Investigating the causal effect of vitamin D on serum adiponectin using a Mendelian randomization approach.
OBJECTIVE
The aim was to examine the causal effect of vitamin D on serum adiponectin using a multiple instrument Mendelian randomization approach.


METHODS
Serum 25-hydroxy vitamin D (25(OH)D) and serum total or high molecular weight (HMW) adiponectin were measured in two Danish population-based studies: the Inter99 study (6405 adults, 30-60 years) conducted in 1999-2001, and the MONICA10 study (2656 adults, 41-71 years) conducted in 1993-1994.


RESULTS
In the Inter99 study, serum 25(OH)D was positively associated with total adiponectin (the effect estimate in % per doubling of 25(OH)D was 4.78, 95% CI: 1.96, 7.68, P<0.001). Using variations in the vitamin D-binding protein gene and the filaggrin gene as instrumental variables, the causal effect in % was estimated to 61.46, 95% CI: 17.51, 120.28, P=0.003 higher adiponectin per doubling of 25(OH)D. In the MONICA10 cohort, no significant association was observed between the serum concentrations of 25(OH)D and HMW adiponectin (the effect estimate in % per doubling of 25(OH)D was -1.51, 95% CI: -5.80, 2.98, P=0.50), although the instrumental variables analysis to some extent supported a positive causal association (the effect estimate in % per doubling of 25(OH)D was 37.13, 95% CI: -3.67, 95.20, P=0.080).


CONCLUSIONS
The results indicate a possible causal association between serum 25(OH)D and total adiponectin. However, the association was not replicated for HMW adiponectin. Thus, further studies are needed to confirm a causal relationship.
Research Centre for Prevention and Health, Copenhagen University Hospital Glostrup, Glostrup, Denmark.
L L N
LL
Husemoen
Research Centre for Prevention and Health, Copenhagen University Hospital Glostrup, Glostrup, Denmark.
T
T
Skaaby
Department of Biostatistics, University of Copenhagen, Copenhagen, Denmark.
T
T
Martinussen
1] Research Centre for Prevention and Health, Copenhagen University Hospital Glostrup, Glostrup, Denmark [2] Faculty of Health Science, University of Copenhagen, Copenhagen, Denmark.
T
T
Jørgensen
Research Centre for Prevention and Health, Copenhagen University Hospital Glostrup, Glostrup, Denmark.
B H
BH
Thuesen
Department of Cardiology and Endocrinology, Copenhagen University Hospital Frederiksberg, Frederiksberg, Denmark.
C
C
Kistorp
1] Faculty of Health Science, University of Copenhagen, Copenhagen, Denmark [2] Department of Medicine M, Copenhagen University Hospital Glostrup, Glostrup, Denmark.
J
J
Jeppesen
National Allergy Research Centre, Department of Dermato Allergology, Copenhagen University Hospital Gentofte, Hellerup, Denmark.
J P
JP
Thyssen
Department of Clinical Biochemistry, Copenhagen University Hospital Gentofte, Hellerup, Denmark.
M
M
Meldgaard
Department of Clinical Biochemistry, Copenhagen University Hospital Gentofte, Hellerup, Denmark.
P B
PB
Szecsi
Department of Clinical Biochemistry, Copenhagen University Hospital Hvidovre, Hvidovre, Denmark.
M
M
Fenger
Research Centre for Prevention and Health, Copenhagen University Hospital Glostrup, Glostrup, Denmark.
A
A
Linneberg
D052242:Adiponectin / Q000097:blood*; D000328:Adult; D000368:Aged; D000886:Anthropometry; D003718:Denmark; D005260:Female; D000091344:Filaggrin Proteins; D014644:Genetic Variation; D005838:Genotype; D006801:Humans; D007055:Iceland; D007381:Intermediate Filament Proteins / Q000235:genetics; D008297:Male; D057182:Mendelian Randomization Analysis; D008875:Middle Aged; D008970:Molecular Weight; D009664:Norway; D013548:Sweden; D014807:Vitamin D / Q000031:analogs & derivatives* / Q000097:blood / Q000235:genetics; D014809:Vitamin D-Binding Protein / Q000235:genetics
D052242:Adiponectin; C000717249:FLG protein, human; D000091344:Filaggrin Proteins; D007381:Intermediate Filament Proteins; D014809:Vitamin D-Binding Protein; D014807:Vitamin D; C104450:25-hydroxyvitamin D