University of Oulu

Maddock, J., Zhou, A., Cavadino, A., Kuźma, E., Bao, Y., Smart, M., Saum, K., Schöttker, B., Engmann, J., Kjærgaard, M., Karhunen, V., Zhan, Y., Lehtimäki, T., Rovio, S., Byberg, L., Lahti, J., Marques-Vidal, P., Sen, A., Perna, L., Schirmer, H., Singh-Manoux, A., Auvinen, J., Hutri-Kähönen, N., Kähönen, M., Kilander, L., Räikkönen, K., Melhus, H., Ingelsson, E., Guessous, I., Petrovic, K., Schmidt, H., Schmidt, R., Vollenweider, P., Lind, L., Eriksson, J., Michaëlsson, K., Raitakari, O., Hägg, S., Pedersen, N., Herzig, K., Järvelin, M., Veijola, J., Kivimaki, M., Jorde, R., Brenner, H., Kumari, M., Power, C., Llewellyn, D., Hyppönen, E. (2017) Vitamin D and cognitive function: A Mendelian randomisation study. Scientific Reports, 7 (1). doi:10.1038/s41598-017-13189-3

Vitamin D and cognitive function : a Mendelian randomisation study

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Author: Maddock, Jane1,2; Zhou, Ang3; Cavadino, Alana2,4;
Organizations: 1MRC Lifelong Health and Ageing at UCL, London
2Population, Policy and Practice, UCL Great Ormond Street Institute of Child Health, London
3Centre for Population Health Research, Sansom Institute, University of South Australia
4Wolfson Institute of Preventive Medicine, Queen Mary University of London
5University of Exeter Medical School
6Institute for Social and Economic Research (ISER), University of Essex
7Division of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ)
8Network Aging Research (NAR), University of Heidelberg
9Institute of Health Care and Social Sciences, FOM University
10Department of Epidemiology and Public Health, University College London
11Division of Internal Medicine, University Hospital of North Norway
12Endocrinology Research Group, Department of Clinical Medicine, Faculty of Health Sciences, UiT The Arctic University of Norway
13Center for Life Course Health Research, University of Oulu
14Oulu University Hospital
15Department of Medical Epidemiology and Biostatistics, Karolinska Institutet
16Department of Clinical Chemistry, Fimlab Laboratories and Faculty of Medicine and Life Sciences, University of Tampere
17Research Centre of Applied and Preventive Cardiovascular Medicine, University of Turku
18Department of Surgical Sciences, Uppsala University
19Department of Psychology and Logopedics, University of Helsinki
20Helsinki Collegium for Advanced Studies, University of Helsinki
21Department of Medicine, Internal Medicine, Lausanne University Hospital
22Department of Public Health and Nursing, Faculty of Medicine and Health Sciences, Norwegian University of Science and Technology (NTNU)
23Department of Clinical Medicine, Faculty of Health Sciences, UiT The Arctic University of Norway
24Department of Cardiology, Akershus University Hospital
25INSERM, U1018, Centre for Research in Epidemiology and Population Health, Hôpital Paul Brousse
26Department of Pediatrics, Tampere University Hospital and Faculty of Medicine and Life Sciences, University of Tampere
27Department of Clinical Physiology, Tampere University Hospital and Faculty of Medicine and Life Sciences, University of Tampere
28Department of Public Health and Caring Sciences, Uppsala University
29Department of Medical Sciences, Uppsala University
30Department of Medicine, Division of Cardiovascular Medicine, Stanford University School of Medicine
31Unit of Population Epidemiology, Division of Primary Care Medicine, Department of Community Medicine, Primary Care and Emergency Medicine, Geneva University Hospitals
32Department of Epidemiology, Rollins School of Public Health, Emory University
33Department of Ambulatory Care and Community Medicine, University of Lausanne
34Division of General Neurology, Department of Neurology, General Hospital and Medical University of Graz
35Research Unit for Genetic Epidemiology, Institute of Molecular Biology and Biochemistry, Center of Molecular Medicine, Medical University of Graz
36Department of Neurology, Clinical Division of Neurogeriatrics, Medical University Graz
37Department of General Practice and Primary Health Care, University of Helsinki and Helsinki University Hospital, University of Helsinki
38Department of Clinical Physiology and Nuclear Medicine, Turku University Hospital
39Research Unit of Biomedicine, University of Oulu
40Biocenter Oulu, University of Oulu
41Medical Research Center (MRC) and Oulu University Hospital
42Department of Gastroenterology and Metabolism, Poznan University of Medical Sciences
43Department of Epidemiology and Biostatistics, MRC–PHE Centre for Environment & Health, School of Public Health, Imperial College London
44Research Unit of Clinical Neuroscience, Department of Psychiatry, University of Oulu
45Department of Psychiatry, University Hospital of Oulu
46Clinicum, University of Helsinki
47Population, Policy and Practice, UCL Great Ormond Street Institute of Child Health
48South Australian Health and Medical Research Institute
Format: article
Version: published version
Access: open
Online Access: PDF Full Text (PDF, 1.2 MB)
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Language: English
Published: Springer Nature, 2017
Publish Date: 2017-11-20


The causal nature of the association between hypovitaminosis D and poor cognitive function in mid- to later-life is uncertain. Using a Mendelian randomisation(MR) approach, we examined the causal relationship between 25(OH)D and cognitive function. Data came from 172,349 participants from 17 cohorts. DHCR7(rs12785878), CYP2R1 rs12794714) and their combined synthesis score were chosen to proxy 25(OH)D. Cognitive tests were standardised into global and memory scores. Analyses were stratified by 25(OH)D tertiles, sex and age. Random effects meta-analyses assessed associations between 25(OH)D and cognitive function. Associations of serum 25(OH)D with global and memory-related cognitive function were non-linear (lower cognitive scores for both low and high 25(OH)D, pcurvature ≤ 0.006), with much of the curvature attributed to a single study. DHCR7, CYP2R1, and the synthesis score were associated with small reductions in 25(OH)D per vitamin D-decreasing allele. However, coefficients for associations with global or memory-related cognitive function were non-significant and in opposing directions for DHCR7 and CYP2R1, with no overall association observed for the synthesis score. Coefficients for the synthesis score and global and memory cognition were similar when stratified by 25(OH)D tertiles, sex and age. We found no evidence for serum 25(OH)D concentration as a causal factor for cognitive performance in mid- to later life.

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Series: Scientific reports
ISSN: 2045-2322
ISSN-E: 2045-2322
ISSN-L: 2045-2322
Volume: 7
Issue: 1
Article number: 13230
DOI: 10.1038/s41598-017-13189-3
Type of Publication: A1 Journal article – refereed
Field of Science: 3142 Public health care science, environmental and occupational health
3112 Neurosciences
Funding: Primary project funding came from The Judith Jane Mason & Harold Stannett Williams Memorial Foundation, other resources are listed in the supplementary material.
Dataset Reference: Supplementary material:
Copyright information: © The Author(s) 2017. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder.