Polymorphisms in SREBF1 and SREBF2, two antipsychotic-activated transcription factors controlling cellular lipogenesis, are associated with schizophrenia in German and Scandinavian samples

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Standard

Polymorphisms in SREBF1 and SREBF2, two antipsychotic-activated transcription factors controlling cellular lipogenesis, are associated with schizophrenia in German and Scandinavian samples. / Le Hellard, S; Mühleisen, T W; Djurovic, S; Fernø, J; Ouriaghi, Z; Mattheisen, M; Vasilescu, C; Raeder, M B; Hansen, Thomas Folkmann; Strohmaier, J; Georgi, A; Brockschmidt, F F; Melle, I; Nenadic, I; Sauer, H; Rietschel, M; Nöthen, M M; Werge, T; Andreassen, O A; Cichon, S; Steen, V M.

In: Molecular Psychiatry, Vol. 15, No. 5, 01.05.2010, p. 463-72.

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

Harvard

Le Hellard, S, Mühleisen, TW, Djurovic, S, Fernø, J, Ouriaghi, Z, Mattheisen, M, Vasilescu, C, Raeder, MB, Hansen, TF, Strohmaier, J, Georgi, A, Brockschmidt, FF, Melle, I, Nenadic, I, Sauer, H, Rietschel, M, Nöthen, MM, Werge, T, Andreassen, OA, Cichon, S & Steen, VM 2010, 'Polymorphisms in SREBF1 and SREBF2, two antipsychotic-activated transcription factors controlling cellular lipogenesis, are associated with schizophrenia in German and Scandinavian samples', Molecular Psychiatry, vol. 15, no. 5, pp. 463-72. https://doi.org/10.1038/mp.2008.110

APA

Le Hellard, S., Mühleisen, T. W., Djurovic, S., Fernø, J., Ouriaghi, Z., Mattheisen, M., Vasilescu, C., Raeder, M. B., Hansen, T. F., Strohmaier, J., Georgi, A., Brockschmidt, F. F., Melle, I., Nenadic, I., Sauer, H., Rietschel, M., Nöthen, M. M., Werge, T., Andreassen, O. A., ... Steen, V. M. (2010). Polymorphisms in SREBF1 and SREBF2, two antipsychotic-activated transcription factors controlling cellular lipogenesis, are associated with schizophrenia in German and Scandinavian samples. Molecular Psychiatry, 15(5), 463-72. https://doi.org/10.1038/mp.2008.110

Vancouver

Le Hellard S, Mühleisen TW, Djurovic S, Fernø J, Ouriaghi Z, Mattheisen M et al. Polymorphisms in SREBF1 and SREBF2, two antipsychotic-activated transcription factors controlling cellular lipogenesis, are associated with schizophrenia in German and Scandinavian samples. Molecular Psychiatry. 2010 May 1;15(5):463-72. https://doi.org/10.1038/mp.2008.110

Author

Le Hellard, S ; Mühleisen, T W ; Djurovic, S ; Fernø, J ; Ouriaghi, Z ; Mattheisen, M ; Vasilescu, C ; Raeder, M B ; Hansen, Thomas Folkmann ; Strohmaier, J ; Georgi, A ; Brockschmidt, F F ; Melle, I ; Nenadic, I ; Sauer, H ; Rietschel, M ; Nöthen, M M ; Werge, T ; Andreassen, O A ; Cichon, S ; Steen, V M. / Polymorphisms in SREBF1 and SREBF2, two antipsychotic-activated transcription factors controlling cellular lipogenesis, are associated with schizophrenia in German and Scandinavian samples. In: Molecular Psychiatry. 2010 ; Vol. 15, No. 5. pp. 463-72.

Bibtex

@article{754361c35139435ea104907decbdb095,
title = "Polymorphisms in SREBF1 and SREBF2, two antipsychotic-activated transcription factors controlling cellular lipogenesis, are associated with schizophrenia in German and Scandinavian samples",
abstract = "Several studies have reported structural brain abnormalities, decreased myelination and oligodendrocyte dysfunction in schizophrenia. In the central nervous system, glia-derived de novo synthesized cholesterol is essential for both myelination and synaptogenesis. Previously, we demonstrated in glial cell lines that antipsychotic drugs induce the expression of genes involved in cholesterol and fatty acids biosynthesis through activation of the sterol regulatory element binding protein (SREBP) transcription factors, encoded by the sterol regulatory element binding transcription factor 1 (SREBF1) and sterol regulatory element binding transcription factor 2 (SREBF2) genes. Considering the importance of these factors in the lipid biosynthesis and their possible involvement in antipsychotic drug effects, we hypothesized that genetic variants of SREBF1 and/or SREBF2 could affect schizophrenia susceptibility. We therefore conducted a HapMap-based association study in a large German sample, and identified association between schizophrenia and five markers in SREBF1 and five markers in SREBF2. Follow-up studies in two independent samples of Danish and Norwegian origin (part of the Scandinavian collaboration of psychiatric etiology study, SCOPE) replicated the association for the five SREBF1 markers and for two markers in SREBF2. A combined analysis of all samples resulted in highly significant genotypic P-values of 9 x 10(-4) for SREBF1 (rs11868035, odd ration (OR)=1.26, 95% confidence interval (CI) (1.09-1.45)) and 4 x 10(-5) for SREBF2 (rs1057217, OR=1.39, 95% CI (1.19-1.63)). This finding strengthens the hypothesis that SREBP-controlled cholesterol biosynthesis is involved in the etiology of schizophrenia.",
author = "{Le Hellard}, S and M{\"u}hleisen, {T W} and S Djurovic and J Fern{\o} and Z Ouriaghi and M Mattheisen and C Vasilescu and Raeder, {M B} and Hansen, {Thomas Folkmann} and J Strohmaier and A Georgi and Brockschmidt, {F F} and I Melle and I Nenadic and H Sauer and M Rietschel and N{\"o}then, {M M} and T Werge and Andreassen, {O A} and S Cichon and Steen, {V M}",
year = "2010",
month = may,
day = "1",
doi = "http://dx.doi.org/10.1038/mp.2008.110",
language = "English",
volume = "15",
pages = "463--72",
journal = "Molecular Psychiatry",
issn = "1359-4184",
publisher = "nature publishing group",
number = "5",

}

RIS

TY - JOUR

T1 - Polymorphisms in SREBF1 and SREBF2, two antipsychotic-activated transcription factors controlling cellular lipogenesis, are associated with schizophrenia in German and Scandinavian samples

AU - Le Hellard, S

AU - Mühleisen, T W

AU - Djurovic, S

AU - Fernø, J

AU - Ouriaghi, Z

AU - Mattheisen, M

AU - Vasilescu, C

AU - Raeder, M B

AU - Hansen, Thomas Folkmann

AU - Strohmaier, J

AU - Georgi, A

AU - Brockschmidt, F F

AU - Melle, I

AU - Nenadic, I

AU - Sauer, H

AU - Rietschel, M

AU - Nöthen, M M

AU - Werge, T

AU - Andreassen, O A

AU - Cichon, S

AU - Steen, V M

PY - 2010/5/1

Y1 - 2010/5/1

N2 - Several studies have reported structural brain abnormalities, decreased myelination and oligodendrocyte dysfunction in schizophrenia. In the central nervous system, glia-derived de novo synthesized cholesterol is essential for both myelination and synaptogenesis. Previously, we demonstrated in glial cell lines that antipsychotic drugs induce the expression of genes involved in cholesterol and fatty acids biosynthesis through activation of the sterol regulatory element binding protein (SREBP) transcription factors, encoded by the sterol regulatory element binding transcription factor 1 (SREBF1) and sterol regulatory element binding transcription factor 2 (SREBF2) genes. Considering the importance of these factors in the lipid biosynthesis and their possible involvement in antipsychotic drug effects, we hypothesized that genetic variants of SREBF1 and/or SREBF2 could affect schizophrenia susceptibility. We therefore conducted a HapMap-based association study in a large German sample, and identified association between schizophrenia and five markers in SREBF1 and five markers in SREBF2. Follow-up studies in two independent samples of Danish and Norwegian origin (part of the Scandinavian collaboration of psychiatric etiology study, SCOPE) replicated the association for the five SREBF1 markers and for two markers in SREBF2. A combined analysis of all samples resulted in highly significant genotypic P-values of 9 x 10(-4) for SREBF1 (rs11868035, odd ration (OR)=1.26, 95% confidence interval (CI) (1.09-1.45)) and 4 x 10(-5) for SREBF2 (rs1057217, OR=1.39, 95% CI (1.19-1.63)). This finding strengthens the hypothesis that SREBP-controlled cholesterol biosynthesis is involved in the etiology of schizophrenia.

AB - Several studies have reported structural brain abnormalities, decreased myelination and oligodendrocyte dysfunction in schizophrenia. In the central nervous system, glia-derived de novo synthesized cholesterol is essential for both myelination and synaptogenesis. Previously, we demonstrated in glial cell lines that antipsychotic drugs induce the expression of genes involved in cholesterol and fatty acids biosynthesis through activation of the sterol regulatory element binding protein (SREBP) transcription factors, encoded by the sterol regulatory element binding transcription factor 1 (SREBF1) and sterol regulatory element binding transcription factor 2 (SREBF2) genes. Considering the importance of these factors in the lipid biosynthesis and their possible involvement in antipsychotic drug effects, we hypothesized that genetic variants of SREBF1 and/or SREBF2 could affect schizophrenia susceptibility. We therefore conducted a HapMap-based association study in a large German sample, and identified association between schizophrenia and five markers in SREBF1 and five markers in SREBF2. Follow-up studies in two independent samples of Danish and Norwegian origin (part of the Scandinavian collaboration of psychiatric etiology study, SCOPE) replicated the association for the five SREBF1 markers and for two markers in SREBF2. A combined analysis of all samples resulted in highly significant genotypic P-values of 9 x 10(-4) for SREBF1 (rs11868035, odd ration (OR)=1.26, 95% confidence interval (CI) (1.09-1.45)) and 4 x 10(-5) for SREBF2 (rs1057217, OR=1.39, 95% CI (1.19-1.63)). This finding strengthens the hypothesis that SREBP-controlled cholesterol biosynthesis is involved in the etiology of schizophrenia.

U2 - http://dx.doi.org/10.1038/mp.2008.110

DO - http://dx.doi.org/10.1038/mp.2008.110

M3 - Journal article

VL - 15

SP - 463

EP - 472

JO - Molecular Psychiatry

JF - Molecular Psychiatry

SN - 1359-4184

IS - 5

ER -

ID: 34053603