Association of GRIN1 and GRIN2A-D With schizophrenia and genetic interaction with maternal herpes simplex virus-2 infection affecting disease risk

Ditte Demontis; Mette Nyegaard; Henriette Nørmølle Buttenschøn; Anne Hedemand; Carsten B Pedersen; Jakob Grove; Tracey Flint Zacharov; Merete Nordentoft; Thomas Werge; David M Hougaard; Karina M Sørensen; Robert H Yolken; Ole Mors; Anders Børglum; Preben Bo Mortensen

doi:10.1002/ajmg.b.31234

Association of GRIN1 and GRIN2A-D With schizophrenia and genetic interaction with maternal herpes simplex virus-2 infection affecting disease risk

Ditte Demontis, Mette Nyegaard, Henriette Nørmølle Buttenschøn, Anne Hedemand, Carsten B Pedersen, Jakob Grove, Tracey Flint Zacharov, Merete Nordentoft, Thomas Werge, David M Hougaard, Karina M Sørensen, Robert H Yolken, Ole Mors, Anders Børglum, Preben Bo Mortensen

38 Citations (Scopus)

Abstract

N-methyl-D-aspartate (NMDA) receptors are very important for proper brain development and several lines of evidence support that hypofunction of the NMDA receptors are involved in the pathophysiology of schizophrenia. Gene variation and gene-environmental interactions involving the genes encoding the NMDA receptors are therefore likely to influence the risk of schizophrenia. The aim of this study was to determine (1) whether SNP variation in the genes (GRIN1, GRIN2A, GRIN2B, GRIN2C, and GRIN2D) encoding the NMDA receptor were associated with schizophrenia; (2) whether GRIN gene variation in the offspring interacted with maternal herpes simplex virus-2 (HSV-2) seropositivity during pregnancy influencing the risk of schizophrenia later in life. Individuals from three independently collected Danish case control samples were genotyped for 81 tagSNPs (in total 984 individuals diagnosed with schizophrenia and 1,500 control persons) and antibodies against maternal HSV-2 infection were measured in one of the samples (365 cases and 365 controls). Nine SNPs out of 30 in GRIN2B were significantly associated with schizophrenia. One SNP remained significant after Bonferroni correction (rs1806194, P_nominal=0.0008). Significant interaction between maternal HSV-2 seropositivity and GRIN2B genetic variation in the offspring were observed for seven SNPs and two remained significant after Bonferroni correction (rs1805539, P_nominal=0.0001 and rs1806205, P_nominal=0.0008). The significant associations and interactions were located at the 3' region of GRIN2B suggesting that genetic variation in this part of the gene may be involved in the pathophysiology of schizophrenia.

Original language	English
Journal	American Journal of Medical Genetics. Part B: Neuropsychiatric Genetics
Volume	156
Issue number	8
Pages (from-to)	913-22
Number of pages	10
ISSN	1552-4841
DOIs	https://doi.org/10.1002/ajmg.b.31234
Publication status	Published - 1 Dec 2011

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Demontis, D., Nyegaard, M., Buttenschøn, H. N., Hedemand, A., Pedersen, C. B., Grove, J., Zacharov, T. F., Nordentoft, M., Werge, T., Hougaard, D. M., Sørensen, K. M., Yolken, R. H., Mors, O., Børglum, A., & Mortensen, P. B. (2011). Association of GRIN1 and GRIN2A-D With schizophrenia and genetic interaction with maternal herpes simplex virus-2 infection affecting disease risk. American Journal of Medical Genetics. Part B: Neuropsychiatric Genetics, 156(8), 913-22. https://doi.org/10.1002/ajmg.b.31234

Association of GRIN1 and GRIN2A-D With schizophrenia and genetic interaction with maternal herpes simplex virus-2 infection affecting disease risk. / Demontis, Ditte; Nyegaard, Mette; Buttenschøn, Henriette Nørmølle et al.

In: American Journal of Medical Genetics. Part B: Neuropsychiatric Genetics, Vol. 156, No. 8, 01.12.2011, p. 913-22.

Research output: Contribution to journal › Journal article › Research › peer-review

Demontis, D, Nyegaard, M, Buttenschøn, HN, Hedemand, A, Pedersen, CB, Grove, J, Zacharov, TF, Nordentoft, M , Werge, T, Hougaard, DM, Sørensen, KM, Yolken, RH, Mors, O, Børglum, A & Mortensen, PB 2011, 'Association of GRIN1 and GRIN2A-D With schizophrenia and genetic interaction with maternal herpes simplex virus-2 infection affecting disease risk', American Journal of Medical Genetics. Part B: Neuropsychiatric Genetics, vol. 156, no. 8, pp. 913-22. https://doi.org/10.1002/ajmg.b.31234

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title = "Association of GRIN1 and GRIN2A-D With schizophrenia and genetic interaction with maternal herpes simplex virus-2 infection affecting disease risk",

abstract = "N-methyl-D-aspartate (NMDA) receptors are very important for proper brain development and several lines of evidence support that hypofunction of the NMDA receptors are involved in the pathophysiology of schizophrenia. Gene variation and gene-environmental interactions involving the genes encoding the NMDA receptors are therefore likely to influence the risk of schizophrenia. The aim of this study was to determine (1) whether SNP variation in the genes (GRIN1, GRIN2A, GRIN2B, GRIN2C, and GRIN2D) encoding the NMDA receptor were associated with schizophrenia; (2) whether GRIN gene variation in the offspring interacted with maternal herpes simplex virus-2 (HSV-2) seropositivity during pregnancy influencing the risk of schizophrenia later in life. Individuals from three independently collected Danish case control samples were genotyped for 81 tagSNPs (in total 984 individuals diagnosed with schizophrenia and 1,500 control persons) and antibodies against maternal HSV-2 infection were measured in one of the samples (365 cases and 365 controls). Nine SNPs out of 30 in GRIN2B were significantly associated with schizophrenia. One SNP remained significant after Bonferroni correction (rs1806194, Pnominal=0.0008). Significant interaction between maternal HSV-2 seropositivity and GRIN2B genetic variation in the offspring were observed for seven SNPs and two remained significant after Bonferroni correction (rs1805539, Pnominal=0.0001 and rs1806205, Pnominal=0.0008). The significant associations and interactions were located at the 3' region of GRIN2B suggesting that genetic variation in this part of the gene may be involved in the pathophysiology of schizophrenia.",

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AU - Demontis, Ditte

AU - Nyegaard, Mette

AU - Buttenschøn, Henriette Nørmølle

AU - Hedemand, Anne

AU - Pedersen, Carsten B

AU - Grove, Jakob

AU - Zacharov, Tracey Flint

AU - Nordentoft, Merete

AU - Werge, Thomas

AU - Hougaard, David M

AU - Sørensen, Karina M

AU - Yolken, Robert H

AU - Mors, Ole

AU - Børglum, Anders

AU - Mortensen, Preben Bo

PY - 2011/12/1

Y1 - 2011/12/1

N2 - N-methyl-D-aspartate (NMDA) receptors are very important for proper brain development and several lines of evidence support that hypofunction of the NMDA receptors are involved in the pathophysiology of schizophrenia. Gene variation and gene-environmental interactions involving the genes encoding the NMDA receptors are therefore likely to influence the risk of schizophrenia. The aim of this study was to determine (1) whether SNP variation in the genes (GRIN1, GRIN2A, GRIN2B, GRIN2C, and GRIN2D) encoding the NMDA receptor were associated with schizophrenia; (2) whether GRIN gene variation in the offspring interacted with maternal herpes simplex virus-2 (HSV-2) seropositivity during pregnancy influencing the risk of schizophrenia later in life. Individuals from three independently collected Danish case control samples were genotyped for 81 tagSNPs (in total 984 individuals diagnosed with schizophrenia and 1,500 control persons) and antibodies against maternal HSV-2 infection were measured in one of the samples (365 cases and 365 controls). Nine SNPs out of 30 in GRIN2B were significantly associated with schizophrenia. One SNP remained significant after Bonferroni correction (rs1806194, Pnominal=0.0008). Significant interaction between maternal HSV-2 seropositivity and GRIN2B genetic variation in the offspring were observed for seven SNPs and two remained significant after Bonferroni correction (rs1805539, Pnominal=0.0001 and rs1806205, Pnominal=0.0008). The significant associations and interactions were located at the 3' region of GRIN2B suggesting that genetic variation in this part of the gene may be involved in the pathophysiology of schizophrenia.

AB - N-methyl-D-aspartate (NMDA) receptors are very important for proper brain development and several lines of evidence support that hypofunction of the NMDA receptors are involved in the pathophysiology of schizophrenia. Gene variation and gene-environmental interactions involving the genes encoding the NMDA receptors are therefore likely to influence the risk of schizophrenia. The aim of this study was to determine (1) whether SNP variation in the genes (GRIN1, GRIN2A, GRIN2B, GRIN2C, and GRIN2D) encoding the NMDA receptor were associated with schizophrenia; (2) whether GRIN gene variation in the offspring interacted with maternal herpes simplex virus-2 (HSV-2) seropositivity during pregnancy influencing the risk of schizophrenia later in life. Individuals from three independently collected Danish case control samples were genotyped for 81 tagSNPs (in total 984 individuals diagnosed with schizophrenia and 1,500 control persons) and antibodies against maternal HSV-2 infection were measured in one of the samples (365 cases and 365 controls). Nine SNPs out of 30 in GRIN2B were significantly associated with schizophrenia. One SNP remained significant after Bonferroni correction (rs1806194, Pnominal=0.0008). Significant interaction between maternal HSV-2 seropositivity and GRIN2B genetic variation in the offspring were observed for seven SNPs and two remained significant after Bonferroni correction (rs1805539, Pnominal=0.0001 and rs1806205, Pnominal=0.0008). The significant associations and interactions were located at the 3' region of GRIN2B suggesting that genetic variation in this part of the gene may be involved in the pathophysiology of schizophrenia.

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DO - 10.1002/ajmg.b.31234

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SN - 1552-4841

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JO - American Journal of Medical Genetics, Part B: Neuropsychiatric Genetics

JF - American Journal of Medical Genetics, Part B: Neuropsychiatric Genetics

IS - 8

ER -

Association of GRIN1 and GRIN2A-D With schizophrenia and genetic interaction with maternal herpes simplex virus-2 infection affecting disease risk

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