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ABSTRACT: A region between D13S71 and D13S274 on 13q32 showed linkage to bipolar disorder (BP) based on a genome scan using markers with an average spacing of ∼6 cM and an average heterozygosity of ∼60% [Detera-Wadleigh et al., 1999: Proc Natl Acad Sci USA 96:5604–5609]. In an attempt to confirm this finding and achieve fine mapping of the susceptibility region, nine additional microsatellite markers with average heterozygosity of ∼86%, located between D13S71 and D13S274, were typed in the same sample. The strongest linkage evidence was detected by multipoint linkage analysis (ASPEX program) around D13S779–D13S225 with maximum LOD score of 3.25 under Affection Status Model II (ASM II; P = 0.0000546). Data from additional nine markers resulted in a decrease of the 95% confidence interval of the linkage region. Association analyses with GASSOC TDT and ASPEX/sib_tdt detect potential linkage disequilibrium with several markers, including D13S280 (ASPEX TDT P = 0.0033, ASM I). These data generated using a higher marker density within the proposed susceptibility region strengthen the validity of our previous findings and suggest a finer localization of the susceptibility gene(s) on 13q32. © 2001 Wiley-Liss, Inc.
American Journal of Medical Genetics 05/2001; 105(4):375 - 380.
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Sevilla D Detera-Wadleigh,
Judith A Badner,
Wade H Berrettini,
Takeo Yoshikawa,
Lynn R Goldin,
Gordon Turner,
Denise Y. Rollins,
Tracy Moses,
Alan R. Sanders,
Jayaprakash D. Karkera,
Lisa E. Esterling,
Jin Zeng,
Thomas N Ferraro, Juliet J. Guroff,
Diane Kazuba,
Mary E. Maxwell,
John I Nurnberger,
Elliot S Gershon
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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 ≈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.
Proceedings of the National Academy of Sciences 06/1999; · 9.68 Impact Factor
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Sevilla D. Detera-Wadleigh,
Judith A. Badner,
Wade H. Berrettini,
Takeo Yoshikawa,
Lynn R. Goldin,
Gordon Turner,
Denise Y. Rollins,
Tracy Moses,
Alan R. Sanders,
Jayaprakash D. Karkera,
Lisa E. Esterling,
Jin Zeng,
Thomas N. Ferraro, Juliet J. Guroff,
Diane Kazuba,
Mary E. Maxwell,
Jr. John I. Nurnberger,
Elliot S. Gershon
[show abstract]
[hide abstract]
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 ≈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.
Proceedings of the National Academy of Sciences 05/1999; 96(10):5604-5609. · 9.68 Impact Factor
