Risk Variants in or Near ZBTB40 AND NFATC1 Increase the Risk of Both IBD and Adverse Bone Health Outcomes Highlighting Common Genetic Underpinnings Across Both Diseases.
Inflamm Bowel Dis
; 29(6): 938-945, 2023 06 01.
Article
in En
| MEDLINE
| ID: mdl-36680554
ABSTRACT
BACKGROUND:
Inflammatory bowel disease (IBD) is associated with an increased risk of osteoporosis and bone fracture. The aims of this study were to (1) confirm the association between IBD and low bone density and (2) test for shared risk variants across diseases.METHODS:
The study cohort included patients from the Michigan Genomics Initiative. Student's t tests (continuous) and chi-square tests (categorical) were used for univariate analyses. Multivariable logistic regression was performed to test the effect of IBD on osteoporosis or osteopenia. Publicly available genome-wide association summary statistics were used to identify variants that alter the risk of IBD and bone density, and Mendelian randomization (MR) was used to identify causal effects of genetically predicted IBD on bone density.RESULTS:
There were 51â 405 individuals in the Michigan Genomics Initiative cohort including 10â 378 (20.2%) cases of osteoporosis or osteopenia and 1404 (2.7%) cases of IBD. Patients with osteoporosis or osteopenia were more likely to be older (64 years of age vs 56 years of age; P < .001), female (67% vs 49%; P < .001), and have a lower body mass index (29 kg/m2 vs 30 kg/m2; P < .001). IBD patients with (odds ratio, 4.60; 95% confidence interval, 3.93-5.37) and without (odds ratio, 1.77; 95% confidence interval, 1.42-2.21) steroid use had a significantly higher risk of osteoporosis or osteopenia. Twenty-one IBD variants associated with reduced bone mineral density at Pâ ≤â .05 and 3 IBD risk variants associated with reduced bone mineral density at P ≤ 5 × 10-8. Of the 3 genome-wide significant variants, 2 increased risk of IBD (rs12568930-T MIR4418;ZBTB40; rs7236492-C NFATC1). MR did not reveal a causal effect of genetically predicted IBD on bone density (MR Egger, Pâ =â .30; inverse variance weighted, Pâ =â .63).CONCLUSIONS:
Patients with IBD are at increased risk for low bone density, independent of steroid use. Variants in or near ZBTB40 and NFATC1 are associated with an increased risk of IBD and low bone density.
Patients with inflammatory bowel disease (IBD) are at an increased risk of osteopenia, osteoporosis, and bone fracture. Herein, we identify risk variants in or near ZBTB40 and NFATC1 which associate with risk of both IBD and low bone density. Therefore, a subset of patients with IBD may be at risk for osteopenia and osteoporosis regardless of steroid use.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Osteoporosis
/
Bone Diseases, Metabolic
/
Inflammatory Bowel Diseases
Type of study:
Clinical_trials
/
Etiology_studies
/
Prognostic_studies
/
Risk_factors_studies
Limits:
Female
/
Humans
/
Middle aged
Language:
En
Journal:
Inflamm Bowel Dis
Journal subject:
GASTROENTEROLOGIA
Year:
2023
Document type:
Article
Affiliation country:
Estados Unidos