Family-based association of YWHAH in psychotic bipolar disorder

Deepak Grover, Ranjana Verma, Fernando S. Goes, Pamela L. Belmonte Mahon, Elliot S. Gershon, Francis J. McMahon, James B. Potash, F. J. McMahon, J. Steele, J. Pearl, L. Kassem, V. Lopez, T. Schulze, J. Potash, D. MacKinnon, E. Miller, J. Toolan, P. Zandi, S. Simpson, John Nurnberger & 64 others M. Miller, E. Bowman, T. Reich, A. Goate, J. Rice, J. R. DePaulo, S. Simpson, C. Stine, E. Gershon, D. Kazuba, E. Maxwell, J. Nurnberger, M. J. Miller, E. S. Bowman, N. L. Rau, P. R. Moe, N. Samavedy, R. El-Mallakh, H. Manji, D. A. Glitz, E. T. Meyer, C. Smiley, Tatiana Foroud, L. Flury, D. M. Dick, Howard Edenberg, J. Rice, T. Reich, A. Goate, L. Bierut, M. McInnis, J. R. DePaulo, D. F. MacKinnon, F. M. Mondimore, J. B. Potash, P. P. Zandi, D. Avramopoulos, J. Payne, W. Berrettini, W. Byerley, M. Vawter, W. Coryell, R. Crowe, E. Gershon, J. Badner, F. McMahon, C. Liu, A. Sanders, M. Caserta, S. Dinwiddie, T. Nguyen, D. Harakal, J. Kelsoe, R. McKinney, W. Scheftner, H. M. Kravitz, D. Marta, A. Vaughn-Brown, L. Bederow, F. McMahon, L. Kassem, S. Detera-Wadleigh, L. Austin, D. L. Murphy

Research output: Contribution to journalArticle

33 Citations (Scopus)

Abstract

YWHAH is a positional and functional candidate gene for both schizophrenia and bipolar disorder (BP). This gene has been previously shown to be associated with both disorders, and the chromosome location (22q12.3) has been repeatedly implicated in linkage studies for these disorders. It codes for thehsubtype of the 14-3-3 protein family, is expressed mainly in brain, and is involved in HPA axis regulation.Weinvestigated the association ofYWHAHwith BP in a large sample, consisting of 1211 subjects from 318 nuclear families including 554 affected offspring. We tested for association with the standard BP phenotype as well as subtypes defined by psychotic and mood-incongruent features. We genotyped five tag SNPs and the (GCCTGCA)n polymorphic locus present in this gene. Using a family-based association test, we found that rs2246704 was associated with BP (OR 1.31, P=0.03) and psychotic BP (OR=1.66, P=0.002). The polymorphic repeat and two other SNPs were also modestly associated with psychotic BP. We have provided additional evidence for association of variants in YWHAH with major mental illness. Additional association analyses of larger sample sets will be required to clarify the role of YWHAH in schizophrenia and BP. The use of clinical sub-phenotypes such as psychotic features or other potential schizophrenia/BP overlap variables including cognitive abnormalities and poor functioning might shed further light on the potential subtypes of illness most closely associated with genetic variation in YWHAH.

Original languageEnglish
Pages (from-to)977-983
Number of pages7
JournalAmerican Journal of Medical Genetics, Part B: Neuropsychiatric Genetics
Volume150
Issue number7
DOIs
StatePublished - Oct 5 2009

Fingerprint

Bipolar Disorder
Psychotic Disorders
Schizophrenia
Single Nucleotide Polymorphism
Chromosome Disorders
Genes
14-3-3 Proteins
Phenotype
Nuclear Family
Brain

Keywords

  • 14-3-3
  • Bipolar disorder
  • Psychosis
  • Schizophrenia
  • YWHAH

ASJC Scopus subject areas

  • Genetics(clinical)
  • Psychiatry and Mental health
  • Cellular and Molecular Neuroscience

Cite this

Grover, D., Verma, R., Goes, F. S., Belmonte Mahon, P. L., Gershon, E. S., McMahon, F. J., ... Murphy, D. L. (2009). Family-based association of YWHAH in psychotic bipolar disorder. American Journal of Medical Genetics, Part B: Neuropsychiatric Genetics, 150(7), 977-983. https://doi.org/10.1002/ajmg.b.30927

Family-based association of YWHAH in psychotic bipolar disorder. / Grover, Deepak; Verma, Ranjana; Goes, Fernando S.; Belmonte Mahon, Pamela L.; Gershon, Elliot S.; McMahon, Francis J.; Potash, James B.; McMahon, F. J.; Steele, J.; Pearl, J.; Kassem, L.; Lopez, V.; Schulze, T.; Potash, J.; MacKinnon, D.; Miller, E.; Toolan, J.; Zandi, P.; Simpson, S.; Nurnberger, John; Miller, M.; Bowman, E.; Reich, T.; Goate, A.; Rice, J.; DePaulo, J. R.; Simpson, S.; Stine, C.; Gershon, E.; Kazuba, D.; Maxwell, E.; Nurnberger, J.; Miller, M. J.; Bowman, E. S.; Rau, N. L.; Moe, P. R.; Samavedy, N.; El-Mallakh, R.; Manji, H.; Glitz, D. A.; Meyer, E. T.; Smiley, C.; Foroud, Tatiana; Flury, L.; Dick, D. M.; Edenberg, Howard; Rice, J.; Reich, T.; Goate, A.; Bierut, L.; McInnis, M.; DePaulo, J. R.; MacKinnon, D. F.; Mondimore, F. M.; Potash, J. B.; Zandi, P. P.; Avramopoulos, D.; Payne, J.; Berrettini, W.; Byerley, W.; Vawter, M.; Coryell, W.; Crowe, R.; Gershon, E.; Badner, J.; McMahon, F.; Liu, C.; Sanders, A.; Caserta, M.; Dinwiddie, S.; Nguyen, T.; Harakal, D.; Kelsoe, J.; McKinney, R.; Scheftner, W.; Kravitz, H. M.; Marta, D.; Vaughn-Brown, A.; Bederow, L.; McMahon, F.; Kassem, L.; Detera-Wadleigh, S.; Austin, L.; Murphy, D. L.

In: American Journal of Medical Genetics, Part B: Neuropsychiatric Genetics, Vol. 150, No. 7, 05.10.2009, p. 977-983.

Research output: Contribution to journalArticle

Grover, D, Verma, R, Goes, FS, Belmonte Mahon, PL, Gershon, ES, McMahon, FJ, Potash, JB, McMahon, FJ, Steele, J, Pearl, J, Kassem, L, Lopez, V, Schulze, T, Potash, J, MacKinnon, D, Miller, E, Toolan, J, Zandi, P, Simpson, S, Nurnberger, J, Miller, M, Bowman, E, Reich, T, Goate, A, Rice, J, DePaulo, JR, Simpson, S, Stine, C, Gershon, E, Kazuba, D, Maxwell, E, Nurnberger, J, Miller, MJ, Bowman, ES, Rau, NL, Moe, PR, Samavedy, N, El-Mallakh, R, Manji, H, Glitz, DA, Meyer, ET, Smiley, C, Foroud, T, Flury, L, Dick, DM, Edenberg, H, Rice, J, Reich, T, Goate, A, Bierut, L, McInnis, M, DePaulo, JR, MacKinnon, DF, Mondimore, FM, Potash, JB, Zandi, PP, Avramopoulos, D, Payne, J, Berrettini, W, Byerley, W, Vawter, M, Coryell, W, Crowe, R, Gershon, E, Badner, J, McMahon, F, Liu, C, Sanders, A, Caserta, M, Dinwiddie, S, Nguyen, T, Harakal, D, Kelsoe, J, McKinney, R, Scheftner, W, Kravitz, HM, Marta, D, Vaughn-Brown, A, Bederow, L, McMahon, F, Kassem, L, Detera-Wadleigh, S, Austin, L & Murphy, DL 2009, 'Family-based association of YWHAH in psychotic bipolar disorder', American Journal of Medical Genetics, Part B: Neuropsychiatric Genetics, vol. 150, no. 7, pp. 977-983. https://doi.org/10.1002/ajmg.b.30927
Grover, Deepak ; Verma, Ranjana ; Goes, Fernando S. ; Belmonte Mahon, Pamela L. ; Gershon, Elliot S. ; McMahon, Francis J. ; Potash, James B. ; McMahon, F. J. ; Steele, J. ; Pearl, J. ; Kassem, L. ; Lopez, V. ; Schulze, T. ; Potash, J. ; MacKinnon, D. ; Miller, E. ; Toolan, J. ; Zandi, P. ; Simpson, S. ; Nurnberger, John ; Miller, M. ; Bowman, E. ; Reich, T. ; Goate, A. ; Rice, J. ; DePaulo, J. R. ; Simpson, S. ; Stine, C. ; Gershon, E. ; Kazuba, D. ; Maxwell, E. ; Nurnberger, J. ; Miller, M. J. ; Bowman, E. S. ; Rau, N. L. ; Moe, P. R. ; Samavedy, N. ; El-Mallakh, R. ; Manji, H. ; Glitz, D. A. ; Meyer, E. T. ; Smiley, C. ; Foroud, Tatiana ; Flury, L. ; Dick, D. M. ; Edenberg, Howard ; Rice, J. ; Reich, T. ; Goate, A. ; Bierut, L. ; McInnis, M. ; DePaulo, J. R. ; MacKinnon, D. F. ; Mondimore, F. M. ; Potash, J. B. ; Zandi, P. P. ; Avramopoulos, D. ; Payne, J. ; Berrettini, W. ; Byerley, W. ; Vawter, M. ; Coryell, W. ; Crowe, R. ; Gershon, E. ; Badner, J. ; McMahon, F. ; Liu, C. ; Sanders, A. ; Caserta, M. ; Dinwiddie, S. ; Nguyen, T. ; Harakal, D. ; Kelsoe, J. ; McKinney, R. ; Scheftner, W. ; Kravitz, H. M. ; Marta, D. ; Vaughn-Brown, A. ; Bederow, L. ; McMahon, F. ; Kassem, L. ; Detera-Wadleigh, S. ; Austin, L. ; Murphy, D. L. / Family-based association of YWHAH in psychotic bipolar disorder. In: American Journal of Medical Genetics, Part B: Neuropsychiatric Genetics. 2009 ; Vol. 150, No. 7. pp. 977-983.
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abstract = "YWHAH is a positional and functional candidate gene for both schizophrenia and bipolar disorder (BP). This gene has been previously shown to be associated with both disorders, and the chromosome location (22q12.3) has been repeatedly implicated in linkage studies for these disorders. It codes for thehsubtype of the 14-3-3 protein family, is expressed mainly in brain, and is involved in HPA axis regulation.Weinvestigated the association ofYWHAHwith BP in a large sample, consisting of 1211 subjects from 318 nuclear families including 554 affected offspring. We tested for association with the standard BP phenotype as well as subtypes defined by psychotic and mood-incongruent features. We genotyped five tag SNPs and the (GCCTGCA)n polymorphic locus present in this gene. Using a family-based association test, we found that rs2246704 was associated with BP (OR 1.31, P=0.03) and psychotic BP (OR=1.66, P=0.002). The polymorphic repeat and two other SNPs were also modestly associated with psychotic BP. We have provided additional evidence for association of variants in YWHAH with major mental illness. Additional association analyses of larger sample sets will be required to clarify the role of YWHAH in schizophrenia and BP. The use of clinical sub-phenotypes such as psychotic features or other potential schizophrenia/BP overlap variables including cognitive abnormalities and poor functioning might shed further light on the potential subtypes of illness most closely associated with genetic variation in YWHAH.",
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TY - JOUR

T1 - Family-based association of YWHAH in psychotic bipolar disorder

AU - Grover, Deepak

AU - Verma, Ranjana

AU - Goes, Fernando S.

AU - Belmonte Mahon, Pamela L.

AU - Gershon, Elliot S.

AU - McMahon, Francis J.

AU - Potash, James B.

AU - McMahon, F. J.

AU - Steele, J.

AU - Pearl, J.

AU - Kassem, L.

AU - Lopez, V.

AU - Schulze, T.

AU - Potash, J.

AU - MacKinnon, D.

AU - Miller, E.

AU - Toolan, J.

AU - Zandi, P.

AU - Simpson, S.

AU - Nurnberger, John

AU - Miller, M.

AU - Bowman, E.

AU - Reich, T.

AU - Goate, A.

AU - Rice, J.

AU - DePaulo, J. R.

AU - Simpson, S.

AU - Stine, C.

AU - Gershon, E.

AU - Kazuba, D.

AU - Maxwell, E.

AU - Nurnberger, J.

AU - Miller, M. J.

AU - Bowman, E. S.

AU - Rau, N. L.

AU - Moe, P. R.

AU - Samavedy, N.

AU - El-Mallakh, R.

AU - Manji, H.

AU - Glitz, D. A.

AU - Meyer, E. T.

AU - Smiley, C.

AU - Foroud, Tatiana

AU - Flury, L.

AU - Dick, D. M.

AU - Edenberg, Howard

AU - Rice, J.

AU - Reich, T.

AU - Goate, A.

AU - Bierut, L.

AU - McInnis, M.

AU - DePaulo, J. R.

AU - MacKinnon, D. F.

AU - Mondimore, F. M.

AU - Potash, J. B.

AU - Zandi, P. P.

AU - Avramopoulos, D.

AU - Payne, J.

AU - Berrettini, W.

AU - Byerley, W.

AU - Vawter, M.

AU - Coryell, W.

AU - Crowe, R.

AU - Gershon, E.

AU - Badner, J.

AU - McMahon, F.

AU - Liu, C.

AU - Sanders, A.

AU - Caserta, M.

AU - Dinwiddie, S.

AU - Nguyen, T.

AU - Harakal, D.

AU - Kelsoe, J.

AU - McKinney, R.

AU - Scheftner, W.

AU - Kravitz, H. M.

AU - Marta, D.

AU - Vaughn-Brown, A.

AU - Bederow, L.

AU - McMahon, F.

AU - Kassem, L.

AU - Detera-Wadleigh, S.

AU - Austin, L.

AU - Murphy, D. L.

PY - 2009/10/5

Y1 - 2009/10/5

N2 - YWHAH is a positional and functional candidate gene for both schizophrenia and bipolar disorder (BP). This gene has been previously shown to be associated with both disorders, and the chromosome location (22q12.3) has been repeatedly implicated in linkage studies for these disorders. It codes for thehsubtype of the 14-3-3 protein family, is expressed mainly in brain, and is involved in HPA axis regulation.Weinvestigated the association ofYWHAHwith BP in a large sample, consisting of 1211 subjects from 318 nuclear families including 554 affected offspring. We tested for association with the standard BP phenotype as well as subtypes defined by psychotic and mood-incongruent features. We genotyped five tag SNPs and the (GCCTGCA)n polymorphic locus present in this gene. Using a family-based association test, we found that rs2246704 was associated with BP (OR 1.31, P=0.03) and psychotic BP (OR=1.66, P=0.002). The polymorphic repeat and two other SNPs were also modestly associated with psychotic BP. We have provided additional evidence for association of variants in YWHAH with major mental illness. Additional association analyses of larger sample sets will be required to clarify the role of YWHAH in schizophrenia and BP. The use of clinical sub-phenotypes such as psychotic features or other potential schizophrenia/BP overlap variables including cognitive abnormalities and poor functioning might shed further light on the potential subtypes of illness most closely associated with genetic variation in YWHAH.

AB - YWHAH is a positional and functional candidate gene for both schizophrenia and bipolar disorder (BP). This gene has been previously shown to be associated with both disorders, and the chromosome location (22q12.3) has been repeatedly implicated in linkage studies for these disorders. It codes for thehsubtype of the 14-3-3 protein family, is expressed mainly in brain, and is involved in HPA axis regulation.Weinvestigated the association ofYWHAHwith BP in a large sample, consisting of 1211 subjects from 318 nuclear families including 554 affected offspring. We tested for association with the standard BP phenotype as well as subtypes defined by psychotic and mood-incongruent features. We genotyped five tag SNPs and the (GCCTGCA)n polymorphic locus present in this gene. Using a family-based association test, we found that rs2246704 was associated with BP (OR 1.31, P=0.03) and psychotic BP (OR=1.66, P=0.002). The polymorphic repeat and two other SNPs were also modestly associated with psychotic BP. We have provided additional evidence for association of variants in YWHAH with major mental illness. Additional association analyses of larger sample sets will be required to clarify the role of YWHAH in schizophrenia and BP. The use of clinical sub-phenotypes such as psychotic features or other potential schizophrenia/BP overlap variables including cognitive abnormalities and poor functioning might shed further light on the potential subtypes of illness most closely associated with genetic variation in YWHAH.

KW - 14-3-3

KW - Bipolar disorder

KW - Psychosis

KW - Schizophrenia

KW - YWHAH

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DO - 10.1002/ajmg.b.30927

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JF - American Journal of Medical Genetics, Part B: Neuropsychiatric Genetics

SN - 1552-4841

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