Genetic predisposition to increased serum calcium, bone mineral density, and fracture risk in individuals with normal calcium levels: mendelian randomisation study
Bibliographic record
Abstract
OBJECTIVE: To determine if genetically increased serum calcium levels are associated with improved bone mineral density and a reduction in osteoporotic fractures. DESIGN: Mendelian randomisation study. SETTING: Cohorts used included: the UK Biobank cohort, providing genotypic and estimated bone mineral density data; 25 cohorts from UK, USA, Europe, and China, providing genotypic and fracture data; and 17 cohorts from Europe, providing genotypic and serum calcium data (summary level statistics). PARTICIPANTS: A genome-wide association meta-analysis of serum calcium levels in up to 61 079 individuals was used to identify genetic determinants of serum calcium levels. The UK Biobank study was used to assess the association of genetic predisposition to increased serum calcium with estimated bone mineral density derived from heel ultrasound in 426 824 individuals who had, on average, calcium levels in the normal range. A fracture genome-wide association meta-analysis comprising 24 cohorts and the UK Biobank including a total of 76 549 cases and 470 164 controls, who, on average, also had calcium levels in the normal range was then performed. RESULTS: , 95% confidence interval -0.059 to 0.066; P=0.92) or a reduced risk of fractures (odds ratio 1.01, 95% confidence interval 0.89 to 1.15; P=0.85) in inverse-variance weighted mendelian randomisation analyses. Sensitivity analyses did not provide evidence of pleiotropic effects. CONCLUSIONS: Genetic predisposition to increased serum calcium levels in individuals with normal calcium levels is not associated with an increase in estimated bone mineral density and does not provide clinically relevant protection against fracture. Whether such predisposition mimics the effect of short term calcium supplementation is not known. Given that the same genetically derived increase in serum calcium is associated with an increased risk of coronary artery disease, widespread calcium supplementation in the general population could provide more risk than benefit.
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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 | 0.018 | 0.052 |
| Meta-epidemiology (narrow) | 0.002 | 0.001 |
| Meta-epidemiology (broad) | 0.002 | 0.003 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.001 | 0.001 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.001 | 0.001 |
| Research integrity | 0.002 | 0.001 |
| Insufficient payload (model declined to judge) | 0.003 | 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".