Fine-mapping scan of bipolar disorder susceptibility loci in Latino pedigrees

Suzanne Gonzalez, Erika Villa, Marco Rodriguez, Mercedes Ramirez, Juan Zavala, Regina Armas, Albana Dassori, Javier Contreras, Henriette Raventós, Deborah Flores, Alvaro Jerez, Alfonso Ontiveros, Humberto Nicolini, Michael Escamilla

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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.

Original languageEnglish (US)
Pages (from-to)213-222
Number of pages10
JournalAmerican Journal of Medical Genetics, Part B: Neuropsychiatric Genetics
Volume180
Issue number3
DOIs
StatePublished - Apr 2019

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Keywords

  • ACTR3
  • DPP10
  • FBXO32
  • Latino ancestry
  • bipolar disorder

ASJC Scopus subject areas

  • Genetics(clinical)
  • Psychiatry and Mental health
  • Cellular and Molecular Neuroscience

Cite this

Gonzalez, S., Villa, E., Rodriguez, M., Ramirez, M., Zavala, J., Armas, R., Dassori, A., Contreras, J., Raventós, H., Flores, D., Jerez, A., Ontiveros, A., Nicolini, H., & Escamilla, M. (2019). Fine-mapping scan of bipolar disorder susceptibility loci in Latino pedigrees. American Journal of Medical Genetics, Part B: Neuropsychiatric Genetics, 180(3), 213-222. https://doi.org/10.1002/ajmg.b.32715