The genetically predicted causal relationship of inflammatory bowel disease with bone mineral density and osteoporosis: evidence from two-sample Mendelian randomization

Abstract

BackgroundMany existing studies indicated that patients with inflammatory bowel disease (IBD), including ulcerative colitis (UC) and Crohn’s disease (CD), tend to have the risk of low total body bone mineral density (BMD), and are more likely to have osteoporosis (OS). To determine the causal relationship between IBD and bone metabolic disorders, we herein performed a two-sample Mendelian randomization analysis (TSMR) using publicly available summary statistics.MethodsSummary statistics of total body BMD, OS and IBD were downloaded from the Open Genome-Wide Association Study (GWAS), FinnGen consortium and International Inflammatory Bowel Disease Genetics Consortium (IIBDGC). The European and East Asian populations have consisted in this Mendelian Randomization (MR) work. A range of quality control procedures were taken to select eligible instrument SNPs closely associated with total body BMD, OS and IBD. To make the conclusions more reliable, we applied five robust analytical methods, among which the inverse variance weighting (IVW) method acted as the major method. Besides, heterogeneity, pleiotropy and sensitivity were evaluated.ResultsIn the European population, the genetic association of UC on total body BMD (OR=0.97, 95%CI=0.96,0.99, P<0.001) and overall IBD on total body BMD (OR=0.98, 95%CI=0.97,1.00, P=0.013) were significant, while the effect of CD on total body BMD was not significant enough (OR=0.99, 95%CI=0.98,1.00, P=0.085). All of UC, CD and overall IBD can be the genetic risk factor of having OS with pathological fracture (UC: OR=1.13, 95%CI=1.02,1.26, P=0.024, CD: OR=1.14, 95%CI=1.05,1.25, P=0.003, overall IBD: OR=1.13, 95%CI=1.02,1.24, P=0.015). In East Asian groups, only CD had a causal relationship with OS (OR=1.04, 95% CI=1.01,1.07, P=0.019).ConclusionOur study revealed genetically predicted associations between IBD on total body BMD and OS in European and East Asian populations. This work supplemented the results of previous retrospective studies and demonstrated the necessity of BMD monitoring in patients with IBD.

Identifying Crucial Biomarkers in Osteoporosis and Ulcerative Colitis Through Bioinformatics Analysis of Co-expressed Genes

“…The global prevalence of both OP and UC is on the rise, posing a significant socioeconomic burden and causing distress and strain on the lives of patients. Interestingly, OP has been identified as one of the common extraintestinal complications of UC [ 11 ]. The prevalence of osteoporosis among patients with UC is increasing.…”

Molecular and Cellular Mechanisms of Osteoporosis

“…The association of osteoporosis with chronic colitis and Crohn's disease was shown in a meta-analysis of 30 GWAS. The incidence of fractures in people with inflammatory bowel disease is 40% higher than in the general population [121].…”

Causal linkage between type 2 diabetes mellitus and inflammatory bowel disease: an integrated Mendelian randomization study and bioinformatics analysis

“…Referring to a previous study, IVs were screened through the following steps (1): Identification of SNPs closely related to exposure factors with a significance standard threshold of P<5×10 -8 ; (2) Elimination of SNPs in linkage disequilibrium with a standard of r 2 = 0.001 and kb=10,000; (3) Calculation of the F statistic (b 2 /SE 2 ) to assess weak IV bias. An F value below 10 indicates a weak IV bias, which might lead to an underestimation of statistical power (15); (4) Exclusion of IVs related to confounding such as obesity using PhenoScanner (http://www.phenoscanner.medschl.cam.ac.uk/), which provided SNP phenotyping information was employed. In instances where a disease corresponds to multiple sources of GWAS summary data, IVs were initially screened individually according to the Flow chart of the bidirectional MR study.…”