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Sci Rep. 2017 Oct 16;7(1):13230. doi: 10.1038/s41598-017-13189-3.

Vitamin D and cognitive function: A Mendelian randomisation study.

Author information

1
MRC Lifelong Health and Ageing at UCL, London, United Kingdom. jane.maddock@ucl.ac.uk.
2
Population, Policy and Practice, UCL Great Ormond Street Institute of Child Health, London, United Kingdom. jane.maddock@ucl.ac.uk.
3
Centre for Population Health Research, Sansom Institute, University of South Australia, Adelaide, Australia.
4
Population, Policy and Practice, UCL Great Ormond Street Institute of Child Health, London, United Kingdom.
5
Wolfson Institute of Preventive Medicine, Queen Mary University of London, London, United Kingdom.
6
University of Exeter Medical School, Exeter, United Kingdom.
7
Institute for Social and Economic Research (ISER), University of Essex, Colchester, United Kingdom.
8
Division of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ), Heidelberg, Germany.
9
Network Aging Research (NAR), University of Heidelberg, Heidelberg, Germany.
10
Institute of Health Care and Social Sciences, FOM University, Essen, Germany.
11
Department of Epidemiology and Public Health, University College London, London, United Kingdom.
12
Division of Internal Medicine, University Hospital of North Norway, Tromsø, Norway.
13
Endocrinology Research Group, Department of Clinical Medicine, Faculty of Health Sciences, UiT The Arctic University of Norway, Tromsø, Norway.
14
Center for Life Course Health Research, University of Oulu, Oulu, Finland.
15
Oulu University Hospital, Oulu, Finland.
16
Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
17
Department of Clinical Chemistry, Fimlab Laboratories and Faculty of Medicine and Life Sciences, University of Tampere, Tampere, Finland.
18
Research Centre of Applied and Preventive Cardiovascular Medicine, University of Turku, Turku, Finland.
19
Department of Surgical Sciences, Uppsala University, Uppsala, Sweden.
20
Department of Psychology and Logopedics, University of Helsinki, Helsinki, Finland.
21
Helsinki Collegium for Advanced Studies, University of Helsinki, Helsinki, Finland.
22
Department of Medicine, Internal Medicine, Lausanne University Hospital, Lausanne, Switzerland.
23
Department of Public Health and Nursing, Faculty of Medicine and Health Sciences, Norwegian University of Science and Technology (NTNU), Trondheim, Norway.
24
Department of Clinical Medicine, Faculty of Health Sciences, UiT The Arctic University of Norway, Tromsø, Norway.
25
Department of Cardiology, Akershus University Hospital, Lørenskog, Norway.
26
INSERM, U1018, Centre for Research in Epidemiology and Population Health, Hôpital Paul Brousse, Villejuif, France.
27
Department of Pediatrics, Tampere University Hospital and Faculty of Medicine and Life Sciences, University of Tampere, Tampere, Finland.
28
Department of Clinical Physiology, Tampere University Hospital and Faculty  of Medicine and Life Sciences, University of Tampere, Tampere, Finland.
29
Department of Public Health and Caring Sciences, Uppsala University, Uppsala, Sweden.
30
Department of Medical Sciences, Uppsala University, Uppsala, Sweden.
31
Department of Medicine, Division of Cardiovascular Medicine, Stanford University School of Medicine, Stanford, California, USA.
32
Unit of Population Epidemiology, Division of Primary Care Medicine, Department of Community Medicine, Primary Care and Emergency Medicine, Geneva University Hospitals, Geneva, Switzerland.
33
Department of Epidemiology, Rollins School of Public Health, Emory University, Atlanta, Georgia, USA.
34
Department of Ambulatory Care and Community Medicine, University of Lausanne, Lausanne, Switzerland.
35
Division of General Neurology, Department of Neurology, General Hospital and Medical University of Graz, Graz, Austria.
36
Research Unit for Genetic Epidemiology, Institute of Molecular Biology and Biochemistry, Center of Molecular Medicine, Medical University of Graz, Graz, Austria.
37
Department of Neurology, Clinical Division of Neurogeriatrics, Medical University Graz, Graz, Austria.
38
Department of General Practice and Primary Health Care, University of Helsinki and Helsinki University Hospital, University of Helsinki, Helsinki, Finland.
39
Folkhälsan Research Center, Helsinki, Finland.
40
Department of Clinical Physiology and Nuclear Medicine, Turku University Hospital, Turku, Finland.
41
Research Unit of Biomedicine, University of Oulu, Oulu, Finland.
42
Biocenter Oulu, University of Oulu, Oulu, Finland.
43
Medical Research Center (MRC) and Oulu University Hospital, Oulu, Finland.
44
Department of Gastroenterology and Metabolism, Poznan University of Medical Sciences, Poznan, Poland.
45
Department of Epidemiology and Biostatistics, MRC-PHE Centre for Environment & Health, School of Public Health, Imperial College London, London, UK.
46
Research Unit of Clinical Neuroscience, Department of Psychiatry, University of Oulu, Oulu, Finland.
47
Department of Psychiatry, University Hospital of Oulu, Oulu, Finland.
48
Clinicum, University of Helsinki, Helsinki, Finland.
49
Population, Policy and Practice, UCL Great Ormond Street Institute of Child Health, London, United Kingdom. elina.hypponen@unisa.edu.au.
50
Centre for Population Health Research, Sansom Institute, University of South Australia, Adelaide, Australia. elina.hypponen@unisa.edu.au.
51
South Australian Health and Medical Research Institute, Adelaide, Australia. elina.hypponen@unisa.edu.au.

Abstract

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, p curvature ≤ 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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