The association between neonatal vitamin D status and risk of schizophrenia

Darryl W. Eyles; Maciej Trzaskowski; Anna A.E. Vinkhuyzen; Manuel Mattheisen; Sandra Meier; Helen Gooch; Victor Anggono; Xiaoying Cui; Men Chee Tan; Thomas H.J. Burne; Se Eun Jang; David Kvaskoff; David M. Hougaard; Bent Nørgaard-Pedersen; Arieh Cohen; Esben Agerbo; Carsten B. Pedersen; Anders D. Børglum; Ole Mors; Pankaj Sah; Naomi R. Wray; Preben B. Mortensen; John J. McGrath

doi:10.1038/s41598-018-35418-z

The association between neonatal vitamin D status and risk of schizophrenia

Darryl W. Eyles, Maciej Trzaskowski, Anna A.E. Vinkhuyzen, Manuel Mattheisen, Sandra Meier, Helen Gooch, Victor Anggono, Xiaoying Cui, Men Chee Tan, Thomas H.J. Burne, Se Eun Jang, David Kvaskoff, David M. Hougaard, Bent Nørgaard-Pedersen, Arieh Cohen, Esben Agerbo, Carsten B. Pedersen, Anders D. Børglum, Ole Mors, Pankaj SahNaomi R. Wray, Preben B. Mortensen, John J. McGrath

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Resumen

Clues from the epidemiology of schizophrenia, such as the increased risk in those born in winter/spring, have led to the hypothesis that prenatal vitamin D deficiency may increase the risk of later schizophrenia. We wish to explore this hypothesis in a large Danish case-control study (n = 2602). The concentration of 25 hydroxyvitamin D (25OHD) was assessed from neonatal dried blood samples. Incidence rate ratios (IRR) were calculated when examined for quintiles of 25OHD concentration. In addition, we examined statistical models that combined 25OHD concentration and the schizophrenia polygenic risk score (PRS) in a sample that combined the new sample with a previous study (total n = 3464; samples assayed and genotyped between 2008-2013). Compared to the reference (fourth) quintile, those in the lowest quintile (<20.4 nmol/L) had a significantly increased risk of schizophrenia (IRR = 1.44, 95%CI: 1.12–1.85). None of the other quintile comparisons were significantly different. There was no significant interaction between 25OHD and the PRS. Neonatal vitamin D deficiency was associated with an increased risk for schizophrenia in later life. These findings could have important public health implications related to the primary prevention of schizophrenia.

Idioma original	English
Número de artículo	17692
Publicación	Scientific Reports
Volumen	8
N.º	1
DOI	https://doi.org/10.1038/s41598-018-35418-z
Estado	Published - dic. 1 2018
Publicado de forma externa	Sí

Nota bibliográfica

Funding Information:
We thank Peter Josh, Henry Simila and Pauline Ko for assistance with vitamin D assays, and Gavin Bird and Karin Bird for general support related to this field of research. This project was supported by NHMRC Project grants (APP 1007677, APP 1099709) and a John Cade Fellowship (APP1056929). JM was supported by a Niels Bohr Professorship from the Danish National Research Foundation. This study was supported by the Lundbeck Foundation (grant no R102-A9118 and R155-2014-1724), Denmark; the Stanley Medical Research Institute; an Advanced Grant from the European Research Council (project no: 294838); the Stanley Center for Psychiatric Research at Broad Institute and Centre for Integrated Register-based Research at Aarhus University. This research has been conducted using the Danish National Biobank resource, supported by the Novo Nordisk Foundation. VA was supported by grants from the Australian Research Council (DP170102402), John T. Reid Charitable Trusts and the Clem Jones Centre for Ageing DementiaResearch. SEJ is a University of Queensland International Scholar. NRW was supported by NHMRC grants (APP1078901, APP1087889, APP1113400). These funding agencies were not involved in any aspect of the study.

Publisher Copyright:
© 2018, The Author(s).

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Eyles, D. W., Trzaskowski, M., Vinkhuyzen, A. A. E., Mattheisen, M., Meier, S., Gooch, H., Anggono, V., Cui, X., Tan, M. C., Burne, T. H. J., Jang, S. E., Kvaskoff, D., Hougaard, D. M., Nørgaard-Pedersen, B., Cohen, A., Agerbo, E., Pedersen, C. B., Børglum, A. D., Mors, O., ... McGrath, J. J. (2018). The association between neonatal vitamin D status and risk of schizophrenia. Scientific Reports, 8(1), Artículo 17692. https://doi.org/10.1038/s41598-018-35418-z

Eyles, DW, Trzaskowski, M, Vinkhuyzen, AAE, Mattheisen, M, Meier, S, Gooch, H, Anggono, V, Cui, X, Tan, MC, Burne, THJ, Jang, SE, Kvaskoff, D, Hougaard, DM, Nørgaard-Pedersen, B, Cohen, A, Agerbo, E, Pedersen, CB, Børglum, AD, Mors, O, Sah, P, Wray, NR, Mortensen, PB & McGrath, JJ 2018, 'The association between neonatal vitamin D status and risk of schizophrenia', Scientific Reports, vol. 8, n.º 1, 17692. https://doi.org/10.1038/s41598-018-35418-z

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abstract = "Clues from the epidemiology of schizophrenia, such as the increased risk in those born in winter/spring, have led to the hypothesis that prenatal vitamin D deficiency may increase the risk of later schizophrenia. We wish to explore this hypothesis in a large Danish case-control study (n = 2602). The concentration of 25 hydroxyvitamin D (25OHD) was assessed from neonatal dried blood samples. Incidence rate ratios (IRR) were calculated when examined for quintiles of 25OHD concentration. In addition, we examined statistical models that combined 25OHD concentration and the schizophrenia polygenic risk score (PRS) in a sample that combined the new sample with a previous study (total n = 3464; samples assayed and genotyped between 2008-2013). Compared to the reference (fourth) quintile, those in the lowest quintile (<20.4 nmol/L) had a significantly increased risk of schizophrenia (IRR = 1.44, 95%CI: 1.12–1.85). None of the other quintile comparisons were significantly different. There was no significant interaction between 25OHD and the PRS. Neonatal vitamin D deficiency was associated with an increased risk for schizophrenia in later life. These findings could have important public health implications related to the primary prevention of schizophrenia.",

author = "Eyles, {Darryl W.} and Maciej Trzaskowski and Vinkhuyzen, {Anna A.E.} and Manuel Mattheisen and Sandra Meier and Helen Gooch and Victor Anggono and Xiaoying Cui and Tan, {Men Chee} and Burne, {Thomas H.J.} and Jang, {Se Eun} and David Kvaskoff and Hougaard, {David M.} and Bent N{\o}rgaard-Pedersen and Arieh Cohen and Esben Agerbo and Pedersen, {Carsten B.} and B{\o}rglum, {Anders D.} and Ole Mors and Pankaj Sah and Wray, {Naomi R.} and Mortensen, {Preben B.} and McGrath, {John J.}",

note = "Funding Information: We thank Peter Josh, Henry Simila and Pauline Ko for assistance with vitamin D assays, and Gavin Bird and Karin Bird for general support related to this field of research. This project was supported by NHMRC Project grants (APP 1007677, APP 1099709) and a John Cade Fellowship (APP1056929). JM was supported by a Niels Bohr Professorship from the Danish National Research Foundation. This study was supported by the Lundbeck Foundation (grant no R102-A9118 and R155-2014-1724), Denmark; the Stanley Medical Research Institute; an Advanced Grant from the European Research Council (project no: 294838); the Stanley Center for Psychiatric Research at Broad Institute and Centre for Integrated Register-based Research at Aarhus University. This research has been conducted using the Danish National Biobank resource, supported by the Novo Nordisk Foundation. VA was supported by grants from the Australian Research Council (DP170102402), John T. Reid Charitable Trusts and the Clem Jones Centre for Ageing DementiaResearch. SEJ is a University of Queensland International Scholar. NRW was supported by NHMRC grants (APP1078901, APP1087889, APP1113400). These funding agencies were not involved in any aspect of the study. Publisher Copyright: {\textcopyright} 2018, The Author(s).",

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The association between neonatal vitamin D status and risk of schizophrenia

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