 Solution

The supplementary excerpt uses an adjusted observational study and a two-sample Mendelian randomization analysis.

The observational study examines co-occurrence of hypercalcaemia and migraine diagnoses in electronic health records, adjusting for age, sex, and ancestry. Its adjusted odds ratio is 1.58, with $P=4.75\times 10^{-13}$.

The two-sample Mendelian randomization analysis combines the associations of eight genetic variants with serum calcium and with migraine, using a weighted genetic risk score. It estimates an odds ratio of 1.80 per genetically predicted 1 mg/dL higher serum calcium, with 95% confidence interval $(1.31,2.46)$. The weighted-median Mendelian randomization estimator and MR-Egger regression provide sensitivity analyses.

The measured and instrumented exposure is serum calcium, rather than dietary calcium intake itself. Calcium intake and serum calcium are not interchangeable interventions, and an odds ratio of 1.80 is an odds contrast rather than necessarily an 80% increase in probability. The shortened excerpt supplies two approaches; a further analysis in the full research paper is outside this excerpt.