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Am J Med Genet B Neuropsychiatr Genet ; 180(3): 213-222, 2019 04.
Article in English | MEDLINE | ID: mdl-30779416

ABSTRACT

We previously identified bipolar disorder (BD) susceptibility loci on 8q24, 14q32, and 2q12-14 in a genome-wide nonparametric linkage screen in a Latino cohort. We now perform a fine mapping analysis using a dense map of additional SNPs to identify BD susceptibility genes within these regions. One thousand nine hundred and thirty-eight individuals with Latino ancestry (880 individuals with BD Type I or Schizoaffective, Bipolar Type) from 416 Latino pedigrees from the United States, Mexico, Costa Rica, and Guatemala were genotyped with 3,074 SNPs to provide dense coverage of the 8q24 (11.5 cM), 14q32 (7.5 cM), and 2q12-14 (6.5 cM) chromosomal loci. Single-marker association tests in the presence of linkage were performed using the LAMP software. The top linkage peak (rs7834818; LOD = 5.08, p = 3.30E - 5) and associated single marker (rs2280915, p = 2.70E - 12) were located within FBXO32 on 8q24. On chromosome 2, the top linkage peak (rs6750326; LOD = 5.06, p = 3.50E - 5) and associated single marker (rs11887088, p = 2.90E - 6) were located in intragenic regions near ACTR3 and DPP10. None of the additional markers in the region around chromosome 14q32 met significance levels for linkage or association. We identified six SNPs on 2q12-q14 and one SNP in FBXO32 on 8q24 that were significantly associated with BD in this Latino cohort.


Subject(s)
Bipolar Disorder/genetics , Chromosomes, Human, Pair 2/genetics , Psychotic Disorders/genetics , Actin-Related Protein 3/genetics , Actin-Related Protein 3/metabolism , Adult , Bipolar Disorder/psychology , Chromosome Mapping/methods , Costa Rica , Dipeptidyl-Peptidases and Tripeptidyl-Peptidases/genetics , Dipeptidyl-Peptidases and Tripeptidyl-Peptidases/metabolism , Female , Genetic Linkage/genetics , Genetic Predisposition to Disease/genetics , Genome-Wide Association Study/methods , Genotype , Guatemala , Hispanic or Latino/genetics , Humans , Lod Score , Male , Mexico , Middle Aged , Muscle Proteins/genetics , Muscle Proteins/metabolism , Polymorphism, Single Nucleotide/genetics , Psychotic Disorders/psychology , SKP Cullin F-Box Protein Ligases/genetics , SKP Cullin F-Box Protein Ligases/metabolism , United States
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