title: A genome-wide linkage scan of bipolar disorder in Latino families identifies susceptibility loci at 8q24 and 14q32.
abstract: A genome-wide nonparametric linkage screen was performed to localize Bipolar Disorder (BP) susceptibility loci in a sample of 3757 individuals of Latino ancestry. The sample included 963 individuals with BP phenotype (704 relative pairs) from 686 families recruited from the US, Mexico, Costa Rica, and Guatemala. Non-parametric analyses were performed over a 5 cM grid with an average genetic coverage of 0.67 cM. Multipoint analyses were conducted across the genome using non-parametric Kong & Cox LOD scores along with Sall statistics for all relative pairs. Suggestive and significant genome-wide thresholds were calculated based on 1000 simulations. Single-marker association tests in the presence of linkage were performed assuming a multiplicative model with a population prevalence of 2%. We identified two genome-wide significant susceptibly loci for BP at 8q24 and 14q32, and a third suggestive locus at 2q13-q14. Within these three linkage regions, the top associated single marker (rs1847694, P = 2.40 × 10(-5)) is located 195 Kb upstream of DPP10 in Chromosome 2. DPP10 is prominently expressed in brain neuronal populations, where it has been shown to bind and regulate Kv4-mediated A-type potassium channels. Taken together, these results provide additional evidence that 8q24, 14q32, and 2q13-q14 are susceptibly loci for BP and these regions may be involved in the pathogenesis of BP in the Latino population.
authors.affiliation: Center of Excellence for Neurosciences, Paul L. Foster School of Medicine, Texas Tech University Health Sciences Center, El Paso, Texas; Department of Psychiatry, Paul L. Foster School of Medicine, Texas Tech University Health Sciences Center, El Paso, Texas.
authors.forename: Suzanne
authors.initials: S
authors.lastname: Gonzalez
authors.forename: Cynthia
authors.initials: C
authors.lastname: Camarillo
authors.forename: Marco
authors.initials: M
authors.lastname: Rodriguez
authors.forename: Mercedes
authors.initials: M
authors.lastname: Ramirez
authors.forename: Juan
authors.initials: J
authors.lastname: Zavala
authors.forename: Regina
authors.initials: R
authors.lastname: Armas
authors.forename: Salvador A
authors.initials: SA
authors.lastname: Contreras
authors.forename: Javier
authors.initials: J
authors.lastname: Contreras
authors.forename: Albana
authors.initials: A
authors.lastname: Dassori
authors.forename: Laura
authors.initials: L
authors.lastname: Almasy
authors.forename: Deborah
authors.initials: D
authors.lastname: Flores
authors.forename: Alvaro
authors.initials: A
authors.lastname: Jerez
authors.forename: Henriette
authors.initials: H
authors.lastname: Raventós
authors.forename: Alfonso
authors.initials: A
authors.lastname: Ontiveros
authors.forename: Humberto
authors.initials: H
authors.lastname: Nicolini
authors.forename: Michael
authors.initials: M
authors.lastname: Escamilla
mesh_terms: D001714:Bipolar Disorder / Q000235:genetics*; D002883:Chromosomes, Human, Pair 14 / Q000235:genetics*; D002898:Chromosomes, Human, Pair 8 / Q000235:genetics*; D005190:Family; D008040:Genetic Linkage; D056426:Genetic Loci / Q000235:genetics*; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D006630:Hispanic or Latino / Q000235:genetics*; D006801:Humans; D008957:Models, Genetic; D010641:Phenotype; D017422:Sequence Analysis, DNA; D018709:Statistics, Nonparametric
keywords: Central-American; Mexican; Mexican-American; bipolar disorder; family studies; genetics