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Potential causal associations of serum 25-hydroxyvitamin D with lipids: a Mendelian randomization approach of the HUNT study

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journal contribution
posted on 27.03.2019, 14:00 by X-M Mai, V Videm, NA Sheehan, Y Chen, A Langhammer, Y-Q Sun
Observational studies have shown consistent associations between higher circulating 25-hydroxyvitamin D [25(OH)D] levels and favorable serum lipids. We sought to investigate if such associations were causal. A Mendelian randomization (MR) study was conducted on a population-based cohort comprising 56,435 adults in Norway. A weighted 25(OH)D allele score was generated based on vitamin D-increasing alleles of rs2282679, rs12785878 and rs10741657. Linear regression analyses of serum lipid levels on the allele score were performed to assess the presence of causal associations of serum 25(OH)D with the lipids. To quantify the causal effects, the inverse-variance weighted method was used for calculating MR estimates based on summarized data of individual single-nucleotide polymorphisms. The MR estimate with 95% confidence interval (CI) represents percentage difference in the lipid level per genetically determined 25 nmol/L increase in 25(OH)D. The 25(OH)D allele score demonstrated a clear association with high-density lipoprotein (HDL) cholesterol (p = 0.007) but no association with total or non-HDL cholesterol or triglycerides (p ≥ 0.27). The MR estimate showed 2.52% (95% CI 0.79-4.25%) increase in HDL cholesterol per genetically determined 25 nmol/L increase in 25(OH)D, which was stronger than the corresponding estimate of 1.83% (95% CI 0.85-2.81%) from the observational analysis. The MR estimates for total cholesterol (0.60%, 95% CI - 0.73 to 1.94%), non-HDL cholesterol (0.04%, 95% CI - 1.79 to 1.88%) and triglycerides (- 2.74%, 95% CI - 6.16 to 0.67%) showed no associations. MR analysis of data from a population-based cohort suggested a causal and positive association between serum 25(OH)D and HDL cholesterol.

Funding

The Nord-Trøndelag Health Study (HUNT) is a collaboration between the HUNT Research Centre (Faculty of Medicine and Health Sciences, NTNU—Norwegian University of Science and Technology), the Nord-Trøndelag County Council, and the Norwegian Institute of Public Health.

History

Citation

Eur J Epidemiol, 2019, 34 (1), pp. 57-66

Author affiliation

/Organisation/COLLEGE OF LIFE SCIENCES/School of Medicine/Department of Health Sciences

Version

AM (Accepted Manuscript)

Published in

Eur J Epidemiol

Publisher

Springer

eissn

1573-7284

Acceptance date

16/11/2018

Copyright date

2018

Publisher version

https://link.springer.com/article/10.1007/s10654-018-0465-x

Notes

The file associated with this record is under embargo until 12 months after publication, in accordance with the publisher's self-archiving policy. The full text may be available through the publisher links provided above.

Language

en