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Am J Med Genet B Neuropsychiatr Genet. 2019 Apr;180(3):213-222. doi: 10.1002/ajmg.b.32715. Epub 2019 Feb 19.

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

Author information

1
Center of Emphasis in Neurosciences, Department of Biomedical Sciences, Paul L. Foster School of Medicine, Texas Tech University Health Sciences Center, El Paso, Texas.
2
Departments of Psychiatry and Pharmacology, Penn State College of Medicine, Hershey, Pennsylvania.
3
Department of Bioinformatics, University of Texas Southwestern Medical Center, Dallas, Texas.
4
Department of Psychiatry, Paul L. Foster School of Medicine, Texas Tech University Health Sciences Center, El Paso, Texas.
5
Langley Porter Psychiatric Institute, University of California at San Francisco, San Francisco, California.
6
Department of Psychiatry, University of Texas Health Science Center at San Antonio, San Antonio, Texas.
7
Department of Psychiatry, South Texas Veterans Health Care System, San Antonio, Texas.
8
Centro de Investigación en Biología Celular y Molecular y Escuela de Biologia, Universidad de Costa Rica, San Jose, Costa Rica.
9
Los Angeles Biomedical Research Center at Harbor, University of California Los Angeles Medical Center, Torrance, California.
10
Centro Internacional de Trastornos Afectivos y de la Conducta Adictiva, Guatemala City, Guatemala.
11
Departamento de Psiquiatria, Hospital Universitario UANL, Monterrey, Nuevo Leon, Mexico.
12
Grupo de Estudios Médicos y Familiares Carracci S.C., México, Distrito Federal, Mexico.
13
Laboratorio de Enfermedades Psychiatricas y Neurodegenerativas, Instituto Nacional de Medicina Genómica, México, Distrito Federal, Mexico.

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.

KEYWORDS:

ACTR3; DPP10; FBXO32; Latino ancestry; bipolar disorder

PMID:
30779416
DOI:
10.1002/ajmg.b.32715

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