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

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

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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, …

Biological psychiatry (1969), Vol.56(1), pp.18-23

2004

DOI: 10.1016/j.biopsych.2004.04.004

PMID: 15219468

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Abstract

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. 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. 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. 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.

LOD score

manic-depressive illness

Epistasis

GRIK2

nonparametric linkage analysis

prolyl endopeptidase

Details

Title: Subtitle: Loci on chromosomes 6q and 6p interact to increase susceptibility to bipolar affective disorder in the national institute of mental health genetics initiative pedigrees
Creators: Thomas G Schulze - Division of Genetic Epidemiology in Psychiatry (TGS), Central Institute of Mental Health, Mannheim, Germany
Silvia Buervenich - Genetic Basis of Mood and Anxiety Disorders (TGS, SB, CJMS, SDD-W, FJM), Mood and Anxiety Program, BethesdaUSA
Judith A Badner - Laboratory of Clinical Science (DLM), National Institute of Mental Health, Bethesda;, USA
C.J.M Steele - Genetic Basis of Mood and Anxiety Disorders (TGS, SB, CJMS, SDD-W, FJM), Mood and Anxiety Program, BethesdaUSA
Sevilla D Detera-Wadleigh - Genetic Basis of Mood and Anxiety Disorders (TGS, SB, CJMS, SDD-W, FJM), Mood and Anxiety Program, BethesdaUSA
Danielle Dick - Departments of Psychiatry (JAB, ESG, FJM), Chicago, USA
Tatiana Foroud - Departments of Psychiatry (JAB, ESG, FJM), Chicago, USA
Nancy J Cox - Medical and Molecular Genetics (DD, TF, JIN), Indianapolis, USA
Dean F MacKinnon - Psychiatry (TF, JIN), Indiana University School of Medicine, Indianapolis, Indiana, USA
James B Potash - Psychiatry (TF, JIN), Indiana University School of Medicine, Indianapolis, Indiana, USA
Wade H Berrettini - Department of Psychiatry (DFM, JBP, JRD, MGM), The Johns Hopkins University, Baltimore, Maryland, USA
William Byerley - University of Pennsylvania (WHB), Philadelphia, Pennsylvania, USA
William Coryell - University of California (WB), Irvine, California, USA
J.Raymond DePaulo - Psychiatry (TF, JIN), Indiana University School of Medicine, Indianapolis, Indiana, USA
Elliot S Gershon - Laboratory of Clinical Science (DLM), National Institute of Mental Health, Bethesda;, USA
John R Kelsoe - University of Iowa (WC), Iowa City, Iowa, USA
Melvin G McInnis - Psychiatry (TF, JIN), Indiana University School of Medicine, Indianapolis, Indiana, USA
Dennis L Murphy - University of California (JRK), San Diego, California, USA
Theodore Reich - Department of Psychiatry (TR), Washington University, St. Louis, Missouri, USA
William Scheftner - Rush University Department of Psychiatry (WS), Chicago, Illinois, USA
John I Nurnberger - Laboratory of Clinical Science (DLM), National Institute of Mental Health, Bethesda;, USA
Francis J McMahon - Laboratory of Clinical Science (DLM), National Institute of Mental Health, Bethesda;, USA
Resource Type: Journal article
Publication Details: Biological psychiatry (1969), Vol.56(1), pp.18-23
Publisher: Elsevier Inc
DOI: 10.1016/j.biopsych.2004.04.004
PMID: 15219468
ISSN: 0006-3223
eISSN: 1873-2402
Language: English
Date published: 2004
Academic Unit: Psychiatry
Record Identifier: 9984003423502771

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