Generational Differences in The Age at Diagnosis With Ibd: Genetic Anticipation, Bias, Or Temporal Effects
Bibliographic record
Abstract
OBJECTIVE: Previous cross-sectional research has demonstrated generational differences in age at diagnosis (AAD) in inflammatory bowel disease (IBD). This observation has at times been ascribed to genetic anticipation, but could also be due to biases related to case ascertainment or follow-up or to temporal changes in IBD epidemiology. We aimed to explore this issue using a population-based database. METHODS: In 1995 we used the comprehensive administrative databases in the province of Manitoba, Canada to establish a population-based IBD Research Registry that includes clinical and demographic information for persons. We contacted those subjects within our Research Registry who reported having any family members with IBD and their family members for verification of diagnosis and AAD. Differences in AAD between familial pairs were calculated. In addition, to assess whether duration of follow-up accounted for generational differences in AAD, we computed the mean AAD for subjects with and without family histories of IBD based on age at the time of interview (i.e., < 45 and > or = 45 yr of age). RESULTS: Of the 2445 persons with IBD in the Research Registry, 548 reported positive family histories, and 315 of these (58%) were reached by telephone. There were 169 Crohn's disease and 146 ulcerative colitis subjects with positive family histories. The mean AADs for the parents, aunts/uncles, and grandparents were significantly greater than the mean AADs for the children, nieces/nephews, and grandchildren, respectively. There was a doubling of the mean AAD when comparing the grandparent/grandchild cases with the parent/child or aunt/uncle-niece/nephew cases. No statistically significant difference in anticipation was observed, whether or not the older generation was male or female or had Crohn's disease or ulcerative colitis. The AAD was substantially greater for those interviewed at > or = 45 yr of age for subjects with and without family histories. However, there was no substantial difference in mean AAD between familial and nonfamilial subjects. CONCLUSION: The present study has demonstrated that there is a tendency for children to be younger than their parents at the time of diagnosis of familial IBD, and that this difference in mean AAD is almost doubled for grandparent/grandchild pairs. However, we conclude that these differences are most likely due to a bias based on length of follow-up or recent multigenerational temporal changes in the risk of IBD, or both.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.021 | 0.060 |
| Meta-epidemiology (narrow) | 0.001 | 0.001 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.001 | 0.002 |
| Science and technology studies | 0.001 | 0.001 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.001 | 0.001 |
| Research integrity | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.002 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".