Loci on chromosomes 6q and 6p interact to increase susceptibility to bipolar affective disorder in the National Institute of Mental Health Genetics Initiative pedigrees

被引:60
作者
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
机构
[1] Cent Inst Mental Hlth, Div Genet Epidemiol Psychiat, D-68159 Mannheim, Germany
[2] NIMH, Mood & Anxiety Program, Bethesda, MD 20892 USA
[3] NIMH, Clin Sci Lab, Bethesda, MD 20892 USA
[4] Johns Hopkins Univ, Dept Psychiat, Baltimore, MD 21218 USA
[5] Rush Univ, Dept Psychiat, Chicago, IL 60612 USA
[6] Univ Chicago, Dept Psychiat, Chicago, IL 60637 USA
[7] Univ Chicago, Dept Human Genet, Chicago, IL 60637 USA
[8] Indiana Univ, Sch Med, Dept Med & Mol Genet, Indianapolis, IN 46204 USA
[9] Indiana Univ, Sch Med, Dept Psychiat, Indianapolis, IN 46204 USA
[10] Univ Calif Irvine, Irvine, CA USA
[11] Univ Penn, Philadelphia, PA 19104 USA
[12] Univ Iowa, Iowa City, IA USA
[13] Univ Calif San Diego, San Diego, CA 92103 USA
[14] Washington Univ, Dept Psychiat, St Louis, MO USA
基金
美国国家卫生研究院;
关键词
epistasis; GRIK2; LOD score; manic-depressive illness; nonparametric linkage analysis; prolyl endopeptidase;
D O I
10.1016/j.biopsych.2004.04.004
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
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 6-p22.2 (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.
引用
收藏
页码:18 / 23
页数:6
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