Genome scan of the fifty-six bipolar pedigrees from the NIMH genetics initiative replication sample: Chromosomes 4, 7, 9, 18, 19, 20, and 21

Virginia L. Willour, Peter P. Zandi, Yuqing Huo, Tyra L. Diggs, Jennifer L. Chellis, Dean F. MacKinnon, Sylvia G. Simpson, Francis J. McMahon, James B. Potash, Elliot S. Gershon, Theodore Reich, Tatiana Foroud, John Nurnberger, J. Raymond DePaulo, Melvin G. McInnis

Research output: Contribution to journalArticle

25 Citations (Scopus)

Abstract

The NIMH genetics initiative on bipolar disorder was established to collect uniformly ascertained bipolar pedigrees for genetic studies. In 1997, the four participating sites published a genome scan on the initial set of 97 bipolar pedigrees. Fifty-six additional bipolar pedigrees have nowbeen ascertained and evaluated. This replication pedigree set contains 354 genotyped subjects, including 139 bipolar I (BPI) subjects, five schizoaffective bipolar type SA/BP subjects, 41 bipolar II (BPII) subjects, and 43 recurrent unipolar (RUP) depression subjects. Our site has recently genotyped the replication study bipolar pedigrees using 107 microsatellite markers from chromosomes 4, 7, 9, 18, 19, 20, and 21. We are now reporting parametric and nonparametric linkage results from this effort. Multipoint nonparametric linkage analysis produced three candidate regions with allele sharing LOD scores ≥ 1.0. The linkage signal on 4q35 peaked between markers D4S3335 and D4S2390 with an allele sharing LOD score of 2.49. This finding exceeds standard criteria for suggestive linkage. Two additional loci approach suggestive linkage levels: the 4q32 finding had its maximum near marker D4S1629 with an allele sharing LOD score of 2.16, and the 20p12 finding peaked at D20S162 with an allele sharing LOD score of 1.82. Multipoint parametric linkage analysis produced similar findings. When we combined the genotype data from the original and the replication pedigree sets, 20p12 yielded a nonparametric LOD score of 2.38, which exceeds standard criteria for suggestive linkage, and a corresponding parametric HLOD score of 2.98. The combined analysis did not provide further support for linkage to 4q32 and 4q35.

Original languageEnglish
Pages (from-to)21-27
Number of pages7
JournalAmerican Journal of Medical Genetics, Part B: Neuropsychiatric Genetics
Volume121 B
Issue number1
StatePublished - Aug 15 2003

Fingerprint

National Institute of Mental Health (U.S.)
Chromosomes, Human, Pair 4
Chromosomes, Human, Pair 7
Pedigree
Genome
Alleles
Depressive Disorder
Bipolar Disorder
Microsatellite Repeats
Genotype

Keywords

  • 20p
  • 4q
  • Manic depression
  • Nonparametric linkage
  • Parametric linkage

ASJC Scopus subject areas

  • Genetics(clinical)
  • Neuropsychology and Physiological Psychology
  • Neuroscience(all)

Cite this

Genome scan of the fifty-six bipolar pedigrees from the NIMH genetics initiative replication sample : Chromosomes 4, 7, 9, 18, 19, 20, and 21. / Willour, Virginia L.; Zandi, Peter P.; Huo, Yuqing; Diggs, Tyra L.; Chellis, Jennifer L.; MacKinnon, Dean F.; Simpson, Sylvia G.; McMahon, Francis J.; Potash, James B.; Gershon, Elliot S.; Reich, Theodore; Foroud, Tatiana; Nurnberger, John; DePaulo, J. Raymond; McInnis, Melvin G.

In: American Journal of Medical Genetics, Part B: Neuropsychiatric Genetics, Vol. 121 B, No. 1, 15.08.2003, p. 21-27.

Research output: Contribution to journalArticle

Willour, VL, Zandi, PP, Huo, Y, Diggs, TL, Chellis, JL, MacKinnon, DF, Simpson, SG, McMahon, FJ, Potash, JB, Gershon, ES, Reich, T, Foroud, T, Nurnberger, J, DePaulo, JR & McInnis, MG 2003, 'Genome scan of the fifty-six bipolar pedigrees from the NIMH genetics initiative replication sample: Chromosomes 4, 7, 9, 18, 19, 20, and 21', American Journal of Medical Genetics, Part B: Neuropsychiatric Genetics, vol. 121 B, no. 1, pp. 21-27.
Willour, Virginia L. ; Zandi, Peter P. ; Huo, Yuqing ; Diggs, Tyra L. ; Chellis, Jennifer L. ; MacKinnon, Dean F. ; Simpson, Sylvia G. ; McMahon, Francis J. ; Potash, James B. ; Gershon, Elliot S. ; Reich, Theodore ; Foroud, Tatiana ; Nurnberger, John ; DePaulo, J. Raymond ; McInnis, Melvin G. / Genome scan of the fifty-six bipolar pedigrees from the NIMH genetics initiative replication sample : Chromosomes 4, 7, 9, 18, 19, 20, and 21. In: American Journal of Medical Genetics, Part B: Neuropsychiatric Genetics. 2003 ; Vol. 121 B, No. 1. pp. 21-27.
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