Replication Study and Meta-Analysis in European Samples Supports Association of the 3p21.1 Locus with Bipolar Disorder

Evangelos Vassos; Stacy Steinberg; Sven Cichon; Gerome Breen; Engilbert Sigurdsson; Ole A. Andreassen; Srdjan Djurovic; Gunnar Morken; Maria Grigoroiu-Serbanescu; Carmen C. Diaconu; Piotr M. Czerski; Joanna Hauser; Gulja Babadjanova; Lilia I. Abramova; Thomas W. Muehleisen; Markus M. Noethen; Marcella Rietschel; Peter McGuffin; David St Clair; Omar Gustafsson; Ingrid Melle; Olli P. H. Pietilainen; Mirella Ruggeri; Sarah Tosato; Thomas Werge; Roel A. Ophoff; Dan Rujescu; Anders D. Borglum; Ole Mors; Preben B. Mortensen; Ditte Demontis; Mads V. Hollegaard; Ruud van Winkel; Gunter Kenis; Marc De Hert; Janos M. Rethelyi; Istvan Bitter; I. Alex Rubino; Vera Golimbet; Lambertus A. Kiemeney; Leonard H. van den Berg; Barbara Franke; Erik G. Jonsson; Anne Farmer; Hreinn Stefansson; Kari Stefansson; David A. Collier; Grp Consortium

doi:10.1016/j.biopsych.2012.02.040

Replication Study and Meta-Analysis in European Samples Supports Association of the 3p21.1 Locus with Bipolar Disorder

Evangelos Vassos, Stacy Steinberg, Sven Cichon, Gerome Breen, Engilbert Sigurdsson, Ole A. Andreassen, Srdjan Djurovic, Gunnar Morken, Maria Grigoroiu-Serbanescu, Carmen C. Diaconu, Piotr M. Czerski, Joanna Hauser, Gulja Babadjanova, Lilia I. Abramova, Thomas W. Muehleisen, Markus M. Noethen, Marcella Rietschel, Peter McGuffin, David St Clair, Omar GustafssonIngrid Melle, Olli P. H. Pietilainen, Mirella Ruggeri, Sarah Tosato, Thomas Werge, Roel A. Ophoff, Dan Rujescu, Anders D. Borglum, Ole Mors, Preben B. Mortensen, Ditte Demontis, Mads V. Hollegaard, Ruud van Winkel, Gunter Kenis, Marc De Hert, Janos M. Rethelyi, Istvan Bitter, I. Alex Rubino, Vera Golimbet, Lambertus A. Kiemeney, Leonard H. van den Berg, Barbara Franke, Erik G. Jonsson, Anne Farmer, Hreinn Stefansson, Kari Stefansson, David A. Collier, Grp Consortium

Research output: Contribution to journal › Article › peer-review

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Abstract

Background: Common genetic polymorphisms at chromosome 3p21.1, including rs2251219 in polybromo 1 (PBRM1), have been implicated in susceptibility to bipolar affective disorder (BP) through genome-wide association studies. Subsequent studies have suggested that this is also a risk locus for other psychiatric phenotypes, including major depression and schizophrenia.

Methods: To replicate the association, we studied 2562 cases with BP and 25,439 control subjects collected from seven cohorts with either genome-wide association or individual genotyping of rs2251219 and tagging single nucleotide polymorphisms across the PBRM1 gene. Results from the different case-control groups were combined with the inverse variance weighting method.

Results: In our dataset, rs2251219 was associated with BP (odds ratio [OR] = .89, p = .003), and meta-analysis of previously published data with our nonoverlapping new data confirmed genome-wide significant association (OR = .875, p = 2.68 x 10(-9)). Genotypic data from the SGENE-plus consortium were used to examine the association of the same variant with schizophrenia in an overall sample of 8794 cases and 25,457 control subjects, but this was not statistically significant (OR = .97, p = .21).

Conclusions: There is strong evidence of association of rs2251219 with BP. However, our data do not support association of this marker with schizophrenia. Because the region of association has high linkage disequilibrium, forming a large haplotype block across many genes, it is not clear which gene is causally implicated in the disorder.

Original language	English
Article number	N/A
Pages (from-to)	645-650
Number of pages	6
Journal	Biological psychiatry
Volume	72
Issue number	8
DOIs	https://doi.org/10.1016/j.biopsych.2012.02.040
Publication status	Published - 15 Oct 2012

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Vassos, E., Steinberg, S., Cichon, S., Breen, G., Sigurdsson, E., Andreassen, O. A., Djurovic, S., Morken, G., Grigoroiu-Serbanescu, M., Diaconu, C. C., Czerski, P. M., Hauser, J., Babadjanova, G., Abramova, L. I., Muehleisen, T. W., Noethen, M. M., Rietschel, M., McGuffin, P., St Clair, D., ... Grp Consortium (2012). Replication Study and Meta-Analysis in European Samples Supports Association of the 3p21.1 Locus with Bipolar Disorder. Biological psychiatry, 72(8), 645-650. Article N/A. https://doi.org/10.1016/j.biopsych.2012.02.040

@article{439cb49cdeb94ed68e8eacfeb48ddbc4,

title = "Replication Study and Meta-Analysis in European Samples Supports Association of the 3p21.1 Locus with Bipolar Disorder",

abstract = "Background: Common genetic polymorphisms at chromosome 3p21.1, including rs2251219 in polybromo 1 (PBRM1), have been implicated in susceptibility to bipolar affective disorder (BP) through genome-wide association studies. Subsequent studies have suggested that this is also a risk locus for other psychiatric phenotypes, including major depression and schizophrenia. Methods: To replicate the association, we studied 2562 cases with BP and 25,439 control subjects collected from seven cohorts with either genome-wide association or individual genotyping of rs2251219 and tagging single nucleotide polymorphisms across the PBRM1 gene. Results from the different case-control groups were combined with the inverse variance weighting method. Results: In our dataset, rs2251219 was associated with BP (odds ratio [OR] = .89, p = .003), and meta-analysis of previously published data with our nonoverlapping new data confirmed genome-wide significant association (OR = .875, p = 2.68 x 10(-9)). Genotypic data from the SGENE-plus consortium were used to examine the association of the same variant with schizophrenia in an overall sample of 8794 cases and 25,457 control subjects, but this was not statistically significant (OR = .97, p = .21). Conclusions: There is strong evidence of association of rs2251219 with BP. However, our data do not support association of this marker with schizophrenia. Because the region of association has high linkage disequilibrium, forming a large haplotype block across many genes, it is not clear which gene is causally implicated in the disorder.",

author = "Evangelos Vassos and Stacy Steinberg and Sven Cichon and Gerome Breen and Engilbert Sigurdsson and Andreassen, {Ole A.} and Srdjan Djurovic and Gunnar Morken and Maria Grigoroiu-Serbanescu and Diaconu, {Carmen C.} and Czerski, {Piotr M.} and Joanna Hauser and Gulja Babadjanova and Abramova, {Lilia I.} and Muehleisen, {Thomas W.} and Noethen, {Markus M.} and Marcella Rietschel and Peter McGuffin and {St Clair}, David and Omar Gustafsson and Ingrid Melle and Pietilainen, {Olli P. H.} and Mirella Ruggeri and Sarah Tosato and Thomas Werge and Ophoff, {Roel A.} and Dan Rujescu and Borglum, {Anders D.} and Ole Mors and Mortensen, {Preben B.} and Ditte Demontis and Hollegaard, {Mads V.} and {van Winkel}, Ruud and Gunter Kenis and {De Hert}, Marc and Rethelyi, {Janos M.} and Istvan Bitter and Rubino, {I. Alex} and Vera Golimbet and Kiemeney, {Lambertus A.} and {van den Berg}, {Leonard H.} and Barbara Franke and Jonsson, {Erik G.} and Anne Farmer and Hreinn Stefansson and Kari Stefansson and Collier, {David A.} and {Grp Consortium}",

year = "2012",

month = oct,

day = "15",

doi = "10.1016/j.biopsych.2012.02.040",

language = "English",

volume = "72",

pages = "645--650",

journal = "Biological psychiatry",

issn = "0006-3223",

publisher = "Elsevier",

number = "8",

}

Vassos, E, Steinberg, S, Cichon, S, Breen, G, Sigurdsson, E, Andreassen, OA, Djurovic, S, Morken, G, Grigoroiu-Serbanescu, M, Diaconu, CC, Czerski, PM, Hauser, J, Babadjanova, G, Abramova, LI, Muehleisen, TW, Noethen, MM, Rietschel, M, McGuffin, P, St Clair, D, Gustafsson, O, Melle, I, Pietilainen, OPH, Ruggeri, M, Tosato, S, Werge, T, Ophoff, RA, Rujescu, D, Borglum, AD, Mors, O, Mortensen, PB, Demontis, D, Hollegaard, MV, van Winkel, R, Kenis, G, De Hert, M, Rethelyi, JM, Bitter, I, Rubino, IA, Golimbet, V, Kiemeney, LA, van den Berg, LH, Franke, B, Jonsson, EG, Farmer, A, Stefansson, H, Stefansson, K, Collier, DA & Grp Consortium 2012, 'Replication Study and Meta-Analysis in European Samples Supports Association of the 3p21.1 Locus with Bipolar Disorder', Biological psychiatry, vol. 72, no. 8, N/A, pp. 645-650. https://doi.org/10.1016/j.biopsych.2012.02.040

TY - JOUR

T1 - Replication Study and Meta-Analysis in European Samples Supports Association of the 3p21.1 Locus with Bipolar Disorder

AU - Vassos, Evangelos

AU - Steinberg, Stacy

AU - Cichon, Sven

AU - Breen, Gerome

AU - Sigurdsson, Engilbert

AU - Andreassen, Ole A.

AU - Djurovic, Srdjan

AU - Morken, Gunnar

AU - Grigoroiu-Serbanescu, Maria

AU - Diaconu, Carmen C.

AU - Czerski, Piotr M.

AU - Hauser, Joanna

AU - Babadjanova, Gulja

AU - Abramova, Lilia I.

AU - Muehleisen, Thomas W.

AU - Noethen, Markus M.

AU - Rietschel, Marcella

AU - McGuffin, Peter

AU - St Clair, David

AU - Gustafsson, Omar

AU - Melle, Ingrid

AU - Pietilainen, Olli P. H.

AU - Ruggeri, Mirella

AU - Tosato, Sarah

AU - Werge, Thomas

AU - Ophoff, Roel A.

AU - Rujescu, Dan

AU - Borglum, Anders D.

AU - Mors, Ole

AU - Mortensen, Preben B.

AU - Demontis, Ditte

AU - Hollegaard, Mads V.

AU - van Winkel, Ruud

AU - Kenis, Gunter

AU - De Hert, Marc

AU - Rethelyi, Janos M.

AU - Bitter, Istvan

AU - Rubino, I. Alex

AU - Golimbet, Vera

AU - Kiemeney, Lambertus A.

AU - van den Berg, Leonard H.

AU - Franke, Barbara

AU - Jonsson, Erik G.

AU - Farmer, Anne

AU - Stefansson, Hreinn

AU - Stefansson, Kari

AU - Collier, David A.

AU - Grp Consortium

PY - 2012/10/15

Y1 - 2012/10/15

N2 - Background: Common genetic polymorphisms at chromosome 3p21.1, including rs2251219 in polybromo 1 (PBRM1), have been implicated in susceptibility to bipolar affective disorder (BP) through genome-wide association studies. Subsequent studies have suggested that this is also a risk locus for other psychiatric phenotypes, including major depression and schizophrenia. Methods: To replicate the association, we studied 2562 cases with BP and 25,439 control subjects collected from seven cohorts with either genome-wide association or individual genotyping of rs2251219 and tagging single nucleotide polymorphisms across the PBRM1 gene. Results from the different case-control groups were combined with the inverse variance weighting method. Results: In our dataset, rs2251219 was associated with BP (odds ratio [OR] = .89, p = .003), and meta-analysis of previously published data with our nonoverlapping new data confirmed genome-wide significant association (OR = .875, p = 2.68 x 10(-9)). Genotypic data from the SGENE-plus consortium were used to examine the association of the same variant with schizophrenia in an overall sample of 8794 cases and 25,457 control subjects, but this was not statistically significant (OR = .97, p = .21). Conclusions: There is strong evidence of association of rs2251219 with BP. However, our data do not support association of this marker with schizophrenia. Because the region of association has high linkage disequilibrium, forming a large haplotype block across many genes, it is not clear which gene is causally implicated in the disorder.

AB - Background: Common genetic polymorphisms at chromosome 3p21.1, including rs2251219 in polybromo 1 (PBRM1), have been implicated in susceptibility to bipolar affective disorder (BP) through genome-wide association studies. Subsequent studies have suggested that this is also a risk locus for other psychiatric phenotypes, including major depression and schizophrenia. Methods: To replicate the association, we studied 2562 cases with BP and 25,439 control subjects collected from seven cohorts with either genome-wide association or individual genotyping of rs2251219 and tagging single nucleotide polymorphisms across the PBRM1 gene. Results from the different case-control groups were combined with the inverse variance weighting method. Results: In our dataset, rs2251219 was associated with BP (odds ratio [OR] = .89, p = .003), and meta-analysis of previously published data with our nonoverlapping new data confirmed genome-wide significant association (OR = .875, p = 2.68 x 10(-9)). Genotypic data from the SGENE-plus consortium were used to examine the association of the same variant with schizophrenia in an overall sample of 8794 cases and 25,457 control subjects, but this was not statistically significant (OR = .97, p = .21). Conclusions: There is strong evidence of association of rs2251219 with BP. However, our data do not support association of this marker with schizophrenia. Because the region of association has high linkage disequilibrium, forming a large haplotype block across many genes, it is not clear which gene is causally implicated in the disorder.

U2 - 10.1016/j.biopsych.2012.02.040

DO - 10.1016/j.biopsych.2012.02.040

M3 - Article

SN - 0006-3223

VL - 72

SP - 645

EP - 650

JO - Biological psychiatry

JF - Biological psychiatry

IS - 8

M1 - N/A

ER -

Replication Study and Meta-Analysis in European Samples Supports Association of the 3p21.1 Locus with Bipolar Disorder

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