Estimating dose-response relationships for vitamin D with coronary heart disease, stroke, and all-cause mortality: observational and Mendelian randomisation analyses.

In sensitivity analyses excluding variants from each gene region in turn ( appendix p 20 ), the association with all-cause mortality in the deficient stratum was attenuated, but remained nominally significant when excluding variants in the CYP2R1 gene region from the analysis (OR 0·80 [95% CI 0·66–0·98]; p=0·027).

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In Mendelian randomisation analyses for a finer stratification of 25(OH)D concentrations, the doseresponse curve for all-cause mortality has a clear threshold shape with evidence of an inverse association at 25(OH)D concentrations below 40 nmol/L, and null associations above 40 nmol/L ( figure 4 ; appendix p 33 ); there was a notable trend in estimates below 40 nmol/L, with stronger inverse associations observed at lower 25(OH)D concentrations.

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