiota composition

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年2月13日

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  • Marta Riise Moksnes,
  • Eivind Coward,
  • Maria Nethander,
  • Koen Dekkers,
  • Louise Grahnemo,
  • Anna E. Törnqvist,
  • Lei Li,
  • Per Lundmark,
  • Kamalita Pertiwi,
  • Gabriel Baldanzi,
  • Robin Mjelle,
  • Janne Marie Moll,
  • Aron Charles Eklund,
  • Henrik Bjørn Nielsen,
  • Johan Svensson,
  • Arnulf Langhammer,
  • Guro F. Giskeødegård,
  • Ben Brumpton,
  • Rebecka Hjort,
  • Eivind Ness-Jensen,
  • Gunnar Engström,
  • Thaher Pelaseyed,
  • Karl Michaëlsson,
  • Marju Orho-Melander,
  • Tove Fall,
  • Kristian Hveem,
  • Claes Ohlsson

摘要

The gut microbiota is associated with human health and disease. Here we conducted a genome-wide association study of host genetic factors influencing gut microbiota composition in 12,652 individuals from the Trøndelag Health Study (HUNT), with replication in Nordic cohorts (n = 16,017–21,976). We identified 12 reproducible SNP–species associations across six genomic loci, including known (LCT, ABO) and novel (HLA-DQB1, MUC12, SLC37A2, FUT2) regions. Additionally, we detected genetic signals associated with gut microbiota functional modules at three loci (LCT, ABO, FUT2). Follow-up analyses suggest that these host–microbiota associations are linked to the pathogenesis of celiac disease and hemorrhoidal disease. Mendelian randomization analyses provided evidence supporting a causal effect of body mass index on gut microbiota composition. These findings highlight the interplay between host genetics and gut microbiota for human health and disease.