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

    Research output: Contribution to journalArticle

    5 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

    Fingerprint

    Microbiota
    Islands
    Crohn Disease
    Tumor Necrosis Factor-alpha
    Prevotella
    Genotype
    Genetic Models
    Genetic Predisposition to Disease
    Gene Frequency
    Sample Size
    Haplotypes
    Gastrointestinal Tract
    Chromosomes
    Alleles
    Inflammation

    ASJC Scopus subject areas

    • Genetics
    • Genetics(clinical)

    Cite this

    Nakagome, S., Chinen, H., Iraha, A., Hokama, A., Takeyama, Y., Sakisaka, 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

    Confounding effects of microbiome on the susceptibility of TNFSF15 to Crohn’s disease in the Ryukyu Islands. / Nakagome, Shigeki; Chinen, Hiroshi; Iraha, Atsushi; Hokama, Akira; Takeyama, Yasuaki; Sakisaka, Shotaro; Matsui, Toshiyuki; Kidd, Judith R.; Kidd, Kenneth K.; Said, Heba S.; Suda, Wataru; Morita, Hidetoshi; Hattori, Masahira; Hanihara, Tsunehiko; Kimura, Ryosuke; Ishida, Hajime; Fujita, Jiro; Kinjo, Fukunori; Mano, Shuhei; Oota, Hiroki.

    In: Human Genetics, Vol. 136, No. 4, 01.04.2017, p. 387-397.

    Research output: Contribution to journalArticle

    Nakagome, S, Chinen, H, Iraha, A, Hokama, A, Takeyama, Y, Sakisaka, S, Matsui, T, Kidd, JR, Kidd, KK, Said, HS, 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, vol. 136, no. 4, pp. 387-397. https://doi.org/10.1007/s00439-017-1764-0
    Nakagome, Shigeki ; Chinen, Hiroshi ; Iraha, Atsushi ; Hokama, Akira ; Takeyama, Yasuaki ; Sakisaka, Shotaro ; Matsui, Toshiyuki ; Kidd, Judith R. ; Kidd, Kenneth K. ; Said, Heba S. ; Suda, Wataru ; Morita, Hidetoshi ; Hattori, Masahira ; Hanihara, Tsunehiko ; Kimura, Ryosuke ; Ishida, Hajime ; Fujita, Jiro ; Kinjo, Fukunori ; Mano, Shuhei ; Oota, Hiroki. / Confounding effects of microbiome on the susceptibility of TNFSF15 to Crohn’s disease in the Ryukyu Islands. In: Human Genetics. 2017 ; Vol. 136, No. 4. pp. 387-397.
    @article{1c90b2b351c2404288b12a3dd59d38e8,
    title = "Confounding effects of microbiome on the susceptibility of TNFSF15 to Crohn’s disease in the Ryukyu Islands",
    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.",
    author = "Shigeki Nakagome and Hiroshi Chinen and Atsushi Iraha and Akira Hokama and Yasuaki Takeyama and Shotaro Sakisaka and Toshiyuki Matsui and Kidd, {Judith R.} and Kidd, {Kenneth K.} and Said, {Heba S.} and Wataru Suda and Hidetoshi Morita and Masahira Hattori and Tsunehiko Hanihara and Ryosuke Kimura and Hajime Ishida and Jiro Fujita and Fukunori Kinjo and Shuhei Mano and Hiroki Oota",
    year = "2017",
    month = "4",
    day = "1",
    doi = "10.1007/s00439-017-1764-0",
    language = "English",
    volume = "136",
    pages = "387--397",
    journal = "Human Genetics",
    issn = "0340-6717",
    publisher = "Springer Verlag",
    number = "4",

    }

    TY - JOUR

    T1 - Confounding effects of microbiome on the susceptibility of TNFSF15 to Crohn’s disease in the Ryukyu Islands

    AU - Nakagome, Shigeki

    AU - Chinen, Hiroshi

    AU - Iraha, Atsushi

    AU - Hokama, Akira

    AU - Takeyama, Yasuaki

    AU - Sakisaka, Shotaro

    AU - Matsui, Toshiyuki

    AU - Kidd, Judith R.

    AU - Kidd, Kenneth K.

    AU - Said, Heba S.

    AU - Suda, Wataru

    AU - Morita, Hidetoshi

    AU - Hattori, Masahira

    AU - Hanihara, Tsunehiko

    AU - Kimura, Ryosuke

    AU - Ishida, Hajime

    AU - Fujita, Jiro

    AU - Kinjo, Fukunori

    AU - Mano, Shuhei

    AU - Oota, Hiroki

    PY - 2017/4/1

    Y1 - 2017/4/1

    N2 - 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.

    AB - 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.

    UR - http://www.scopus.com/inward/record.url?scp=85012899390&partnerID=8YFLogxK

    UR - http://www.scopus.com/inward/citedby.url?scp=85012899390&partnerID=8YFLogxK

    U2 - 10.1007/s00439-017-1764-0

    DO - 10.1007/s00439-017-1764-0

    M3 - Article

    C2 - 28197769

    AN - SCOPUS:85012899390

    VL - 136

    SP - 387

    EP - 397

    JO - Human Genetics

    JF - Human Genetics

    SN - 0340-6717

    IS - 4

    ER -