Introduction
Methods
Study cohort
Microarray genotyping and quality control
Genotype data
Estimation of population structure
Imputed expression levels of RBPMS gene
Statistical analysis
Phenotypic association analyses
Genome-wide association analysis
PRS association analysis of PC status in persons with IBD
Application of PRS to predict PC status in persons with IBD
Causal mediation analysis
Sensitivity analysis
Results
Demographic analysis
N = 240 | IBD without PC (N = 146) | IBD with PC (N = 94) | P-valuea |
---|---|---|---|
Sex | 0.054 | ||
Male | 71 (48.6%b) | 33 (35.1%) | |
Female | 75 (51.4%) | 61 (64.9%) | |
Age at diagnosis | 0.4564 | ||
16 years and under | 9 (6.16%) | 3 (3.2%) | |
17 to 40 years | 84 (57.5%) | 60 (63.8%) | |
Over 40 years | 53 (36.3%) | 31 (33.0%) | |
Disease subtype | 0.444 | ||
Crohn’s disease | 69 (47.3%) | 50 (53.2%) | |
Ulcerative colitis | 77 (52.7%) | 44 (46.8%) | |
Marital status | |||
Married/common-law | 106 (72.6%) | 66 (70.2%) | 0.799 |
Single/divorced/widowed | 40 (27.4%) | 28 (29.8%) |
Genome-wide association analysis
PRS association analysis of PC status in persons with IBD
P-value threshold | Number of significant SNPs identified from GWAS under the threshold | Number of SNPs after LD pruning | Number of SNPs mapped to external IBD GWAS and used in the PRS calculation | |
---|---|---|---|---|
1 | 5 × 10–2 | 63,590 | 21,748 | 9620 |
2 | 5 × 10–3 | 5501 | 1104 | 471 |
3 | 5 × 10–4 | 442 | 72 | 33 |
P-value threshold | Log OR | SE | P-value | R2a | |
---|---|---|---|---|---|
PCb ~ PRS | 5 × 10–2 | 0.07 | 0.13 | 6.17E−01 | 0.001 |
5 × 10–3 | 0.65 | 0.15 | 1.86E−05*** | 0.065 | |
5 × 10–4 | 0.61 | 0.15 | 3.64E−05*** | 0.059 | |
PC ~ PRS + sex + age + marital status + disease subtypes | 5 × 10–2 | 0.06 | 0.14 | 6.41E−01 | 0.023 |
5 × 10–3 | 0.69 | 0.16 | 1.46E−05*** | 0.090 | |
5 × 10–4 | 0.67 | 0.15 | 1.50E−05*** | 0.089 |