Human Genetics

, Volume 136, Issue 4, pp 387–397

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
Original Investigation

DOI: 10.1007/s00439-017-1764-0

Cite this article as:
Nakagome, S., Chinen, H., Iraha, A. et al. Hum Genet (2017) 136: 387. doi:10.1007/s00439-017-1764-0

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.

Supplementary material

439_2017_1764_MOESM1_ESM.docx (286 kb)
Supplementary material 1 (DOCX 285 kb)

Copyright information

© Springer-Verlag Berlin Heidelberg 2017

Authors and Affiliations

  • Shigeki Nakagome
    • 1
    • 2
    • 3
    • 16
  • Hiroshi Chinen
    • 4
  • Atsushi Iraha
    • 4
  • Akira Hokama
    • 4
  • Yasuaki Takeyama
    • 5
  • Shotaro Sakisaka
    • 5
  • Toshiyuki Matsui
    • 6
  • Judith R. Kidd
    • 7
  • Kenneth K. Kidd
    • 7
  • Heba S. Said
    • 8
    • 9
    • 10
  • Wataru Suda
    • 8
  • Hidetoshi Morita
    • 11
    • 12
  • Masahira Hattori
    • 8
    • 9
  • Tsunehiko Hanihara
    • 1
  • Ryosuke Kimura
    • 13
  • Hajime Ishida
    • 13
  • Jiro Fujita
    • 14
  • Fukunori Kinjo
    • 4
  • Shuhei Mano
    • 2
    • 12
    • 15
  • Hiroki Oota
    • 1
  1. 1.Department of AnatomyKitasato University School of MedicineSagamiharaJapan
  2. 2.Risk Analysis Research CenterThe Institute of Statistical MathematicsTachikawaJapan
  3. 3.School of Medicine, Faculty of Health SciencesTrinity College Dublin, the University of DublinDublin 2Ireland
  4. 4.Department of EndoscopyUniversity of the Ryukyus HospitalOkinawaJapan
  5. 5.Department of Gastroenterology and MedicineFukuoka University Faculty of MedicineFukuokaJapan
  6. 6.Department of GastroenterologyFukuoka University Chikushi HospitalFukuokaJapan
  7. 7.Department of GeneticsYale University School of MedicineNew HavenUSA
  8. 8.Department of Computational BiologyGraduate School of Frontier Sciences, University of TokyoChibaJapan
  9. 9.Graduate School of Advanced Science and EngineeringWaseda UniversityTokyoJapan
  10. 10.Department of Microbiology and ImmunologyFaculty of Pharmacy, Mansoura UniversityMansouraEgypt
  11. 11.Graduate School of Environmental and Life ScienceOkayama UniversityOkayamaJapan
  12. 12.CREST, Japan Science and Technology AgencyKawaguchiJapan
  13. 13.Department of Human Biology and AnatomyGraduate School of Medicine, University of the RyukyusOkinawaJapan
  14. 14.Department of Infectious, Respiratory, and Digestive Medicine, Control and Prevention of Infectious Diseases, Graduate School of MedicineUniversity of the RyukyusOkinawaJapan
  15. 15.Department of Mathematical Analysis and Statistical InferenceThe Institute of Statistical MathematicsTokyoJapan
  16. 16.Trinity Centre for Health Sciences Room 0.79St. James’s HospitalDublin 8Ireland

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