title: Replication of genome-wide association study (GWAS) susceptibility loci in a Latino bipolar disorder cohort.
abstract: Recent genome-wide association studies (GWASs) have identified numerous putative genetic polymorphisms associated with bipolar disorder (BD) and/or schizophrenia (SC). We hypothesized that a portion of these polymorphisms would also be associated with BD in the Latino American population. To identify such regions, we tested previously identified genetic variants associated with BD and/or SC and ancestral haploblocks containing these single nucleotide polymorphisms (SNPs) in a sample of Latino subjects with BD.
  
  
  
  A total of 2254 Latino individuals were genotyped for 91 SNPs identified in previous BD and/or SC GWASs, along with selected SNPs in strong linkage disequilibrium with these markers. Family-based single marker and haplotype association testing was performed using the PBAT software package. Empirical P-values were derived from 10 000 permutations.
  
  
  
  Associations of eight a priori GWAS SNPs with BD were replicated with nominal (P≤.05) levels of significance. These included SNPs within nuclear factor I A (NFIA), serologically defined colon cancer antigen 8 (SDCCAG8), lysosomal associated membrane protein 3 (LAMP3), nuclear factor kappa B subunit 1 (NFKB1), major histocompatibility complex, class I, B (HLA-B) and 5'-nucleotidase, cytosolic II (NT5C2) and SNPs within intragenic regions microRNA 6828 (MIR6828)-solute carrier family 7 member 14 (SLC7A14) and sonic hedgehog (SHH)-long intergenic non-protein coding RNA 1006 (LINC01006). Of the 76 ancestral haploblocks that were tested for associations with BD, our top associated haploblock was located in LAMP3; however, the association did not meet statistical thresholds of significance following Bonferroni correction.
  
  
  
  These results indicate that some of the gene variants found to be associated with BD or SC in other populations are also associated with BD risk in Latinos. Variants in six genes and two intragenic regions were associated with BD in our Latino sample and provide additional evidence for overlap in genetic risk between SC and BD.
authors.affiliation: Center of Excellence in Neurosciences, Department of Biomedical Sciences, Paul L. Foster School of Medicine, Texas Tech University Health Sciences Center, El Paso, TX, USA. suzanne.gonzalez@ttuhsc.edu.
authors.forename: Suzanne
authors.initials: S
authors.lastname: Gonzalez
authors.affiliation: Department of Health Sciences, College of Health Professions & Social Work, Florida Gulf Coast University, Fort Myers, FL, USA.
authors.forename: Jayanta
authors.initials: J
authors.lastname: Gupta
authors.affiliation: Center of Excellence in Neurosciences, Department of Biomedical Sciences, Paul L. Foster School of Medicine, Texas Tech University Health Sciences Center, El Paso, TX, USA.
authors.forename: Erika
authors.initials: E
authors.lastname: Villa
authors.affiliation: Biostatistics and Epidemiology Consulting Lab, Paul L. Foster School of Medicine, Texas Tech University Health Sciences Center, El Paso, TX, USA.
authors.forename: Indika
authors.initials: I
authors.lastname: Mallawaarachchi
authors.affiliation: Center of Excellence in Neurosciences, Department of Biomedical Sciences, Paul L. Foster School of Medicine, Texas Tech University Health Sciences Center, El Paso, TX, USA.
authors.forename: Marco
authors.initials: M
authors.lastname: Rodriguez
authors.affiliation: Center of Excellence in Neurosciences, Department of Biomedical Sciences, Paul L. Foster School of Medicine, Texas Tech University Health Sciences Center, El Paso, TX, USA.|Department of Psychiatry, Paul L. Foster School of Medicine, Texas Tech University Health Sciences Center, El Paso, TX, USA.
authors.forename: Mercedes
authors.initials: M
authors.lastname: Ramirez
authors.affiliation: Center of Excellence in Neurosciences, Department of Biomedical Sciences, Paul L. Foster School of Medicine, Texas Tech University Health Sciences Center, El Paso, TX, USA.|Department of Psychiatry, Paul L. Foster School of Medicine, Texas Tech University Health Sciences Center, El Paso, TX, USA.
authors.forename: Juan
authors.initials: J
authors.lastname: Zavala
authors.affiliation: Langley Porter Psychiatric Institute, University of California at San Francisco, San Francisco, CA, USA.
authors.forename: Regina
authors.initials: R
authors.lastname: Armas
authors.affiliation: Department of Psychiatry, University of Texas Health Science Center at San Antonio, San Antonio, TX, USA.|South Texas Veterans Health Care System, San Antonio, TX, USA.
authors.forename: Albana
authors.initials: A
authors.lastname: Dassori
authors.affiliation: Centro de Investigación en Biología Celular y Molecular y Escuela de Biologia, Universidad de Costa Rica, San Jose, Costa Rica.
authors.forename: Javier
authors.initials: J
authors.lastname: Contreras
authors.affiliation: Los Angeles Biomedical Research Center at Harbor, University of California Los Angeles Medical Center, Torrance, CA, USA.
authors.forename: Deborah
authors.initials: D
authors.lastname: Flores
authors.affiliation: Centro Internacional de Trastornos Afectivos y de la Conducta Adictiva, Guatemala City, Guatemala.
authors.forename: Alvaro
authors.initials: A
authors.lastname: Jerez
authors.affiliation: Instituto de Información e Investigación en Salud Mental AC, Monterrey, Nuevo Leon, México.
authors.forename: Alfonso
authors.initials: A
authors.lastname: Ontiveros
authors.affiliation: Grupo de Estudios Médicos y Familiares Carracci S.C., México D.F, México.
authors.forename: Humberto
authors.initials: H
authors.lastname: Nicolini
authors.affiliation: Center of Excellence in Neurosciences, Department of Biomedical Sciences, Paul L. Foster School of Medicine, Texas Tech University Health Sciences Center, El Paso, TX, USA.|Department of Psychiatry, Paul L. Foster School of Medicine, Texas Tech University Health Sciences Center, El Paso, TX, USA.
authors.forename: Michael
authors.initials: M
authors.lastname: Escamilla
mesh_terms: D000328:Adult; D001714:Bipolar Disorder / Q000208:ethnology / Q000235:genetics; D003364:Costa Rica / Q000453:epidemiology; D005260:Female; D020022:Genetic Predisposition to Disease; D005820:Genetic Testing; D055106:Genome-Wide Association Study; D006166:Guatemala / Q000453:epidemiology; D006239:Haplotypes; D006630:Hispanic or Latino / Q000235:genetics / Q000706:statistics & numerical data; D006801:Humans; D051741:Kruppel-Like Transcription Factors / Q000235:genetics*; D015810:Linkage Disequilibrium; D051907:Lysosomal Membrane Proteins / Q000235:genetics*; D008297:Male; D008800:Mexico / Q000453:epidemiology; D052002:NF-kappa B p50 Subunit / Q000235:genetics*; D009363:Neoplasm Proteins / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D012559:Schizophrenia / Q000208:ethnology / Q000235:genetics; D014481:United States / Q000453:epidemiology; D059666:Lysosomal-Associated Membrane Protein 3
chemical_list: D051741:Kruppel-Like Transcription Factors; D051907:Lysosomal Membrane Proteins; D052002:NF-kappa B p50 Subunit; D009363:Neoplasm Proteins; C114233:LAMP3 protein, human; D059666:Lysosomal-Associated Membrane Protein 3; C489548:NFKB1 protein, human; C540527:ZNF804A protein, human
keywords: Central American; Latinos; Mexican; Mexican-American; bipolar disorder; family studies; genetics; lysosomal associated membrane protein 3 (LAMP3); nuclear factor kappa B subunit 1 (NFKB1); serologically defined colon cancer antigen 8 (SDCCAG8)