A high-density genome scan detects evidence for a bipolar-disorder susceptibility locus on 13q32 and other potential loci on 1q32 and 18p11.2
Sevilla D. Detera-Wadleigh,Judith A. Badner,Judith A. Badner,Wade H. Berrettini,Takeo Yoshikawa,Lynn R. Goldin,Gordon Turner,D. Y. Rollins,Tracy Moses,Alan R. Sanders,Alan R. Sanders,Jayaprakash D. Karkera,Lisa E. Esterling,Jin Zeng,Thomas N. Ferraro,Juliet J. Guroff,Diane Kazuba,M. E. Maxwell,John I. Nurnberger,Elliot S. Gershon,Elliot S. Gershon +20 more
TLDR
By comprehensive screening of the entire genome, a genome-wide scan is conducted on approximately 396 individuals from 22 multiplex pedigrees by using 607 microsatellite markers to detect unreported loci for bipolar disorder, found support for proposed linkages, and gained evidence for the overlap of susceptibility regions for bipolar Disorder and schizophrenia.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.read more
Citations
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Disruption of two novel genes by a translocation co-segregating with schizophrenia
J. Kirsty Millar,Julie C. Wilson-Annan,Susan Anderson,Sheila Christie,Martin S. Taylor,Collin A.M. Semple,Rebecca S. Devon,David St Clair,Walter J. Muir,Douglas Blackwood,David J. Porteous +10 more
TL;DR: Observations indicate that DISC1 and DISC2 should be considered formal candidate genes for susceptibility to psychiatric illness.
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Convergent evidence for impaired AKT1-GSK3beta signaling in schizophrenia.
TL;DR: It is shown that haloperidol induces a stepwise increase in regulatory phosphorylation of AKT1 in the brains of treated mice that could compensate for an impaired function of this signaling pathway in schizophrenia.
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Meta-analysis of whole-genome linkage scans of bipolar disorder and schizophrenia
TL;DR: Simulations demonstrated that the type I error rate was at least as low as that for a single genome scan and thus genome-wide significance criteria may be applied, and power to detect linkage wasat least as high as the power of pooling the data from all the studies.
Journal ArticleDOI
Schizophrenia and Affective Disorders—Cosegregation with a Translocation at Chromosome 1q42 That Directly Disrupts Brain-Expressed Genes: Clinical and P300 Findings in a Family
Douglas Blackwood,Douglas Blackwood,A. Fordyce,M. Walker,D St Clair,David J. Porteous,Walter J. Muir,Walter J. Muir +7 more
TL;DR: The results of karyotypic, clinical, and ERP investigations of this family suggest that the recently described genes DISC1 and DISC2, which are directly disrupted by the breakpoint on chromosome 1, may have a role in the development of a disease phenotype that includes schizophrenia as well as unipolar and bipolar affective disorders.
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The brain-derived neurotrophic factor gene confers susceptibility to bipolar disorder: evidence from a family-based association study.
Maria Neves-Pereira,Emanuela Mundo,Pierandrea Muglia,Nicole King,Fabio Macciardi,James L. Kennedy +5 more
TL;DR: Test for the presence of linkage disequilibrium between two polymorphisms in the BDNF gene and BP in 283 nuclear families found it unlikely that the actual risk-conferring allele is from these two sites, but suggests that a DNA variant in the vicinity of the BD NF locus confers susceptibility to BP.
References
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Genetic dissection of complex traits: guidelines for interpreting and reporting linkage results
Eric S. Lander,Leonid Kruglyak +1 more
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Schizophrenia susceptibility loci on chromosomes 13q32 and 8p21
Jean-Louis Blouin,Beth A. Dombroski,Swapan K. Nath,Virginia K. Lasseter,Paula S. Wolyniec,Gerald Nestadt,Mary H. Thornquist,Gail Ullrich,John J. McGrath,Laura Kasch,Malgorzata Lamacz,Marion Thomas,Corinne Gehrig,Uppala Radhakrishna,Sarah E. Snyder,Katherine G. Balk,Karin J. Neufeld,Karen Swartz,Nicola DeMarchi,George N. Papadimitriou,Dimitris Dikeos,Costas N. Stefanis,Aravinda Chakravarti,Barton Childs,David E. Housman,Haig H. Kazazian,Stylianos E. Antonarakis,Ann E. Pulver +27 more
TL;DR: A genome-wide scan for schizophrenia susceptibility loci (SSL) using 452 microsatellite markers on 54 multiplex pedigrees is presented and it is more probable that chromosome 8 may be a false positive linkage.
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