Linkage of bipolar disorder to chromosome 18q and the validity of bipolar II disorder

被引:81
作者
McMahon, FJ
Simpson, SG
McInnis, MG
Badner, JA
MacKinnon, DF
DePaulo, JR
机构
[1] Univ Chicago, Dept Psychiat, Chicago, IL 60637 USA
[2] Johns Hopkins Univ, Sch Med, Baltimore, MD 21205 USA
关键词
D O I
10.1001/archpsyc.58.11.1025
中图分类号
R749 [精神病学];
学科分类号
100205 ;
摘要
Background: An analysis of the relationship between clinical features and allele sharing could clarify the issue of genetic linkage between bipolar affective disorder (BPAD) and chromosome 18q, contributing to the definition of genetically valid clinical subtypes. Methods: Relatives ascertained through a proband who had bipolar I disorder (BPI) were interviewed by a psychiatrist, assigned an all-sources diagnosis, and genotyped with 32 markers on 18q21-23. Exploratory findings from the first 28 families (n = 247) were tested prospectively in an additional 30 families (n = 259), and the effect of confirmed findings on the linkage evidence was assessed. Results: In exploratory analyses, paternal allele sharing on 18q21 was significantly (P=.03)associated with a diagnostic subtype, and was greatest in pairs where both siblings had bipolar II disorder (BPII). Prospective analysis confirmed the finding that BPII-BPII sibling pairs showed significantly (P=.016) greater paternal allele sharing. Paternal allele sharing across 18q21-23 was also significantly greater in families with at least one BPII-BPII sibling pair. In these families, multipoint affected sibling-pair linkage analysis produced a peak paternal lod score of 4.67 (1-lod confidence interval, 12 centimorgans [cM]) vs 1.53 (1-lod confidence interval, 44 cM) in all families. Conclusions: Affected sibling pairs with BPII discriminated between families who showed evidence of linkage to 18q, and families who did not. Families with a BPII sibling pair produced an increased lod score and improved linkage resolution, These findings, limited by the small number of BPII-BPII sibling pairs, strengthen the evidence of genetic linkage between BPAD and chromosome 18q, and provide preliminary support for BPII as a genetically valid subtype of BPAD.
引用
收藏
页码:1025 / 1031
页数:7
相关论文
共 38 条
  • [21] GENETIC DISSECTION OF COMPLEX TRAITS - GUIDELINES FOR INTERPRETING AND REPORTING LINKAGE RESULTS
    LANDER, E
    KRUGLYAK, L
    [J]. NATURE GENETICS, 1995, 11 (03) : 241 - 247
  • [22] Effects of stratification in the analysis of affected-sib-pair data: Benefits and costs
    Leal, SM
    Ott, J
    [J]. AMERICAN JOURNAL OF HUMAN GENETICS, 2000, 66 (02) : 567 - 575
  • [23] MacKinnon DF, 1998, AM J PSYCHIAT, V155, P829
  • [24] Linkage analysis between pericentromeric markers on chromosome 18 and bipolar disorder: A replication test
    Maier, W
    Hallmayer, J
    Zill, P
    Bondy, B
    Lichtermann, D
    Ackenheil, M
    Minges, J
    Wildenauer, D
    [J]. PSYCHIATRY RESEARCH, 1995, 59 (1-2) : 7 - 15
  • [25] Linkage of bipolar affective disorder to chromosome 18 markers in a new pedigree series
    McMahon, FJ
    Hopkins, PJ
    Xu, JF
    McInnis, MG
    Shaw, S
    Cardon, L
    Simpson, SG
    MacKinnon, DF
    Stine, OC
    Sherrington, R
    Meyers, DA
    DePaulo, JR
    [J]. AMERICAN JOURNAL OF HUMAN GENETICS, 1997, 61 (06) : 1397 - 1404
  • [26] McMahon FJ, 1998, AM J MED GENET, V81, P248
  • [27] A catalogue of imprinted genes and parent-of-origin effects in humans and animals
    Morison, IM
    Reeve, AE
    [J]. HUMAN MOLECULAR GENETICS, 1998, 7 (10) : 1599 - 1609
  • [28] Evaluation of linkage of bipolar affective disorder to chromosome 18 in a sample of 57 German families
    Nothen, MM
    Cichon, S
    Rohleder, H
    Hemmer, S
    Franzek, E
    Fritze, J
    Albus, M
    Borrmann-Hassenbach, M
    Kreiner, R
    Weigelt, B
    Minges, J
    Lichtermann, D
    Maier, W
    Craddock, N
    Fimmers, R
    Holler, T
    Baur, MP
    Rietschel, M
    Propping, P
    [J]. MOLECULAR PSYCHIATRY, 1999, 4 (01) : 76 - 84
  • [29] GENETIC-LINKAGE STUDIES OF BIPOLAR DISORDER
    REICH, T
    [J]. CURRENT OPINION IN PSYCHIATRY, 1995, 8 (01) : 3 - 6
  • [30] Understanding the genetic basis of mood disorders: Where do we stand?
    Reus, VI
    Freimer, NB
    [J]. AMERICAN JOURNAL OF HUMAN GENETICS, 1997, 60 (06) : 1283 - 1288