Genome-wide association study of NMDA receptor coagonists in human cerebrospinal fluid and plasma

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Genome-wide association study of NMDA receptor coagonists in human cerebrospinal fluid and plasma. / Luykx, J. J.; Bakker, S. C.; Visser, W. F.; Verhoeven-Duif, N.; Buizer-Voskamp, J. E.; Den Heijer, J. M.; Boks, M. P.M.; Sul, J. H.; Eskin, E.; Ori, A. P.; Cantor, R. M.; Vorstman, J.; Strengman, E.; Deyoung, J.; Kappen, T. H.; Pariama, E.; Van Dongen, E. P.A.; Borgdorff, P.; Bruins, P.; De Koning, T. J.; Kahn, R. S.; Ophoff, R. A.

In: Molecular Psychiatry, Vol. 20, No. 12, 01.12.2015, p. 1557-1564.

Research output: Contribution to journalArticle

Harvard

Luykx, JJ, Bakker, SC, Visser, WF, Verhoeven-Duif, N, Buizer-Voskamp, JE, Den Heijer, JM, Boks, MPM, Sul, JH, Eskin, E, Ori, AP, Cantor, RM, Vorstman, J, Strengman, E, Deyoung, J, Kappen, TH, Pariama, E, Van Dongen, EPA, Borgdorff, P, Bruins, P, De Koning, TJ, Kahn, RS & Ophoff, RA 2015, 'Genome-wide association study of NMDA receptor coagonists in human cerebrospinal fluid and plasma', Molecular Psychiatry, vol. 20, no. 12, pp. 1557-1564. https://doi.org/10.1038/mp.2014.190

APA

Luykx, J. J., Bakker, S. C., Visser, W. F., Verhoeven-Duif, N., Buizer-Voskamp, J. E., Den Heijer, J. M., Boks, M. P. M., Sul, J. H., Eskin, E., Ori, A. P., Cantor, R. M., Vorstman, J., Strengman, E., Deyoung, J., Kappen, T. H., Pariama, E., Van Dongen, E. P. A., Borgdorff, P., Bruins, P., ... Ophoff, R. A. (2015). Genome-wide association study of NMDA receptor coagonists in human cerebrospinal fluid and plasma. Molecular Psychiatry, 20(12), 1557-1564. https://doi.org/10.1038/mp.2014.190

CBE

Luykx JJ, Bakker SC, Visser WF, Verhoeven-Duif N, Buizer-Voskamp JE, Den Heijer JM, Boks MPM, Sul JH, Eskin E, Ori AP, Cantor RM, Vorstman J, Strengman E, Deyoung J, Kappen TH, Pariama E, Van Dongen EPA, Borgdorff P, Bruins P, De Koning TJ, Kahn RS, Ophoff RA. 2015. Genome-wide association study of NMDA receptor coagonists in human cerebrospinal fluid and plasma. Molecular Psychiatry. 20(12):1557-1564. https://doi.org/10.1038/mp.2014.190

MLA

Vancouver

Luykx JJ, Bakker SC, Visser WF, Verhoeven-Duif N, Buizer-Voskamp JE, Den Heijer JM et al. Genome-wide association study of NMDA receptor coagonists in human cerebrospinal fluid and plasma. Molecular Psychiatry. 2015 Dec 1;20(12):1557-1564. https://doi.org/10.1038/mp.2014.190

Author

Luykx, J. J. ; Bakker, S. C. ; Visser, W. F. ; Verhoeven-Duif, N. ; Buizer-Voskamp, J. E. ; Den Heijer, J. M. ; Boks, M. P.M. ; Sul, J. H. ; Eskin, E. ; Ori, A. P. ; Cantor, R. M. ; Vorstman, J. ; Strengman, E. ; Deyoung, J. ; Kappen, T. H. ; Pariama, E. ; Van Dongen, E. P.A. ; Borgdorff, P. ; Bruins, P. ; De Koning, T. J. ; Kahn, R. S. ; Ophoff, R. A. / Genome-wide association study of NMDA receptor coagonists in human cerebrospinal fluid and plasma. In: Molecular Psychiatry. 2015 ; Vol. 20, No. 12. pp. 1557-1564.

RIS

TY - JOUR

T1 - Genome-wide association study of NMDA receptor coagonists in human cerebrospinal fluid and plasma

AU - Luykx, J. J.

AU - Bakker, S. C.

AU - Visser, W. F.

AU - Verhoeven-Duif, N.

AU - Buizer-Voskamp, J. E.

AU - Den Heijer, J. M.

AU - Boks, M. P.M.

AU - Sul, J. H.

AU - Eskin, E.

AU - Ori, A. P.

AU - Cantor, R. M.

AU - Vorstman, J.

AU - Strengman, E.

AU - Deyoung, J.

AU - Kappen, T. H.

AU - Pariama, E.

AU - Van Dongen, E. P.A.

AU - Borgdorff, P.

AU - Bruins, P.

AU - De Koning, T. J.

AU - Kahn, R. S.

AU - Ophoff, R. A.

PY - 2015/12/1

Y1 - 2015/12/1

N2 - The N-methyl-d-aspartate receptor (NMDAR) coagonists glycine, d-serine and l-proline play crucial roles in NMDAR-dependent neurotransmission and are associated with a range of neuropsychiatric disorders. We conducted the first genome-wide association study of concentrations of these coagonists and their enantiomers in plasma and cerebrospinal fluid (CSF) of human subjects from the general population (N=414). Genetic variants at chromosome 22q11.2, located in and near PRODH (proline dehydrogenase), were associated with l-proline in plasma (β=0.29; P=6.38 × 10 -10). The missense variant rs17279437 in the proline transporter SLC6A20 was associated with l-proline in CSF (β=0.28; P=9.68 × 10 -9). Suggestive evidence of association was found for the d-serine plasma-CSF ratio at the d-amino-acid oxidase (DAO) gene (β=-0.28; P=9.08 × 10 -8), whereas a variant in SRR (that encodes serine racemase and is associated with schizophrenia) constituted the most strongly associated locus for the l-serine to d-serine ratio in CSF. All these genes are highly expressed in rodent meninges and choroid plexus, anatomical regions relevant to CSF physiology. The enzymes and transporters they encode may be targeted to further construe the nature of NMDAR coagonist involvement in NMDAR gating. Furthermore, the highlighted genetic variants may be followed up in clinical populations, for example, schizophrenia and 22q11 deletion syndrome. Overall, this targeted metabolomics approach furthers the understanding of NMDAR coagonist concentration variability and sets the stage for non-targeted CSF metabolomics projects.

AB - The N-methyl-d-aspartate receptor (NMDAR) coagonists glycine, d-serine and l-proline play crucial roles in NMDAR-dependent neurotransmission and are associated with a range of neuropsychiatric disorders. We conducted the first genome-wide association study of concentrations of these coagonists and their enantiomers in plasma and cerebrospinal fluid (CSF) of human subjects from the general population (N=414). Genetic variants at chromosome 22q11.2, located in and near PRODH (proline dehydrogenase), were associated with l-proline in plasma (β=0.29; P=6.38 × 10 -10). The missense variant rs17279437 in the proline transporter SLC6A20 was associated with l-proline in CSF (β=0.28; P=9.68 × 10 -9). Suggestive evidence of association was found for the d-serine plasma-CSF ratio at the d-amino-acid oxidase (DAO) gene (β=-0.28; P=9.08 × 10 -8), whereas a variant in SRR (that encodes serine racemase and is associated with schizophrenia) constituted the most strongly associated locus for the l-serine to d-serine ratio in CSF. All these genes are highly expressed in rodent meninges and choroid plexus, anatomical regions relevant to CSF physiology. The enzymes and transporters they encode may be targeted to further construe the nature of NMDAR coagonist involvement in NMDAR gating. Furthermore, the highlighted genetic variants may be followed up in clinical populations, for example, schizophrenia and 22q11 deletion syndrome. Overall, this targeted metabolomics approach furthers the understanding of NMDAR coagonist concentration variability and sets the stage for non-targeted CSF metabolomics projects.

UR - http://www.scopus.com/inward/record.url?scp=84947617141&partnerID=8YFLogxK

U2 - 10.1038/mp.2014.190

DO - 10.1038/mp.2014.190

M3 - Article

C2 - 25666758

AN - SCOPUS:84947617141

VL - 20

SP - 1557

EP - 1564

JO - Molecular Psychiatry

JF - Molecular Psychiatry

SN - 1359-4184

IS - 12

ER -