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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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; Hedemand, Anne; Pedersen, Carsten B; Grove, Jakob; Zacharov, Tracey Flint; Nordentoft, Merete; Werge, Thomas; Hougaard, David M; Sørensen, Karina M; Yolken, Robert H; Mors, Ole; Børglum, Anders; Mortensen, Preben Bo.
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
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TY - JOUR
T1 - Association of GRIN1 and GRIN2A-D With schizophrenia and genetic interaction with maternal herpes simplex virus-2 infection affecting disease risk
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
N1 - Copyright © 2011 Wiley Periodicals, Inc.
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, 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. © 2011 Wiley Periodicals, Inc.
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, 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. © 2011 Wiley Periodicals, Inc.
U2 - 10.1002/ajmg.b.31234
DO - 10.1002/ajmg.b.31234
M3 - Journal article
C2 - 21919190
VL - 156
SP - 913
EP - 922
JO - American Journal of Medical Genetics. Part B: Neuropsychiatric Genetics
JF - American Journal of Medical Genetics. Part B: Neuropsychiatric Genetics
SN - 1552-4841
IS - 8
ER -
ID: 40183640