title: Vitamin D and mortality: a Mendelian randomization study.
abstract: BACKGROUND
  Decreased circulating 25-hydroxy-vitamin D (25-OH-vitamin D) concentrations have been associated with mortality rates, but it is unclear whether this association is causal. We performed a Mendelian randomization study and analyzed whether 3 common single-nucleotide polymorphisms (SNPs) associated with 25-OH-vitamin D concentrations are causal for mortality rates.
  
  
  METHODS
  Genotypes of SNPs in the group-specific component gene (GC, rs2282679), 7-dehydrocholesterol reductase gene (DHCR7, rs12785878), and cytochrome P450 IIR-1 gene (CYP2R1, rs10741657) were determined in a prospective cohort study of 3316 male and female participants [mean age 62.6 (10.6) years] scheduled for coronary angiography between 1997 and 2000. 25-OH-vitamin D concentrations were determined by RIA. The main outcome measures were all-cause deaths, cardiovascular deaths, and noncardiovascular deaths.
  
  
  RESULTS
  In a linear regression model adjusting for month of blood sampling, age, and sex, vitamin D concentrations were predicted by GC genotype (P < 0.001), CYP2R1 genotype (P = 0.068), and DHCR7 genotype (P < 0.001), with a coefficient of determination (r(2)) of 0.175. During a median follow-up time of 9.9 years, 955 persons (30.0%) died, including 619 deaths from cardiovascular causes. In a multivariate Cox regression adjusted for classical risk factors, GC, CYP2R1, and DHCR7 genotypes were not associated with all-cause mortality, cardiovascular mortality, or noncardiovascular mortality.
  
  
  CONCLUSIONS
  Genetic variants associated with 25-OH-vitamin D concentrations do not predict mortality. This suggests that low 25-OH-vitamin D concentrations are associated with, but unlikely to be causal for, higher mortality rates.
authors: Division of Endocrinology and Metabolism, Department of Internal Medicine, Medical University of Graz, Graz, Austria.
authors: Olivia
authors: O
authors: Trummer
authors: Stefan
authors: S
authors: Pilz
authors: Michael M
authors: MM
authors: Hoffmann
authors: Bernhard R
authors: BR
authors: Winkelmann
authors: Bernhard O
authors: BO
authors: Boehm
authors: Winfried
authors: W
authors: März
authors: Thomas R
authors: TR
authors: Pieber
authors: Barbara
authors: B
authors: Obermayer-Pietsch
authors: Wilfried
authors: W
authors: Renner
mesh_terms: D002318:Cardiovascular Diseases / Q000097:blood / Q000235:genetics / Q000401:mortality*; D053493:Cholestanetriol 26-Monooxygenase / Q000235:genetics; D015331:Cohort Studies; D000072467:Cytochrome P450 Family 2; D005260:Female; D005500:Follow-Up Studies; D005787:Gene Frequency; D006801:Humans; D016014:Linear Models; D008297:Male; D057182:Mendelian Randomization Analysis; D008875:Middle Aged; D044925:Oxidoreductases Acting on CH-CH Group Donors / Q000235:genetics; D020641:Polymorphism, Single Nucleotide; D016016:Proportional Hazards Models; D011446:Prospective Studies; D014807:Vitamin D / Q000031:analogs & derivatives* / Q000097:blood; D014808:Vitamin D Deficiency / Q000097:blood / Q000235:genetics / Q000401:mortality*; D014809:Vitamin D-Binding Protein / Q000235:genetics
chemical_list: D014809:Vitamin D-Binding Protein; D014807:Vitamin D; C104450:25-hydroxyvitamin D; D000072467:Cytochrome P450 Family 2; C506833:CYP2R1 protein, human; D053493:Cholestanetriol 26-Monooxygenase; D044925:Oxidoreductases Acting on CH-CH Group Donors; C019995:7-dehydrocholesterol reductase