Confounding Effects of Microbiome on the Susceptibility of TNFSF15 to Crohn's Disease in the Ryukyu Islands

• NCJ Number: 252351
• Journal: HUMAN GENETICS Volume: 136 Issue: 4 Dated: April 2017 Pages: 387-397
• Author(s): Shigeki Nakagome; Hiroshi Chinen; Atsushi Iraha; Akira Hukama; 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; Hajume Ishida; Jiro Fujita; Fukunori Kinjo; Shuhei Mano; Hiroki Oota
• Date Published: April 2017
• Length: 11 pages
• Grant Number(s): 2016-DN-BX-0162; 2015-DN-BX-K023
• Agencies: NIJ-Sponsored
• Publication Type: Research (Applied/Empirical); Report (Study/Research); Report (Grant Sponsored); Program/Project Description
• Award: Powerful Forensic Markers Optimized for Massively Parallel Sequencing; Enhancing and Sustaining the ALFRED-FROG-KB Forensic Resource

Annotation

This study focused on one of the well-replicated susceptible genes for Crohn's disease (CD), tumor necrosis factor superfamily member 15 (TNFSF15), and applied 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.

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. The current study's association test confirmed the susceptibility of TNFSF15 in the Ryukyu Islands. Researchers 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 when 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 in CD risk; however, the genetic effect on CD disappeared when the abundance of Prevotella was low, suggesting the genetic contribution to CD is conditionally independent, given a fixed amount of Prevotella. Although the project's statistical power was 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. (Publisher abstract modified)