Association study of PDE4B gene variants in Scandinavian schizophrenia and bipolar disorder multicenter case-control samples

Anna K Kähler; Mona K Otnæss; Katrine V Wirgenes; Thomas Hansen; Erik G Jönsson; Ingrid Agartz; Håkan Hall; Thomas Werge; Gunnar Morken; Ole Mors; Erling Mellerup; Henrik Dam; Pernille Koefoed; Ingrid Melle; Vidar M Steen; Ole A Andreassen; Srdjan Djurovic; Anna K Kähler; Mona K Otnaess; Katrine V Wirgenes; Thomas Hansen; Erik G Jönsson; Ingrid Agartz; Håkan Hall; Thomas Werge; Gunnar Morken; Ole Mors; Erling Mellerup; Henrik Dam; Pernille Koefod; Ingrid Melle; Vidar M Steen; Ole A Andreassen; Srdjan Djurovic

doi:10.1002/ajmg.b.30958

Association study of PDE4B gene variants in Scandinavian schizophrenia and bipolar disorder multicenter case-control samples

Anna K Kähler, Mona K Otnæss, Katrine V Wirgenes, Thomas Hansen, Erik G Jönsson, Ingrid Agartz, Håkan Hall, Thomas Werge, Gunnar Morken, Ole Mors, Erling Mellerup, Henrik Dam, Pernille Koefoed, Ingrid Melle, Vidar M Steen, Ole A Andreassen, Srdjan Djurovic, Anna K Kähler, Mona K Otnaess, Katrine V WirgenesThomas Hansen, Erik G Jönsson, Ingrid Agartz, Håkan Hall, Thomas Werge, Gunnar Morken, Ole Mors, Erling Mellerup, Henrik Dam, Pernille Koefod, Ingrid Melle, Vidar M Steen, Ole A Andreassen, Srdjan Djurovic

29 Citations (Scopus)

Abstract

The phosphodiesterase 4B (PDE4B), which is involved in cognitive function in animal models, is a candidate susceptibility gene for schizophrenia (SZ) and bipolar disorder (BP). Variations in PDE4B have previously been associated with SZ, with a suggested gender-specific effect.Wehave genotyped and analyzed 40 and 72 tagging single nucleotide polymorphisms (tagSNPs) in SZ and BP multicenter samples, respectively, from the Scandinavian Collaboration on Psychiatric Etiology (SCOPE), involving 837 SZ cases and 1,473 controls plus 594 BP cases and 1,421 partly overlapping controls. Six and 16 tagSNPs were nominally associated (0.0005≤P≤0.05) with SZ and BP, respectively, in the combined samples or in gender-specific subgroups. None of these findings remained significant after correction for multiple testing. However, a number of tagSNPs found to be nominally associated with SZ and BP were located in a high LD region spanning the splice site of PDE4B3, an isoform with altered brain expression in BP patients. Four tagSNPs were associated with SZ in women, but none in men, in agreement with the previously reported gender-specific effect. Proxies of two nominally associated SNPs in the SZ sample were also associated with BP, but the genotypic effect (i.e., homozygosity for the minor allele), pointed in opposite directions. Finally, four SNPs were found to be associated with Positive And Negative Syndrome Scale (PANSS) positive symptom scores in a subgroup of SZ patients (n=153) or SZ female patients (n=70). Further studies are needed to evaluate the implicated PDE4B region of interest, for potential involvement in SZ and BP susceptibility.

Original language	English
Journal	American Journal of Medical Genetics. Part B: Neuropsychiatric Genetics
Volume	153B
Issue number	1
Pages (from-to)	86-96
Number of pages	11
ISSN	1552-4841
DOIs	https://doi.org/10.1002/ajmg.b.30958
Publication status	Published - Jan 2010

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Kähler, A. K., Otnæss, M. K., Wirgenes, K. V., Hansen, T., Jönsson, E. G., Agartz, I., Hall, H., Werge, T., Morken, G., Mors, O., Mellerup, E., Dam, H., Koefoed, P., Melle, I., Steen, V. M., Andreassen, O. A., Djurovic, S., Kähler, A. K., Otnaess, M. K., ... Djurovic, S. (2010). Association study of PDE4B gene variants in Scandinavian schizophrenia and bipolar disorder multicenter case-control samples. American Journal of Medical Genetics. Part B: Neuropsychiatric Genetics, 153B(1), 86-96. https://doi.org/10.1002/ajmg.b.30958

Association study of PDE4B gene variants in Scandinavian schizophrenia and bipolar disorder multicenter case-control samples. / Kähler, Anna K; Otnæss, Mona K; Wirgenes, Katrine V et al.

In: American Journal of Medical Genetics. Part B: Neuropsychiatric Genetics, Vol. 153B, No. 1, 01.2010, p. 86-96.

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

Kähler, AK, Otnæss, MK, Wirgenes, KV, Hansen, T, Jönsson, EG, Agartz, I, Hall, H, Werge, T, Morken, G, Mors, O, Mellerup, E, Dam, H, Koefoed, P, Melle, I, Steen, VM, Andreassen, OA, Djurovic, S, Kähler, AK, Otnaess, MK, Wirgenes, KV, Hansen, T, Jönsson, EG, Agartz, I, Hall, H, Werge, T, Morken, G, Mors, O, Mellerup, E, Dam, H, Koefod, P, Melle, I, Steen, VM, Andreassen, OA & Djurovic, S 2010, 'Association study of PDE4B gene variants in Scandinavian schizophrenia and bipolar disorder multicenter case-control samples', American Journal of Medical Genetics. Part B: Neuropsychiatric Genetics, vol. 153B, no. 1, pp. 86-96. https://doi.org/10.1002/ajmg.b.30958

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title = "Association study of PDE4B gene variants in Scandinavian schizophrenia and bipolar disorder multicenter case-control samples",

abstract = "The phosphodiesterase 4B (PDE4B), which is involved in cognitive function in animal models, is a candidate susceptibility gene for schizophrenia (SZ) and bipolar disorder (BP). Variations in PDE4B have previously been associated with SZ, with a suggested gender-specific effect.Wehave genotyped and analyzed 40 and 72 tagging single nucleotide polymorphisms (tagSNPs) in SZ and BP multicenter samples, respectively, from the Scandinavian Collaboration on Psychiatric Etiology (SCOPE), involving 837 SZ cases and 1,473 controls plus 594 BP cases and 1,421 partly overlapping controls. Six and 16 tagSNPs were nominally associated (0.0005≤P≤0.05) with SZ and BP, respectively, in the combined samples or in gender-specific subgroups. None of these findings remained significant after correction for multiple testing. However, a number of tagSNPs found to be nominally associated with SZ and BP were located in a high LD region spanning the splice site of PDE4B3, an isoform with altered brain expression in BP patients. Four tagSNPs were associated with SZ in women, but none in men, in agreement with the previously reported gender-specific effect. Proxies of two nominally associated SNPs in the SZ sample were also associated with BP, but the genotypic effect (i.e., homozygosity for the minor allele), pointed in opposite directions. Finally, four SNPs were found to be associated with Positive And Negative Syndrome Scale (PANSS) positive symptom scores in a subgroup of SZ patients (n=153) or SZ female patients (n=70). Further studies are needed to evaluate the implicated PDE4B region of interest, for potential involvement in SZ and BP susceptibility.",

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AU - Kähler, Anna K

AU - Otnæss, Mona K

AU - Wirgenes, Katrine V

AU - Hansen, Thomas

AU - Jönsson, Erik G

AU - Agartz, Ingrid

AU - Hall, Håkan

AU - Werge, Thomas

AU - Morken, Gunnar

AU - Mors, Ole

AU - Mellerup, Erling

AU - Dam, Henrik

AU - Koefoed, Pernille

AU - Melle, Ingrid

AU - Steen, Vidar M

AU - Andreassen, Ole A

AU - Djurovic, Srdjan

AU - Kähler, Anna K

AU - Otnaess, Mona K

AU - Wirgenes, Katrine V

AU - Hansen, Thomas

AU - Jönsson, Erik G

AU - Agartz, Ingrid

AU - Hall, Håkan

AU - Werge, Thomas

AU - Morken, Gunnar

AU - Mors, Ole

AU - Mellerup, Erling

AU - Dam, Henrik

AU - Koefod, Pernille

AU - Melle, Ingrid

AU - Steen, Vidar M

AU - Andreassen, Ole A

AU - Djurovic, Srdjan

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N2 - The phosphodiesterase 4B (PDE4B), which is involved in cognitive function in animal models, is a candidate susceptibility gene for schizophrenia (SZ) and bipolar disorder (BP). Variations in PDE4B have previously been associated with SZ, with a suggested gender-specific effect.Wehave genotyped and analyzed 40 and 72 tagging single nucleotide polymorphisms (tagSNPs) in SZ and BP multicenter samples, respectively, from the Scandinavian Collaboration on Psychiatric Etiology (SCOPE), involving 837 SZ cases and 1,473 controls plus 594 BP cases and 1,421 partly overlapping controls. Six and 16 tagSNPs were nominally associated (0.0005≤P≤0.05) with SZ and BP, respectively, in the combined samples or in gender-specific subgroups. None of these findings remained significant after correction for multiple testing. However, a number of tagSNPs found to be nominally associated with SZ and BP were located in a high LD region spanning the splice site of PDE4B3, an isoform with altered brain expression in BP patients. Four tagSNPs were associated with SZ in women, but none in men, in agreement with the previously reported gender-specific effect. Proxies of two nominally associated SNPs in the SZ sample were also associated with BP, but the genotypic effect (i.e., homozygosity for the minor allele), pointed in opposite directions. Finally, four SNPs were found to be associated with Positive And Negative Syndrome Scale (PANSS) positive symptom scores in a subgroup of SZ patients (n=153) or SZ female patients (n=70). Further studies are needed to evaluate the implicated PDE4B region of interest, for potential involvement in SZ and BP susceptibility.

AB - The phosphodiesterase 4B (PDE4B), which is involved in cognitive function in animal models, is a candidate susceptibility gene for schizophrenia (SZ) and bipolar disorder (BP). Variations in PDE4B have previously been associated with SZ, with a suggested gender-specific effect.Wehave genotyped and analyzed 40 and 72 tagging single nucleotide polymorphisms (tagSNPs) in SZ and BP multicenter samples, respectively, from the Scandinavian Collaboration on Psychiatric Etiology (SCOPE), involving 837 SZ cases and 1,473 controls plus 594 BP cases and 1,421 partly overlapping controls. Six and 16 tagSNPs were nominally associated (0.0005≤P≤0.05) with SZ and BP, respectively, in the combined samples or in gender-specific subgroups. None of these findings remained significant after correction for multiple testing. However, a number of tagSNPs found to be nominally associated with SZ and BP were located in a high LD region spanning the splice site of PDE4B3, an isoform with altered brain expression in BP patients. Four tagSNPs were associated with SZ in women, but none in men, in agreement with the previously reported gender-specific effect. Proxies of two nominally associated SNPs in the SZ sample were also associated with BP, but the genotypic effect (i.e., homozygosity for the minor allele), pointed in opposite directions. Finally, four SNPs were found to be associated with Positive And Negative Syndrome Scale (PANSS) positive symptom scores in a subgroup of SZ patients (n=153) or SZ female patients (n=70). Further studies are needed to evaluate the implicated PDE4B region of interest, for potential involvement in SZ and BP susceptibility.

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DO - 10.1002/ajmg.b.30958

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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

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ER -

Association study of PDE4B gene variants in Scandinavian schizophrenia and bipolar disorder multicenter case-control samples

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