Loci on chromosomes 6q and 6p interact to increase susceptibility to bipolar affective disorder in the national institute of mental health genetics initiative pedigrees

Thomas G. Schulze; Silvia Buervenich; Judith A. Badner; C. J.M. Steele; Sevilla D. Detera-Wadleigh; Danielle Dick; Tatiana Foroud; Nancy J. Cox; Dean F. MacKinnon; James B. Potash; Wade H. Berrettini; William Byerley; William Coryell; J. Raymond DePaulo; Elliot S. Gershon; John R. Kelsoe; Melvin G. McInnis; Dennis L. Murphy; Theodore Reich; William Scheftner; John I. Nurnberger; Francis J. McMahon

doi:10.1016/j.biopsych.2004.04.004

Loci on chromosomes 6q and 6p interact to increase susceptibility to bipolar affective disorder in the national institute of mental health genetics initiative pedigrees

Thomas G. Schulze, Silvia Buervenich, Judith A. Badner, C. J.M. Steele, Sevilla D. Detera-Wadleigh, Danielle Dick, Tatiana Foroud, Nancy J. Cox, Dean F. MacKinnon, James B. Potash, Wade H. Berrettini, William Byerley, William Coryell, J. Raymond DePaulo, Elliot S. Gershon, John R. Kelsoe, Melvin G. McInnis, Dennis L. Murphy, Theodore Reich, William ScheftnerJohn I. Nurnberger, Francis J. McMahon

School of Medicine

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

Abstract

Background We have reported genetic linkage between bipolar disorder and markers on chromosome 6q16.3-22.1 in the National Institute of Mental Health Genetics Initiative wave 3 pedigrees. Here we test for: 1) robustness of the linkage to differing analysis methods, genotyping error, and gender-specific maps; 2) parent-of-origin effects; and 3) interaction with markers within the schizophrenia linkage region on chromosome 6p. Methods Members of 245 families ascertained through a sibling pair affected with bipolar I or schizoaffective-bipolar disorder were genotyped with 18 markers spanning chromosome 6. Nonparametric linkage analysis was performed. Results Linkage to 6q is robust to analysis method, gender-specific map differences, and genotyping error. The locus confers a 1.4-fold increased risk. Affected siblings share the maternal more often than the paternal chromosome (p = .006), which could reflect a maternal parent-of-origin effect. There is a positive correlation between family-specific linkage scores on 6q and those on 6p22.2 (r = .26; p < .0001). Linkage analysis for each locus conditioned on evidence of linkage to the other increases the evidence for linkage at both loci (p < .0005). Logarithm of the odds (LOD) scores increased from 2.26 to 5.42 on 6q and from .35 to 2.26 on 6p22.2. Conclusions These results support linkage of bipolar disorder to 6q, uncover a maternal parent-of-origin effect, and demonstrate an interaction of this locus with one on chromosome 6p22.2, previously linked only to schizophrenia.

Original language	English (US)
Pages (from-to)	18-23
Number of pages	6
Journal	Biological psychiatry
Volume	56
Issue number	1
DOIs	https://doi.org/10.1016/j.biopsych.2004.04.004
State	Published - Jul 1 2004

Keywords

Epistasis
GRIK2
LOD score
manic-depressive illness
nonparametric linkage analysis
prolyl endopeptidase

ASJC Scopus subject areas

Biological Psychiatry

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Schulze, T. G., Buervenich, S., Badner, J. A., Steele, C. J. M., Detera-Wadleigh, S. D., Dick, D., Foroud, T., Cox, N. J., MacKinnon, D. F., Potash, J. B., Berrettini, W. H., Byerley, W., Coryell, W., DePaulo, J. R., Gershon, E. S., Kelsoe, J. R., McInnis, M. G., Murphy, D. L., Reich, T., ... McMahon, F. J. (2004). Loci on chromosomes 6q and 6p interact to increase susceptibility to bipolar affective disorder in the national institute of mental health genetics initiative pedigrees. Biological psychiatry, 56(1), 18-23. https://doi.org/10.1016/j.biopsych.2004.04.004

Loci on chromosomes 6q and 6p interact to increase susceptibility to bipolar affective disorder in the national institute of mental health genetics initiative pedigrees. / Schulze, Thomas G.; Buervenich, Silvia; Badner, Judith A.; Steele, C. J.M.; Detera-Wadleigh, Sevilla D.; Dick, Danielle; Foroud, Tatiana; Cox, Nancy J.; MacKinnon, Dean F.; Potash, James B.; Berrettini, Wade H.; Byerley, William; Coryell, William; DePaulo, J. Raymond; Gershon, Elliot S.; Kelsoe, John R.; McInnis, Melvin G.; Murphy, Dennis L.; Reich, Theodore; Scheftner, William; Nurnberger, John I.; McMahon, Francis J.

In: Biological psychiatry, Vol. 56, No. 1, 01.07.2004, p. 18-23.

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

Schulze, TG, Buervenich, S, Badner, JA, Steele, CJM, Detera-Wadleigh, SD, Dick, D, Foroud, T, Cox, NJ, MacKinnon, DF, Potash, JB, Berrettini, WH, Byerley, W, Coryell, W, DePaulo, JR, Gershon, ES, Kelsoe, JR, McInnis, MG, Murphy, DL, Reich, T, Scheftner, W, Nurnberger, JI & McMahon, FJ 2004, 'Loci on chromosomes 6q and 6p interact to increase susceptibility to bipolar affective disorder in the national institute of mental health genetics initiative pedigrees', Biological psychiatry, vol. 56, no. 1, pp. 18-23. https://doi.org/10.1016/j.biopsych.2004.04.004

Schulze, Thomas G. ; Buervenich, Silvia ; Badner, Judith A. ; Steele, C. J.M. ; Detera-Wadleigh, Sevilla D. ; Dick, Danielle ; Foroud, Tatiana ; Cox, Nancy J. ; MacKinnon, Dean F. ; Potash, James B. ; Berrettini, Wade H. ; Byerley, William ; Coryell, William ; DePaulo, J. Raymond ; Gershon, Elliot S. ; Kelsoe, John R. ; McInnis, Melvin G. ; Murphy, Dennis L. ; Reich, Theodore ; Scheftner, William ; Nurnberger, John I. ; McMahon, Francis J. / Loci on chromosomes 6q and 6p interact to increase susceptibility to bipolar affective disorder in the national institute of mental health genetics initiative pedigrees. In: Biological psychiatry. 2004 ; Vol. 56, No. 1. pp. 18-23.

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title = "Loci on chromosomes 6q and 6p interact to increase susceptibility to bipolar affective disorder in the national institute of mental health genetics initiative pedigrees",

abstract = "Background We have reported genetic linkage between bipolar disorder and markers on chromosome 6q16.3-22.1 in the National Institute of Mental Health Genetics Initiative wave 3 pedigrees. Here we test for: 1) robustness of the linkage to differing analysis methods, genotyping error, and gender-specific maps; 2) parent-of-origin effects; and 3) interaction with markers within the schizophrenia linkage region on chromosome 6p. Methods Members of 245 families ascertained through a sibling pair affected with bipolar I or schizoaffective-bipolar disorder were genotyped with 18 markers spanning chromosome 6. Nonparametric linkage analysis was performed. Results Linkage to 6q is robust to analysis method, gender-specific map differences, and genotyping error. The locus confers a 1.4-fold increased risk. Affected siblings share the maternal more often than the paternal chromosome (p = .006), which could reflect a maternal parent-of-origin effect. There is a positive correlation between family-specific linkage scores on 6q and those on 6p22.2 (r = .26; p < .0001). Linkage analysis for each locus conditioned on evidence of linkage to the other increases the evidence for linkage at both loci (p < .0005). Logarithm of the odds (LOD) scores increased from 2.26 to 5.42 on 6q and from .35 to 2.26 on 6p22.2. Conclusions These results support linkage of bipolar disorder to 6q, uncover a maternal parent-of-origin effect, and demonstrate an interaction of this locus with one on chromosome 6p22.2, previously linked only to schizophrenia.",

keywords = "Epistasis, GRIK2, LOD score, manic-depressive illness, nonparametric linkage analysis, prolyl endopeptidase",

author = "Schulze, {Thomas G.} and Silvia Buervenich and Badner, {Judith A.} and Steele, {C. J.M.} and Detera-Wadleigh, {Sevilla D.} and Danielle Dick and Tatiana Foroud and Cox, {Nancy J.} and MacKinnon, {Dean F.} and Potash, {James B.} and Berrettini, {Wade H.} and William Byerley and William Coryell and DePaulo, {J. Raymond} and Gershon, {Elliot S.} and Kelsoe, {John R.} and McInnis, {Melvin G.} and Murphy, {Dennis L.} and Theodore Reich and William Scheftner and Nurnberger, {John I.} and McMahon, {Francis J.}",

note = "Funding Information: This research was supported by grants from the National Institute of Mental Health (NIMH); the Edward F. Mallinckrodt, Jr. Foundation (FJM); the Chicago Brain Research Institute (FJM); and the National Alliance for Research in Schizophrenia and Depression (TGS, FJM). This work was also supported by the NIMH Intramural Research Program (TGS, SB, CJMT, SDW, FJM). Funding Information: Genotyping services were provided by the Center for Inherited Disease Research (CIDR). CIDR is fully funded through a federal contract from the National Institutes of Health to The Johns Hopkins University, contract N01-HG-65403. We thank Jay Tischfield, Ph.D. (Rutgers University Cell and DNA Repository) for transforming cell lines and providing DNA samples. ",

year = "2004",

month = jul,

day = "1",

doi = "10.1016/j.biopsych.2004.04.004",

language = "English (US)",

volume = "56",

pages = "18--23",

journal = "Biological Psychiatry",

issn = "0006-3223",

publisher = "Elsevier USA",

number = "1",

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TY - JOUR

T1 - Loci on chromosomes 6q and 6p interact to increase susceptibility to bipolar affective disorder in the national institute of mental health genetics initiative pedigrees

AU - Schulze, Thomas G.

AU - Buervenich, Silvia

AU - Badner, Judith A.

AU - Steele, C. J.M.

AU - Detera-Wadleigh, Sevilla D.

AU - Dick, Danielle

AU - Foroud, Tatiana

AU - Cox, Nancy J.

AU - MacKinnon, Dean F.

AU - Potash, James B.

AU - Berrettini, Wade H.

AU - Byerley, William

AU - Coryell, William

AU - DePaulo, J. Raymond

AU - Gershon, Elliot S.

AU - Kelsoe, John R.

AU - McInnis, Melvin G.

AU - Murphy, Dennis L.

AU - Reich, Theodore

AU - Scheftner, William

AU - Nurnberger, John I.

AU - McMahon, Francis J.

N1 - Funding Information: This research was supported by grants from the National Institute of Mental Health (NIMH); the Edward F. Mallinckrodt, Jr. Foundation (FJM); the Chicago Brain Research Institute (FJM); and the National Alliance for Research in Schizophrenia and Depression (TGS, FJM). This work was also supported by the NIMH Intramural Research Program (TGS, SB, CJMT, SDW, FJM). Funding Information: Genotyping services were provided by the Center for Inherited Disease Research (CIDR). CIDR is fully funded through a federal contract from the National Institutes of Health to The Johns Hopkins University, contract N01-HG-65403. We thank Jay Tischfield, Ph.D. (Rutgers University Cell and DNA Repository) for transforming cell lines and providing DNA samples.

PY - 2004/7/1

Y1 - 2004/7/1

N2 - Background We have reported genetic linkage between bipolar disorder and markers on chromosome 6q16.3-22.1 in the National Institute of Mental Health Genetics Initiative wave 3 pedigrees. Here we test for: 1) robustness of the linkage to differing analysis methods, genotyping error, and gender-specific maps; 2) parent-of-origin effects; and 3) interaction with markers within the schizophrenia linkage region on chromosome 6p. Methods Members of 245 families ascertained through a sibling pair affected with bipolar I or schizoaffective-bipolar disorder were genotyped with 18 markers spanning chromosome 6. Nonparametric linkage analysis was performed. Results Linkage to 6q is robust to analysis method, gender-specific map differences, and genotyping error. The locus confers a 1.4-fold increased risk. Affected siblings share the maternal more often than the paternal chromosome (p = .006), which could reflect a maternal parent-of-origin effect. There is a positive correlation between family-specific linkage scores on 6q and those on 6p22.2 (r = .26; p < .0001). Linkage analysis for each locus conditioned on evidence of linkage to the other increases the evidence for linkage at both loci (p < .0005). Logarithm of the odds (LOD) scores increased from 2.26 to 5.42 on 6q and from .35 to 2.26 on 6p22.2. Conclusions These results support linkage of bipolar disorder to 6q, uncover a maternal parent-of-origin effect, and demonstrate an interaction of this locus with one on chromosome 6p22.2, previously linked only to schizophrenia.

AB - Background We have reported genetic linkage between bipolar disorder and markers on chromosome 6q16.3-22.1 in the National Institute of Mental Health Genetics Initiative wave 3 pedigrees. Here we test for: 1) robustness of the linkage to differing analysis methods, genotyping error, and gender-specific maps; 2) parent-of-origin effects; and 3) interaction with markers within the schizophrenia linkage region on chromosome 6p. Methods Members of 245 families ascertained through a sibling pair affected with bipolar I or schizoaffective-bipolar disorder were genotyped with 18 markers spanning chromosome 6. Nonparametric linkage analysis was performed. Results Linkage to 6q is robust to analysis method, gender-specific map differences, and genotyping error. The locus confers a 1.4-fold increased risk. Affected siblings share the maternal more often than the paternal chromosome (p = .006), which could reflect a maternal parent-of-origin effect. There is a positive correlation between family-specific linkage scores on 6q and those on 6p22.2 (r = .26; p < .0001). Linkage analysis for each locus conditioned on evidence of linkage to the other increases the evidence for linkage at both loci (p < .0005). Logarithm of the odds (LOD) scores increased from 2.26 to 5.42 on 6q and from .35 to 2.26 on 6p22.2. Conclusions These results support linkage of bipolar disorder to 6q, uncover a maternal parent-of-origin effect, and demonstrate an interaction of this locus with one on chromosome 6p22.2, previously linked only to schizophrenia.

KW - Epistasis

KW - GRIK2

KW - LOD score

KW - manic-depressive illness

KW - nonparametric linkage analysis

KW - prolyl endopeptidase

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U2 - 10.1016/j.biopsych.2004.04.004

DO - 10.1016/j.biopsych.2004.04.004

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C2 - 15219468

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JO - Biological Psychiatry

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