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 Bennett 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 & 2 others John I. Nurnberger, Francis J. McMahon

Research output: Contribution to journalArticle

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 languageEnglish (US)
Pages (from-to)18-23
Number of pages6
JournalBiological Psychiatry
Volume56
Issue number1
DOIs
StatePublished - Jul 1 2004

Fingerprint

National Institute of Mental Health (U.S.)
Pedigree
Mood Disorders
Bipolar Disorder
Chromosomes
Mothers
Siblings
Schizophrenia
Chromosomes, Human, Pair 6
Genetic Linkage
Genetic Markers
Psychotic Disorders

Keywords

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

ASJC Scopus subject areas

  • Biological Psychiatry

Cite this

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 Bennett; 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 journalArticle

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 Bennett ; 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.
@article{722d3c1ca38d48718ac1787efdc8aae9,
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 Bennett} 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.}",
year = "2004",
month = "7",
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",

}

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 Bennett

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.

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

UR - http://www.scopus.com/inward/record.url?scp=3042567235&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=3042567235&partnerID=8YFLogxK

U2 - 10.1016/j.biopsych.2004.04.004

DO - 10.1016/j.biopsych.2004.04.004

M3 - Article

VL - 56

SP - 18

EP - 23

JO - Biological Psychiatry

JF - Biological Psychiatry

SN - 0006-3223

IS - 1

ER -