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Vitamin D and risk of pregnancy related hypertensive disorders: mendelian randomisation study.
BMJ. 2018 06 20; 361:k2167.BMJ

Abstract

OBJECTIVE

To use mendelian randomisation to investigate whether 25-hydroxyvitamin D concentration has a causal effect on gestational hypertension or pre-eclampsia.

DESIGN

One and two sample mendelian randomisation analyses.

SETTING

Two European pregnancy cohorts (Avon Longitudinal Study of Parents and Children, and Generation R Study), and two case-control studies (subgroup nested within the Norwegian Mother and Child Cohort Study, and the UK Genetics of Pre-eclampsia Study).

PARTICIPANTS

7389 women in a one sample mendelian randomisation analysis (751 with gestational hypertension and 135 with pre-eclampsia), and 3388 pre-eclampsia cases and 6059 controls in a two sample mendelian randomisation analysis.

EXPOSURES

Single nucleotide polymorphisms in genes associated with vitamin D synthesis (rs10741657 and rs12785878) and metabolism (rs6013897 and rs2282679) were used as instrumental variables.

MAIN OUTCOME MEASURES

Gestational hypertension and pre-eclampsia defined according to the International Society for the Study of Hypertension in Pregnancy.

RESULTS

In the conventional multivariable analysis, the relative risk for pre-eclampsia was 1.03 (95% confidence interval 1.00 to 1.07) per 10% decrease in 25-hydroxyvitamin D level, and 2.04 (1.02 to 4.07) for 25-hydroxyvitamin D levels <25 nmol/L compared with ≥75 nmol/L. No association was found for gestational hypertension. The one sample mendelian randomisation analysis using the total genetic risk score as an instrument did not provide strong evidence of a linear effect of 25-hydroxyvitamin D on the risk of gestational hypertension or pre-eclampsia: odds ratio 0.90 (95% confidence interval 0.78 to 1.03) and 1.19 (0.92 to 1.52) per 10% decrease, respectively. The two sample mendelian randomisation estimate gave an odds ratio for pre-eclampsia of 0.98 (0.89 to 1.07) per 10% decrease in 25-hydroxyvitamin D level, an odds ratio of 0.96 (0.80 to 1.15) per unit increase in the log(odds) of 25-hydroxyvitamin D level <75 nmol/L, and an odds ratio of 0.93 (0.73 to 1.19) per unit increase in the log(odds) of 25-hydroxyvitamin D levels <50 nmol/L.

CONCLUSIONS

No strong evidence was found to support a causal effect of vitamin D status on gestational hypertension or pre-eclampsia. Future mendelian randomisation studies with a larger number of women with pre-eclampsia or more genetic instruments that would increase the proportion of 25-hydroxyvitamin D levels explained by the instrument are needed.

Authors+Show Affiliations

Medical Research Council Integrative Epidemiology Unit, University of Bristol, Bristol BS8 2BN, UK Maria.Christine.Magnus@bristol.ac.uk. Department of Population Health Sciences, Bristol Medical School, Bristol, UK. Centre for Fertility and Health, Norwegian Institute of Public Health, Oslo, Norway.Generation R Study Group, Erasmus MC, University Medical Centre Rotterdam, Rotterdam, Netherlands. Department of Pediatrics, Erasmus MC, University Medical Centre Rotterdam, Rotterdam, Netherlands. Department of Epidemiology, Erasmus MC, University Medical Centre Rotterdam, Rotterdam, Netherlands.Gillings School of Global Public Health, University of North Carolina, Chapel Hill, NC, USA.Gillings School of Global Public Health, University of North Carolina, Chapel Hill, NC, USA.Generation R Study Group, Erasmus MC, University Medical Centre Rotterdam, Rotterdam, Netherlands. Department of Pediatrics, Erasmus MC, University Medical Centre Rotterdam, Rotterdam, Netherlands. Department of Epidemiology, Erasmus MC, University Medical Centre Rotterdam, Rotterdam, Netherlands.Generation R Study Group, Erasmus MC, University Medical Centre Rotterdam, Rotterdam, Netherlands. Department of Pediatrics, Erasmus MC, University Medical Centre Rotterdam, Rotterdam, Netherlands. Department of Epidemiology, Erasmus MC, University Medical Centre Rotterdam, Rotterdam, Netherlands.Medical Research Council Integrative Epidemiology Unit, University of Bristol, Bristol BS8 2BN, UK. Department of Population Health Sciences, Bristol Medical School, Bristol, UK. National Institute for Health Research Bristol Biomedical Research Centre, University Hospitals Bristol NHS Foundation Trust, and the University of Bristol, Bristol, UK.Epidemiology Branch, National Institute of Environmental Health Sciences, National Institutes of Health, Department of Health and Human Services, Research Triangle Park, NC, USA.Centre for Fertility and Health, Norwegian Institute of Public Health, Oslo, Norway Maria.Christine.Magnus@bristol.ac.uk.Sanger Institute, University of Cambridge, Cambridge, UK.Division for Mental and Physical Health, Norwegian Institute of Public Health, Oslo, Norway.Division for Mental and Physical Health, Norwegian Institute of Public Health, Oslo, Norway. Oslo Centre for Biostatistics and Epidemiology, Oslo University Hospital, Oslo, Norway.Generation R Study Group, Erasmus MC, University Medical Centre Rotterdam, Rotterdam, Netherlands. Department of Epidemiology, Erasmus MC, University Medical Centre Rotterdam, Rotterdam, Netherlands. Department of Internal Medicine, Erasmus MC, University Medical Centre Rotterdam, Rotterdam, Netherlands.Division for Mental and Physical Health, Norwegian Institute of Public Health, Oslo, Norway.Division for Mental and Physical Health, Norwegian Institute of Public Health, Oslo, Norway.Sanger Institute, University of Cambridge, Cambridge, UK.Medical Research Council Integrative Epidemiology Unit, University of Bristol, Bristol BS8 2BN, UK. Department of Population Health Sciences, Bristol Medical School, Bristol, UK. Departamento de Medicina Preventiva, Faculdade de Medicina, Universidade de São Paulo, São Paulo, Brazil.Medical Research Council Integrative Epidemiology Unit, University of Bristol, Bristol BS8 2BN, UK. Department of Population Health Sciences, Bristol Medical School, Bristol, UK. National Institute for Health Research Bristol Biomedical Research Centre, University Hospitals Bristol NHS Foundation Trust, and the University of Bristol, Bristol, UK.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

29925546

Citation

Magnus, Maria C., et al. "Vitamin D and Risk of Pregnancy Related Hypertensive Disorders: Mendelian Randomisation Study." BMJ (Clinical Research Ed.), vol. 361, 2018, pp. k2167.
Magnus MC, Miliku K, Bauer A, et al. Vitamin D and risk of pregnancy related hypertensive disorders: mendelian randomisation study. BMJ. 2018;361:k2167.
Magnus, M. C., Miliku, K., Bauer, A., Engel, S. M., Felix, J. F., Jaddoe, V. W. V., Lawlor, D. A., London, S. J., Magnus, P., McGinnis, R., Nystad, W., Page, C. M., Rivadeneira, F., Stene, L. C., Tapia, G., Williams, N., Bonilla, C., & Fraser, A. (2018). Vitamin D and risk of pregnancy related hypertensive disorders: mendelian randomisation study. BMJ (Clinical Research Ed.), 361, k2167. https://doi.org/10.1136/bmj.k2167
Magnus MC, et al. Vitamin D and Risk of Pregnancy Related Hypertensive Disorders: Mendelian Randomisation Study. BMJ. 2018 06 20;361:k2167. PubMed PMID: 29925546.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Vitamin D and risk of pregnancy related hypertensive disorders: mendelian randomisation study. AU - Magnus,Maria C, AU - Miliku,Kozeta, AU - Bauer,Anna, AU - Engel,Stephanie M, AU - Felix,Janine F, AU - Jaddoe,Vincent W V, AU - Lawlor,Debbie A, AU - London,Stephanie J, AU - Magnus,Per, AU - McGinnis,Ralph, AU - Nystad,Wenche, AU - Page,Christian M, AU - Rivadeneira,Fernando, AU - Stene,Lars C, AU - Tapia,German, AU - Williams,Nicholas, AU - Bonilla,Carolina, AU - Fraser,Abigail, Y1 - 2018/06/20/ PY - 2018/6/22/entrez PY - 2018/6/22/pubmed PY - 2019/3/6/medline SP - k2167 EP - k2167 JF - BMJ (Clinical research ed.) JO - BMJ VL - 361 N2 - OBJECTIVE: To use mendelian randomisation to investigate whether 25-hydroxyvitamin D concentration has a causal effect on gestational hypertension or pre-eclampsia. DESIGN: One and two sample mendelian randomisation analyses. SETTING: Two European pregnancy cohorts (Avon Longitudinal Study of Parents and Children, and Generation R Study), and two case-control studies (subgroup nested within the Norwegian Mother and Child Cohort Study, and the UK Genetics of Pre-eclampsia Study). PARTICIPANTS: 7389 women in a one sample mendelian randomisation analysis (751 with gestational hypertension and 135 with pre-eclampsia), and 3388 pre-eclampsia cases and 6059 controls in a two sample mendelian randomisation analysis. EXPOSURES: Single nucleotide polymorphisms in genes associated with vitamin D synthesis (rs10741657 and rs12785878) and metabolism (rs6013897 and rs2282679) were used as instrumental variables. MAIN OUTCOME MEASURES: Gestational hypertension and pre-eclampsia defined according to the International Society for the Study of Hypertension in Pregnancy. RESULTS: In the conventional multivariable analysis, the relative risk for pre-eclampsia was 1.03 (95% confidence interval 1.00 to 1.07) per 10% decrease in 25-hydroxyvitamin D level, and 2.04 (1.02 to 4.07) for 25-hydroxyvitamin D levels <25 nmol/L compared with ≥75 nmol/L. No association was found for gestational hypertension. The one sample mendelian randomisation analysis using the total genetic risk score as an instrument did not provide strong evidence of a linear effect of 25-hydroxyvitamin D on the risk of gestational hypertension or pre-eclampsia: odds ratio 0.90 (95% confidence interval 0.78 to 1.03) and 1.19 (0.92 to 1.52) per 10% decrease, respectively. The two sample mendelian randomisation estimate gave an odds ratio for pre-eclampsia of 0.98 (0.89 to 1.07) per 10% decrease in 25-hydroxyvitamin D level, an odds ratio of 0.96 (0.80 to 1.15) per unit increase in the log(odds) of 25-hydroxyvitamin D level <75 nmol/L, and an odds ratio of 0.93 (0.73 to 1.19) per unit increase in the log(odds) of 25-hydroxyvitamin D levels <50 nmol/L. CONCLUSIONS: No strong evidence was found to support a causal effect of vitamin D status on gestational hypertension or pre-eclampsia. Future mendelian randomisation studies with a larger number of women with pre-eclampsia or more genetic instruments that would increase the proportion of 25-hydroxyvitamin D levels explained by the instrument are needed. SN - 1756-1833 UR - https://www.unboundmedicine.com/medline/citation/29925546/Vitamin_D_and_risk_of_pregnancy_related_hypertensive_disorders:_mendelian_randomisation_study_ L2 - http://www.bmj.com/cgi/pmidlookup?view=long&amp;pmid=29925546 DB - PRIME DP - Unbound Medicine ER -