Home LiteratureArticle Details
PMID: 10318931 Published · ppublish English Journal Article

A high-density genome scan detects evidence for a bipolar-disorder susceptibility locus on 13q32 and other potential loci on 1q32 and 18p11.2.

Proceedings of the National Academy of Sciences of the United States of America ·Vol. 96 ·No. 10 ·1999-05-11 ·Pages 5604-9

Detera-Wadleigh SD, Badner JA, Berrettini WH, Yoshikawa T, Goldin LR, Turner G, Rollins DY, Moses T, Sanders AR, Karkera JD, Esterling LE, Zeng J, Ferraro TN, Guroff JJ, Kazuba D, Maxwell ME, Nurnberger JI, Gershon ES

Abstract

Bipolar disorder is a severe mental illness characterized by mood swings of elation and depression. Family, twin, and adoption studies suggest a complex genetic etiology that may involve multiple susceptibility genes and an environmental component. To identify chromosomal loci contributing to vulnerability, we have conducted a genome-wide scan on approximately 396 individuals from 22 multiplex pedigrees by using 607 microsatellite markers. Multipoint nonparametric analysis detected the strongest evidence for linkage at 13q32 with a maximal logarithm of odds (lod) score of 3.5 (P = 0. 000028) under a phenotype model that included bipolar I, bipolar II with major depression, schizoaffective disorder, and recurrent unipolar disorder. Suggestive linkage was found on 1q31-q32 (lod = 2. 67; P = 0.00022) and 18p11.2 (lod = 2.32; P = 0.00054). Recent reports have linked schizophrenia to 13q32 and 18p11.2. Our genome scan identified other interesting regions, 7q31 (lod = 2.08; P = 0. 00099) and 22q11-q13 (lod = 2.1; P = 0.00094), and also confirmed reported linkages on 4p16, 12q23-q24, and 21q22. By comprehensive screening of the entire genome, we detected unreported loci for bipolar disorder, found support for proposed linkages, and gained evidence for the overlap of susceptibility regions for bipolar disorder and schizophrenia.

MeSH Terms
Bipolar Disorder/genetics Chromosomes, Human, Pair 1/genetics Chromosomes, Human, Pair 13/genetics Chromosomes, Human, Pair 18/genetics Genetic Linkage Genome, Human Genotype Humans Lod Score Microsatellite Repeats/genetics Pedigree Schizophrenia/genetics Statistics, Nonparametric
Authors & Affiliations
18 authors, click to expand affiliations / ORCID
Detera-Wadleigh S D
Clinical Neurogenetics Branch, National Institute of Mental Health, National Institutes of Health, Bethesda, MD 20892, USA.
Badner J A
Berrettini W H
Yoshikawa T
Goldin L R
Turner G
Rollins D Y
Moses T
Sanders A R
Karkera J D
Esterling L E
Zeng J
Ferraro T N
Guroff J J
Kazuba D
Maxwell M E
Nurnberger J I
Gershon E S
References (36)
36 references, click to expand
  1. Estimating the power of a proposed linkage study: a practical computer simulation approach.
    Am J Hum Genet. 1986 Oct;39(4):513-27 PMID: 3464203
  2. A combined analysis of D22S278 marker alleles in affected sib-pairs: support for a susceptibility locus for schizophrenia at chromosome 22q12. Schizophrenia Collaborative Linkage Group (Chromosome 22).
    Am J Med Genet. 1996 Feb 16;67(1):40-5 PMID: 8678112
  3. A controlled family study of chronic psychoses. Schizophrenia and schizoaffective disorder.
    Arch Gen Psychiatry. 1988 Apr;45(4):328-36 PMID: 3355320
  4. A genome-wide search for genes predisposing to manic-depression, assuming autosomal dominant inheritance.
    Am J Hum Genet. 1993 Jun;52(6):1234-49 PMID: 8503452
  5. Continuity and discontinuity of affective disorders and schizophrenia. Results of a controlled family study.
    Arch Gen Psychiatry. 1993 Nov;50(11):871-83 PMID: 8215813
  6. The gene for Darier's disease maps to chromosome 12q23-q24.1.
    Hum Mol Genet. 1993 Nov;2(11):1941-3 PMID: 8129825
  7. Familial cosegregation of major affective disorder and Darier's disease (keratosis follicularis)
    Br J Psychiatry. 1994 Mar;164(3):355-8 PMID: 8199789
  8. Chromosome 18 DNA markers and manic-depressive illness: evidence for a susceptibility gene.
    Proc Natl Acad Sci U S A. 1994 Jun 21;91(13):5918-21 PMID: 8016089
  9. Psychotic illness in patients diagnosed with velo-cardio-facial syndrome and their relatives.
    J Nerv Ment Dis. 1994 Aug;182(8):476-8 PMID: 8040660
  10. Affected-sib-pair interval mapping and exclusion for complex genetic traits: sampling considerations.
    Genet Epidemiol. 1996;13(2):117-37 PMID: 8722742
  11. Maternal inheritance and chromosome 18 allele sharing in unilineal bipolar illness pedigrees.
    Am J Med Genet. 1996 Apr 9;67(2):202-7 PMID: 8723048
  12. The future of genetic studies of complex human diseases.
    Science. 1996 Sep 13;273(5281):1516-7 PMID: 8801636
  13. A metric map of humans: 23,500 loci in 850 bands.
    Proc Natl Acad Sci U S A. 1996 Dec 10;93(25):14771-5 PMID: 8962130
  14. Initial genomic scan of the NIMH genetics initiative bipolar pedigrees: chromosomes 3, 5, 15, 16, 17, and 22.
    Am J Med Genet. 1997 May 31;74(3):238-46 PMID: 9184305
  15. Initial genome scan of the NIMH genetics initiative bipolar pedigrees: chromosomes 4, 7, 9, 18, 19, 20, and 21q.
    Am J Med Genet. 1997 May 31;74(3):254-62 PMID: 9184307
  16. Initial genome screen for bipolar disorder in the NIMH genetics initiative pedigrees: chromosomes 2, 11, 13, 14, and X.
    Am J Med Genet. 1997 May 31;74(3):263-9 PMID: 9184308
  17. Cytogenetic abnormalities on chromosome 18 associated with bipolar affective disorder or schizophrenia.
    Br J Psychiatry. 1997 Mar;170:278-80 PMID: 9229037
  18. Allele-sharing models: LOD scores and accurate linkage tests.
    Am J Hum Genet. 1997 Nov;61(5):1179-88 PMID: 9345087
  19. An integrated physical map of 18p11.2: a susceptibility region for bipolar disorder.
    Mol Psychiatry. 1997 Oct-Nov;2(6):501-4 PMID: 9399696
  20. Linkage of bipolar affective disorder to chromosome 18 markers in a new pedigree series.
    Am J Hum Genet. 1997 Dec;61(6):1397-404 PMID: 9399888
  21. Affective disorder associated with a balanced translocation involving chromosome 14 and 18.
    Psychiatr Genet. 1998 Summer;8(2):53-6 PMID: 9686423
  22. Optimal ascertainment strategies to detect linkage to common disease alleles.
    Am J Hum Genet. 1998 Sep;63(3):880-8 PMID: 9718337
  23. Schizophrenia susceptibility loci on chromosomes 13q32 and 8p21.
    Nat Genet. 1998 Sep;20(1):70-3 PMID: 9731535
  24. Support for a chromosome 18p locus conferring susceptibility to functional psychoses in families with schizophrenia, by association and linkage analysis.
    Am J Hum Genet. 1998 Oct;63(4):1139-52 PMID: 9758604
  25. Significant linkage between bipolar affective disorder and chromosome 12q24.
    Psychiatr Genet. 1998 Autumn;8(3):131-40 PMID: 9800214
  26. Genetic linkage mapping for a susceptibility locus to bipolar illness: chromosomes 2, 3, 4, 7, 9, 10p, 11p, 22, and Xpter.
    Am J Med Genet. 1994 Sep 15;54(3):206-18 PMID: 7810578
  27. A possible vulnerability locus for bipolar affective disorder on chromosome 21q22.3.
    Nat Genet. 1994 Nov;8(3):291-6 PMID: 7874172
  28. Type I bipolar disorder associated with a fragile site on chromosome 1.
    Am J Med Genet. 1995 Jun 19;60(3):179-82 PMID: 7573167
  29. Genetic dissection of complex traits: guidelines for interpreting and reporting linkage results.
    Nat Genet. 1995 Nov;11(3):241-7 PMID: 7581446
  30. Evidence for linkage of bipolar disorder to chromosome 18 with a parent-of-origin effect.
    Am J Hum Genet. 1995 Dec;57(6):1384-94 PMID: 8533768
  31. Affected-sib-pair analyses reveal support of prior evidence for a susceptibility locus for bipolar disorder, on 21q.
    Am J Hum Genet. 1996 Jun;58(6):1279-85 PMID: 8651306
  32. Parametric and nonparametric linkage analysis: a unified multipoint approach.
    Am J Hum Genet. 1996 Jun;58(6):1347-63 PMID: 8651312
  33. A manic depressive history.
    Nat Genet. 1996 Apr;12(4):351-3 PMID: 8630482
  34. A locus for bipolar affective disorder on chromosome 4p.
    Nat Genet. 1996 Apr;12(4):427-30 PMID: 8630499
  35. Genetic mapping using haplotype, association and linkage methods suggests a locus for severe bipolar disorder (BPI) at 18q22-q23.
    Nat Genet. 1996 Apr;12(4):436-41 PMID: 8630501
  36. The continuum of psychosis and its implication for the structure of the gene.
    Br J Psychiatry. 1986 Oct;149:419-29 PMID: 3814925
Article Info
Journal
Proceedings of the National Academy of Sciences of the United States of America
Abbr.
Proc Natl Acad Sci U S A
ISSN
0027-8424
DOI
10.1073/pnas.96.10.5604
Published
1999-05-11
Pages
5604-9
Language
English
Region
United States
NLM ID
7505876
PMCID
PMC21907
Subset
IM
External Links
PubMed source DOI: 10.1073/pnas.96.10.5604 PMC Full Text View journal details
Analysis Services
Analysis Services

Contact

No. 2 Wenbo Road, Zhangqiu District, Jinan, Shandong

Qilu Normal University · Genelibs Bioinformatics Lab

750 Shunhua Rd, Jinan

2F, Bldg F, University Science Park

Tel: 0531-88819269

WeChat Official Account

Follow our WeChat subscription account for real-time updates and the latest in medical and biological research.


Business Email

E-mail: product@genelibs.com

Copyright © 2026.Genelibs Jinan Honghui Biotechnology Co., Ltd. 鲁ICP备20007159号-2