Clinical and genetic risk factors for decreased bone mineral density in Japanese patients with inflammatory bowel disease

Takeo Naito, Naonobu Yokoyama, Yoichi Kakuta, Kazuko Ueno, Yosuke Kawai, Motoyuki Onodera, Rintaro Moroi, Masatake Kuroha, Yoshitake Kanazawa, Tomoya Kimura, Hisashi Shiga, Katsuya Endo, Masao Nagasaki, Atsushi Masamune, Yoshitaka Kinouchi, Tooru Shimosegawa

Research output: Contribution to journalArticlepeer-review

3 Citations (Scopus)

Abstract

Background and Aim: Patients with inflammatory bowel disease (IBD) are at a high risk of low bone mineral density (BMD). Reportedly, clinical and genetic factors cause low BMD in Caucasians; however, studies in non-Caucasian populations remain scarce. Methods: Clinical risk factors for low BMD were investigated in 266 Japanese patients with IBD, and a genome-wide association analysis (GWAS) was performed using linear regression with associated clinical factors as covariates. Genotyping was performed using a population-optimized genotyping array (Japonica array®). After quality control, the genotype data of 4 384 682 single-nucleotide polymorphisms (SNPs) from 254 patients with IBD were used for GWAS. Results: Body mass index, age, and disease duration were independently associated with the BMD of the femoral neck (P = 1.41E − 13, 1.04E − 5, and 1.58E − 3, respectively), and body mass index and sex were associated with the BMD of the lumbar spine (P = 6.90E − 10 and 6.84E − 3, respectively). In GWAS, 118 and 42 candidate SNPs of the femoral neck and lumbar spine, respectively, were identified. Among 118, 111 candidate SNPs of the femoral neck were located within the SLC22A23 gene, which is a known IBD susceptibility gene (minimum P = 1.42E − 07). Among 42, 18 candidate SNPs of the lumbar spine were located within the MECOM gene, which is associated with osteopenia (minimum P = 5.86E − 07). Interestingly, none of the known loci showed a significant association with BMD. Conclusions: Although clinical risk factors for low BMD in IBD were similar to those in the general population, genetic risk factors were rather different.

Original languageEnglish
Pages (from-to)1873-1881
Number of pages9
JournalJournal of Gastroenterology and Hepatology (Australia)
Volume33
Issue number11
DOIs
Publication statusPublished - 2018 Nov

Keywords

  • genome-wide association analysis
  • inflammatory bowel disease genetics
  • osteoporosis

ASJC Scopus subject areas

  • Hepatology
  • Gastroenterology

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