DISC1 association, heterogeneity and interplay in schizophrenia and bipolar disorder

W. Hennah, P. Thomson, A. McQuillin, N. Bass, Anu Loukola, A. Anjorin, D. Blackwood, D. Curtis, I. J. Deary, S. E. Harris, E. T. Isometsa, J. Lawrence, J. Lonnqvist, W. Muir, A. Palotie, T. Partonen, T. Paunio, E. Pylkko, M. Robinson, P. SoronenK. Suominen, J. Suvisaari, S. Thirumalai, D. St Clair, H. Gurling, L. Peltonen, D. Porteous

Tutkimustuotos: ArtikkelijulkaisuArtikkeliTieteellinenvertaisarvioitu

Kuvaus

"Disrupted in schizophrenia 1 (DISC1) has been associated with risk of schizophrenia, schizoaffective disorder, bipolar disorder, major depression, autism and Asperger syndrome, but apart from in the original translocation family, true causal variants have yet to be confirmed. Here we report a harmonized association study for DISC1 in European cohorts of schizophrenia and bipolar disorder. We identify regions of significant association, demonstrate allele frequency heterogeneity and provide preliminary evidence for modifying interplay between variants. Whereas no associations survived permutation analysis in the combined data set, significant corrected associations were observed for bipolar disorder at rs1538979 in the Finnish cohorts (uncorrected P = 0.00020; corrected P = 0.016; odds ratio = 2.73 +/- 95% confidence interval (CI) 1.42-5.27) and at rs821577 in the London cohort (uncorrected P = 0.00070; corrected P = 0.040; odds ratio = 1.64 +/- 95% CI 1.23-2.19). The rs821577 single nucleotide polymorphism (SNP) showed evidence for increased risk within the combined European cohorts (odds ratio = 1.27 +/- 95% CI 1.07-1.51), even though significant corrected association was not detected (uncorrected P = 0.0058; corrected P = 0.28). After conditioning the European data set on the two risk alleles, reanalysis revealed a third significant SNP association (uncorrected P = 0.00050; corrected P = 0.025). This SNP showed evidence for interplay, either increasing or decreasing risk, dependent upon the presence or absence of rs1538979 or rs821577. These findings provide further support for the role of DISC1 in psychiatric illness and demonstrate the presence of locus heterogeneity, with the effect that clinically relevant genetic variants may go undetected by standard analysis of combined cohorts. Molecular Psychiatry (2009) 14, 865-873; doi: 10.1038/mp.2008.22; published online 4 March 2008"
Alkuperäiskielienglanti
LehtiMolecular Psychiatry
Vuosikerta14
Numero9
Sivut865-873
Sivumäärä9
ISSN1359-4184
DOI - pysyväislinkit
TilaJulkaistu - 2009
OKM-julkaisutyyppiA1 Alkuperäisartikkeli tieteellisessä aikakauslehdessä, vertaisarvioitu

Lainaa tätä

Hennah, W. ; Thomson, P. ; McQuillin, A. ; Bass, N. ; Loukola, Anu ; Anjorin, A. ; Blackwood, D. ; Curtis, D. ; Deary, I. J. ; Harris, S. E. ; Isometsa, E. T. ; Lawrence, J. ; Lonnqvist, J. ; Muir, W. ; Palotie, A. ; Partonen, T. ; Paunio, T. ; Pylkko, E. ; Robinson, M. ; Soronen, P. ; Suominen, K. ; Suvisaari, J. ; Thirumalai, S. ; St Clair, D. ; Gurling, H. ; Peltonen, L. ; Porteous, D. / DISC1 association, heterogeneity and interplay in schizophrenia and bipolar disorder. Julkaisussa: Molecular Psychiatry. 2009 ; Vuosikerta 14, Nro 9. Sivut 865-873.
@article{773b179e5a344a928b8185673e2efc34,
title = "DISC1 association, heterogeneity and interplay in schizophrenia and bipolar disorder",
abstract = "{"}Disrupted in schizophrenia 1 (DISC1) has been associated with risk of schizophrenia, schizoaffective disorder, bipolar disorder, major depression, autism and Asperger syndrome, but apart from in the original translocation family, true causal variants have yet to be confirmed. Here we report a harmonized association study for DISC1 in European cohorts of schizophrenia and bipolar disorder. We identify regions of significant association, demonstrate allele frequency heterogeneity and provide preliminary evidence for modifying interplay between variants. Whereas no associations survived permutation analysis in the combined data set, significant corrected associations were observed for bipolar disorder at rs1538979 in the Finnish cohorts (uncorrected P = 0.00020; corrected P = 0.016; odds ratio = 2.73 +/- 95{\%} confidence interval (CI) 1.42-5.27) and at rs821577 in the London cohort (uncorrected P = 0.00070; corrected P = 0.040; odds ratio = 1.64 +/- 95{\%} CI 1.23-2.19). The rs821577 single nucleotide polymorphism (SNP) showed evidence for increased risk within the combined European cohorts (odds ratio = 1.27 +/- 95{\%} CI 1.07-1.51), even though significant corrected association was not detected (uncorrected P = 0.0058; corrected P = 0.28). After conditioning the European data set on the two risk alleles, reanalysis revealed a third significant SNP association (uncorrected P = 0.00050; corrected P = 0.025). This SNP showed evidence for interplay, either increasing or decreasing risk, dependent upon the presence or absence of rs1538979 or rs821577. These findings provide further support for the role of DISC1 in psychiatric illness and demonstrate the presence of locus heterogeneity, with the effect that clinically relevant genetic variants may go undetected by standard analysis of combined cohorts. Molecular Psychiatry (2009) 14, 865-873; doi: 10.1038/mp.2008.22; published online 4 March 2008{"}",
author = "W. Hennah and P. Thomson and A. McQuillin and N. Bass and Anu Loukola and A. Anjorin and D. Blackwood and D. Curtis and Deary, {I. J.} and Harris, {S. E.} and Isometsa, {E. T.} and J. Lawrence and J. Lonnqvist and W. Muir and A. Palotie and T. Partonen and T. Paunio and E. Pylkko and M. Robinson and P. Soronen and K. Suominen and J. Suvisaari and S. Thirumalai and {St Clair}, D. and H. Gurling and L. Peltonen and D. Porteous",
year = "2009",
doi = "10.1038/mp.2008.22",
language = "English",
volume = "14",
pages = "865--873",
journal = "Molecular Psychiatry",
issn = "1359-4184",
publisher = "Nature Publishing Group",
number = "9",

}

Hennah, W, Thomson, P, McQuillin, A, Bass, N, Loukola, A, Anjorin, A, Blackwood, D, Curtis, D, Deary, IJ, Harris, SE, Isometsa, ET, Lawrence, J, Lonnqvist, J, Muir, W, Palotie, A, Partonen, T, Paunio, T, Pylkko, E, Robinson, M, Soronen, P, Suominen, K, Suvisaari, J, Thirumalai, S, St Clair, D, Gurling, H, Peltonen, L & Porteous, D 2009, 'DISC1 association, heterogeneity and interplay in schizophrenia and bipolar disorder', Molecular Psychiatry, Vuosikerta 14, Nro 9, Sivut 865-873. https://doi.org/10.1038/mp.2008.22

DISC1 association, heterogeneity and interplay in schizophrenia and bipolar disorder. / Hennah, W.; Thomson, P.; McQuillin, A.; Bass, N.; Loukola, Anu; Anjorin, A.; Blackwood, D.; Curtis, D.; Deary, I. J.; Harris, S. E.; Isometsa, E. T.; Lawrence, J.; Lonnqvist, J.; Muir, W.; Palotie, A.; Partonen, T.; Paunio, T.; Pylkko, E.; Robinson, M.; Soronen, P.; Suominen, K.; Suvisaari, J.; Thirumalai, S.; St Clair, D.; Gurling, H.; Peltonen, L.; Porteous, D.

julkaisussa: Molecular Psychiatry, Vuosikerta 14, Nro 9, 2009, s. 865-873.

Tutkimustuotos: ArtikkelijulkaisuArtikkeliTieteellinenvertaisarvioitu

TY - JOUR

T1 - DISC1 association, heterogeneity and interplay in schizophrenia and bipolar disorder

AU - Hennah, W.

AU - Thomson, P.

AU - McQuillin, A.

AU - Bass, N.

AU - Loukola, Anu

AU - Anjorin, A.

AU - Blackwood, D.

AU - Curtis, D.

AU - Deary, I. J.

AU - Harris, S. E.

AU - Isometsa, E. T.

AU - Lawrence, J.

AU - Lonnqvist, J.

AU - Muir, W.

AU - Palotie, A.

AU - Partonen, T.

AU - Paunio, T.

AU - Pylkko, E.

AU - Robinson, M.

AU - Soronen, P.

AU - Suominen, K.

AU - Suvisaari, J.

AU - Thirumalai, S.

AU - St Clair, D.

AU - Gurling, H.

AU - Peltonen, L.

AU - Porteous, D.

PY - 2009

Y1 - 2009

N2 - "Disrupted in schizophrenia 1 (DISC1) has been associated with risk of schizophrenia, schizoaffective disorder, bipolar disorder, major depression, autism and Asperger syndrome, but apart from in the original translocation family, true causal variants have yet to be confirmed. Here we report a harmonized association study for DISC1 in European cohorts of schizophrenia and bipolar disorder. We identify regions of significant association, demonstrate allele frequency heterogeneity and provide preliminary evidence for modifying interplay between variants. Whereas no associations survived permutation analysis in the combined data set, significant corrected associations were observed for bipolar disorder at rs1538979 in the Finnish cohorts (uncorrected P = 0.00020; corrected P = 0.016; odds ratio = 2.73 +/- 95% confidence interval (CI) 1.42-5.27) and at rs821577 in the London cohort (uncorrected P = 0.00070; corrected P = 0.040; odds ratio = 1.64 +/- 95% CI 1.23-2.19). The rs821577 single nucleotide polymorphism (SNP) showed evidence for increased risk within the combined European cohorts (odds ratio = 1.27 +/- 95% CI 1.07-1.51), even though significant corrected association was not detected (uncorrected P = 0.0058; corrected P = 0.28). After conditioning the European data set on the two risk alleles, reanalysis revealed a third significant SNP association (uncorrected P = 0.00050; corrected P = 0.025). This SNP showed evidence for interplay, either increasing or decreasing risk, dependent upon the presence or absence of rs1538979 or rs821577. These findings provide further support for the role of DISC1 in psychiatric illness and demonstrate the presence of locus heterogeneity, with the effect that clinically relevant genetic variants may go undetected by standard analysis of combined cohorts. Molecular Psychiatry (2009) 14, 865-873; doi: 10.1038/mp.2008.22; published online 4 March 2008"

AB - "Disrupted in schizophrenia 1 (DISC1) has been associated with risk of schizophrenia, schizoaffective disorder, bipolar disorder, major depression, autism and Asperger syndrome, but apart from in the original translocation family, true causal variants have yet to be confirmed. Here we report a harmonized association study for DISC1 in European cohorts of schizophrenia and bipolar disorder. We identify regions of significant association, demonstrate allele frequency heterogeneity and provide preliminary evidence for modifying interplay between variants. Whereas no associations survived permutation analysis in the combined data set, significant corrected associations were observed for bipolar disorder at rs1538979 in the Finnish cohorts (uncorrected P = 0.00020; corrected P = 0.016; odds ratio = 2.73 +/- 95% confidence interval (CI) 1.42-5.27) and at rs821577 in the London cohort (uncorrected P = 0.00070; corrected P = 0.040; odds ratio = 1.64 +/- 95% CI 1.23-2.19). The rs821577 single nucleotide polymorphism (SNP) showed evidence for increased risk within the combined European cohorts (odds ratio = 1.27 +/- 95% CI 1.07-1.51), even though significant corrected association was not detected (uncorrected P = 0.0058; corrected P = 0.28). After conditioning the European data set on the two risk alleles, reanalysis revealed a third significant SNP association (uncorrected P = 0.00050; corrected P = 0.025). This SNP showed evidence for interplay, either increasing or decreasing risk, dependent upon the presence or absence of rs1538979 or rs821577. These findings provide further support for the role of DISC1 in psychiatric illness and demonstrate the presence of locus heterogeneity, with the effect that clinically relevant genetic variants may go undetected by standard analysis of combined cohorts. Molecular Psychiatry (2009) 14, 865-873; doi: 10.1038/mp.2008.22; published online 4 March 2008"

U2 - 10.1038/mp.2008.22

DO - 10.1038/mp.2008.22

M3 - Article

VL - 14

SP - 865

EP - 873

JO - Molecular Psychiatry

JF - Molecular Psychiatry

SN - 1359-4184

IS - 9

ER -