Association study of 21 circadian genes with bipolar I disorder, schizoaffective disorder, and schizophrenia

Hader A. Mansour; Michael E. Talkowski; Joel Wood; Kodavali V. Chowdari; Lora McClain; Konasale Prasad; Debra Montrose; Andrea Fagiolini; Edward S. Friedman; Michael H. Allen; Charles L. Bowden; Joseph Calabrese; Rif S. El-Mallakh; Michael Escamilla; Stephen V. Faraone; Mark D. Fossey; Laszlo Gyulai; Jennifer M. Loftis; Peter Hauser; Terence A. Ketter; Lauren B. Marangell; David J. Miklowitz; Andrew A. Nierenberg; Jayendra Patel; Gary S. Sachs; Pamela Sklar; Jordan W. Smoller; Nan Laird; Matcheri Keshavan; Michael E. Thase; David Axelson; Boris Birmaher; David Lewis; Tim Monk; Ellen Frank; David J. Kupfer; Bernie Devlin; Vishwajit L. Nimgaonkar

doi:10.1111/j.1399-5618.2009.00756.x

Association study of 21 circadian genes with bipolar I disorder, schizoaffective disorder, and schizophrenia

Hader A. Mansour, Michael E. Talkowski, Joel Wood, Kodavali V. Chowdari, Lora McClain, Konasale Prasad, Debra Montrose, Andrea Fagiolini, Edward S. Friedman, Michael H. Allen, Charles L. Bowden, Joseph Calabrese, Rif S. El-Mallakh, Michael Escamilla, Stephen V. Faraone, Mark D. Fossey, Laszlo Gyulai, Jennifer M. Loftis, Peter Hauser, Terence A. KetterLauren B. Marangell, David J. Miklowitz, Andrew A. Nierenberg, Jayendra Patel, Gary S. Sachs, Pamela Sklar, Jordan W. Smoller, Nan Laird, Matcheri Keshavan, Michael E. Thase, David Axelson, Boris Birmaher, David Lewis, Tim Monk, Ellen Frank, David J. Kupfer, Bernie Devlin, Vishwajit L. Nimgaonkar

Psychiatry

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

132 Scopus citations

Abstract

Objective: Published studies suggest associations between circadian gene polymorphisms and bipolar I disorder (BPI), as well as schizoaffective disorder (SZA) and schizophrenia (SZ). The results are plausible, based on prior studies of circadian abnormalities. As replications have not been attempted uniformly, we evaluated representative, common polymorphisms in all three disorders. Methods: We assayed 276 publicly available 'tag' single nucleotide polymorphisms (SNPs) at 21 circadian genes among 523 patients with BPI, 527 patients with SZ/SZA, and 477 screened adult controls. Detected associations were evaluated in relation to two published genome-wide association studies (GWAS). Results: Using gene-based tests, suggestive associations were noted between EGR3 and BPI (p = 0.017), and between NPAS2 and SZ/SZA (p = 0.034). Three SNPs were associated with both sets of disorders (NPAS2: rs13025524 and rs11123857; RORB: rs10491929; p < 0.05). None of the associations remained significant following corrections for multiple comparisons. Approximately 15% of the analyzed SNPs overlapped with an independent study that conducted GWAS for BPI; suggestive overlap between the GWAS analyses and ours was noted at ARNTL. Conclusions: Several suggestive, novel associations were detected with circadian genes and BPI and SZ/SZA, but the present analyses do not support associations with common polymorphisms that confer risk with odds ratios greater than 1.5. Additional analyses using adequately powered samples are warranted to further evaluate these results.

Original language	English (US)
Pages (from-to)	701-710
Number of pages	10
Journal	Bipolar Disorders
Volume	11
Issue number	7
DOIs	https://doi.org/10.1111/j.1399-5618.2009.00756.x
State	Published - Nov 2009

Keywords

Association
Bipolar disorder
Circadian
Gene
Schizoaffective disorder
Schizophrenia

ASJC Scopus subject areas

Psychiatry and Mental health
Biological Psychiatry

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10.1111/j.1399-5618.2009.00756.x

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Mansour, H. A., Talkowski, M. E., Wood, J., Chowdari, K. V., McClain, L., Prasad, K., Montrose, D., Fagiolini, A., Friedman, E. S., Allen, M. H., Bowden, C. L., Calabrese, J., El-Mallakh, R. S., Escamilla, M., Faraone, S. V., Fossey, M. D., Gyulai, L., Loftis, J. M., Hauser, P., ... Nimgaonkar, V. L. (2009). Association study of 21 circadian genes with bipolar I disorder, schizoaffective disorder, and schizophrenia. Bipolar Disorders, 11(7), 701-710. https://doi.org/10.1111/j.1399-5618.2009.00756.x

Mansour, HA, Talkowski, ME, Wood, J, Chowdari, KV, McClain, L, Prasad, K, Montrose, D, Fagiolini, A, Friedman, ES, Allen, MH, Bowden, CL, Calabrese, J, El-Mallakh, RS, Escamilla, M, Faraone, SV, Fossey, MD, Gyulai, L, Loftis, JM, Hauser, P, Ketter, TA, Marangell, LB, Miklowitz, DJ, Nierenberg, AA, Patel, J, Sachs, GS, Sklar, P, Smoller, JW, Laird, N, Keshavan, M, Thase, ME, Axelson, D, Birmaher, B, Lewis, D, Monk, T, Frank, E, Kupfer, DJ, Devlin, B & Nimgaonkar, VL 2009, 'Association study of 21 circadian genes with bipolar I disorder, schizoaffective disorder, and schizophrenia', Bipolar Disorders, vol. 11, no. 7, pp. 701-710. https://doi.org/10.1111/j.1399-5618.2009.00756.x

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title = "Association study of 21 circadian genes with bipolar I disorder, schizoaffective disorder, and schizophrenia",

abstract = "Objective: Published studies suggest associations between circadian gene polymorphisms and bipolar I disorder (BPI), as well as schizoaffective disorder (SZA) and schizophrenia (SZ). The results are plausible, based on prior studies of circadian abnormalities. As replications have not been attempted uniformly, we evaluated representative, common polymorphisms in all three disorders. Methods: We assayed 276 publicly available 'tag' single nucleotide polymorphisms (SNPs) at 21 circadian genes among 523 patients with BPI, 527 patients with SZ/SZA, and 477 screened adult controls. Detected associations were evaluated in relation to two published genome-wide association studies (GWAS). Results: Using gene-based tests, suggestive associations were noted between EGR3 and BPI (p = 0.017), and between NPAS2 and SZ/SZA (p = 0.034). Three SNPs were associated with both sets of disorders (NPAS2: rs13025524 and rs11123857; RORB: rs10491929; p < 0.05). None of the associations remained significant following corrections for multiple comparisons. Approximately 15% of the analyzed SNPs overlapped with an independent study that conducted GWAS for BPI; suggestive overlap between the GWAS analyses and ours was noted at ARNTL. Conclusions: Several suggestive, novel associations were detected with circadian genes and BPI and SZ/SZA, but the present analyses do not support associations with common polymorphisms that confer risk with odds ratios greater than 1.5. Additional analyses using adequately powered samples are warranted to further evaluate these results.",

keywords = "Association, Bipolar disorder, Circadian, Gene, Schizoaffective disorder, Schizophrenia",

author = "Mansour, {Hader A.} and Talkowski, {Michael E.} and Joel Wood and Chowdari, {Kodavali V.} and Lora McClain and Konasale Prasad and Debra Montrose and Andrea Fagiolini and Friedman, {Edward S.} and Allen, {Michael H.} and Bowden, {Charles L.} and Joseph Calabrese and El-Mallakh, {Rif S.} and Michael Escamilla and Faraone, {Stephen V.} and Fossey, {Mark D.} and Laszlo Gyulai and Loftis, {Jennifer M.} and Peter Hauser and Ketter, {Terence A.} and Marangell, {Lauren B.} and Miklowitz, {David J.} and Nierenberg, {Andrew A.} and Jayendra Patel and Sachs, {Gary S.} and Pamela Sklar and Smoller, {Jordan W.} and Nan Laird and Matcheri Keshavan and Thase, {Michael E.} and David Axelson and Boris Birmaher and David Lewis and Tim Monk and Ellen Frank and Kupfer, {David J.} and Bernie Devlin and Nimgaonkar, {Vishwajit L.}",

year = "2009",

month = nov,

doi = "10.1111/j.1399-5618.2009.00756.x",

language = "English (US)",

volume = "11",

pages = "701--710",

journal = "Bipolar Disorders",

issn = "1398-5647",

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number = "7",

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TY - JOUR

T1 - Association study of 21 circadian genes with bipolar I disorder, schizoaffective disorder, and schizophrenia

AU - Mansour, Hader A.

AU - Talkowski, Michael E.

AU - Wood, Joel

AU - Chowdari, Kodavali V.

AU - McClain, Lora

AU - Prasad, Konasale

AU - Montrose, Debra

AU - Fagiolini, Andrea

AU - Friedman, Edward S.

AU - Allen, Michael H.

AU - Bowden, Charles L.

AU - Calabrese, Joseph

AU - El-Mallakh, Rif S.

AU - Escamilla, Michael

AU - Faraone, Stephen V.

AU - Fossey, Mark D.

AU - Gyulai, Laszlo

AU - Loftis, Jennifer M.

AU - Hauser, Peter

AU - Ketter, Terence A.

AU - Marangell, Lauren B.

AU - Miklowitz, David J.

AU - Nierenberg, Andrew A.

AU - Patel, Jayendra

AU - Sachs, Gary S.

AU - Sklar, Pamela

AU - Smoller, Jordan W.

AU - Laird, Nan

AU - Keshavan, Matcheri

AU - Thase, Michael E.

AU - Axelson, David

AU - Birmaher, Boris

AU - Lewis, David

AU - Monk, Tim

AU - Frank, Ellen

AU - Kupfer, David J.

AU - Devlin, Bernie

AU - Nimgaonkar, Vishwajit L.

PY - 2009/11

Y1 - 2009/11

N2 - Objective: Published studies suggest associations between circadian gene polymorphisms and bipolar I disorder (BPI), as well as schizoaffective disorder (SZA) and schizophrenia (SZ). The results are plausible, based on prior studies of circadian abnormalities. As replications have not been attempted uniformly, we evaluated representative, common polymorphisms in all three disorders. Methods: We assayed 276 publicly available 'tag' single nucleotide polymorphisms (SNPs) at 21 circadian genes among 523 patients with BPI, 527 patients with SZ/SZA, and 477 screened adult controls. Detected associations were evaluated in relation to two published genome-wide association studies (GWAS). Results: Using gene-based tests, suggestive associations were noted between EGR3 and BPI (p = 0.017), and between NPAS2 and SZ/SZA (p = 0.034). Three SNPs were associated with both sets of disorders (NPAS2: rs13025524 and rs11123857; RORB: rs10491929; p < 0.05). None of the associations remained significant following corrections for multiple comparisons. Approximately 15% of the analyzed SNPs overlapped with an independent study that conducted GWAS for BPI; suggestive overlap between the GWAS analyses and ours was noted at ARNTL. Conclusions: Several suggestive, novel associations were detected with circadian genes and BPI and SZ/SZA, but the present analyses do not support associations with common polymorphisms that confer risk with odds ratios greater than 1.5. Additional analyses using adequately powered samples are warranted to further evaluate these results.

AB - Objective: Published studies suggest associations between circadian gene polymorphisms and bipolar I disorder (BPI), as well as schizoaffective disorder (SZA) and schizophrenia (SZ). The results are plausible, based on prior studies of circadian abnormalities. As replications have not been attempted uniformly, we evaluated representative, common polymorphisms in all three disorders. Methods: We assayed 276 publicly available 'tag' single nucleotide polymorphisms (SNPs) at 21 circadian genes among 523 patients with BPI, 527 patients with SZ/SZA, and 477 screened adult controls. Detected associations were evaluated in relation to two published genome-wide association studies (GWAS). Results: Using gene-based tests, suggestive associations were noted between EGR3 and BPI (p = 0.017), and between NPAS2 and SZ/SZA (p = 0.034). Three SNPs were associated with both sets of disorders (NPAS2: rs13025524 and rs11123857; RORB: rs10491929; p < 0.05). None of the associations remained significant following corrections for multiple comparisons. Approximately 15% of the analyzed SNPs overlapped with an independent study that conducted GWAS for BPI; suggestive overlap between the GWAS analyses and ours was noted at ARNTL. Conclusions: Several suggestive, novel associations were detected with circadian genes and BPI and SZ/SZA, but the present analyses do not support associations with common polymorphisms that confer risk with odds ratios greater than 1.5. Additional analyses using adequately powered samples are warranted to further evaluate these results.

KW - Association

KW - Bipolar disorder

KW - Circadian

KW - Gene

KW - Schizoaffective disorder

KW - Schizophrenia

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Association study of 21 circadian genes with bipolar I disorder, schizoaffective disorder, and schizophrenia

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Keywords

ASJC Scopus subject areas

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