Confounding effects of microbiome on the susceptibility of TNFSF15 to Crohn’s disease in the Ryukyu Islands

Shigeki Nakagome, Hiroshi Chinen, Atsushi Iraha, Akira Hokama, Yasuaki Takeyama, Shotaro Sakisaka, Toshiyuki Matsui, Judith R. Kidd, Kenneth K. Kidd, Heba S. Said, Wataru Suda, Hidetoshi Morita, Masahira Hattori, Tsunehiko Hanihara, Ryosuke Kimura, Hajime Ishida, Jiro Fujita, Fukunori Kinjo, Shuhei Mano, Hiroki Oota

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    6 Citations (Scopus)

    Abstract

    Crohn’s disease (CD) involves chronic inflammation in the gastrointestinal tract due to dysregulation of the host immune response to the gut microbiome. Even though the host-microbiome interactions are likely contributors to the development of CD, a few studies have detected genetic variants that change bacterial compositions and increase CD risk. We focus on one of the well-replicated susceptible genes, tumor necrosis factor superfamily member 15 (TNFSF15), and apply statistical analyses for personal profiles of genotypes and salivary microbiota collected from CD cases and controls in the Ryukyu Islands, southernmost islands of the Japanese archipelago. Our association test confirmed the susceptibility of TNFSF15 in the Ryukyu Islands. We found that the recessive model was supported to fit the observed genotype frequency of risk alleles slightly better than the additive model, defining the genetic effect on CD if a pair of the chromosomes in an individual consists of all risk alleles. The combined analysis of haplotypes and salivary microbiome from a small set of samples showed a significant association of the genetic effect with the increase of Prevotella, which led to a significant increase of CD risk. However, the genetic effect on CD disappeared if the abundance of Prevotella was low, suggesting the genetic contribution to CD is conditionally independent given a fixed amount of Prevotella. Although our statistical power is limited due to the small sample size, these results support an idea that the genetic susceptibility of TNFSF15 to CD may be confounded, in part, by the increase of Prevotella.

    Original languageEnglish
    Pages (from-to)387-397
    Number of pages11
    JournalHuman Genetics
    Volume136
    Issue number4
    DOIs
    Publication statusPublished - 2017 Apr 1

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    ASJC Scopus subject areas

    • Genetics
    • Genetics(clinical)

    Cite this

    Nakagome, S., Chinen, H., Iraha, A., Hokama, A., Takeyama, Y., Sakisaka, S., Matsui, T., Kidd, J. R., Kidd, K. K., Said, H. S., Suda, W., Morita, H., Hattori, M., Hanihara, T., Kimura, R., Ishida, H., Fujita, J., Kinjo, F., Mano, S., & Oota, H. (2017). Confounding effects of microbiome on the susceptibility of TNFSF15 to Crohn’s disease in the Ryukyu Islands. Human Genetics, 136(4), 387-397. https://doi.org/10.1007/s00439-017-1764-0