title: Results of a SNP genome screen in a large Costa Rican pedigree segregating for severe bipolar disorder.
abstract: We have ascertained in the Central Valley of Costa Rica a new kindred (CR201) segregating for severe bipolar disorder (BP-I). The family was identified by tracing genealogical connections among eight persons initially independently ascertained for a genome wide association study of BP-I. For the genome screen in CR201, we trimmed the family down to 168 persons (82 of whom are genotyped), containing 25 individuals with a best-estimate diagnosis of BP-I. A total of 4,690 SNP markers were genotyped. Analysis of the data was hampered by the size and complexity of the pedigree, which prohibited using exact multipoint methods on the entire kindred. Two-point parametric linkage analysis, using a conservative model of transmission, produced a maximum LOD score of 2.78 on chromosome 6, and a total of 39 loci with LOD scores >1.0. Multipoint parametric and non-parametric linkage analysis was performed separately on four sections of CR201, and interesting (nominal P-value from either analysis <0.01), although not statistically significant, regions were highlighted on chromosomes 1, 2, 3, 12, 16, 19, and 22, in at least one section of the pedigree, or when considering all sections together. The difficulties of analyzing genome wide SNP data for complex disorders in large, potentially informative, kindreds are discussed.
authors.affiliation: Center for Neurobehavioral Genetics, University of California, Los Angeles, 90095-1761, USA.
authors.forename: Susan
authors.initials: S
authors.lastname: Service
authors.forename: Julio
authors.initials: J
authors.lastname: Molina
authors.forename: Joseph
authors.initials: J
authors.lastname: Deyoung
authors.forename: Damini
authors.initials: D
authors.lastname: Jawaheer
authors.forename: Ileana
authors.initials: I
authors.lastname: Aldana
authors.forename: Thuy
authors.initials: T
authors.lastname: Vu
authors.forename: Carmen
authors.initials: C
authors.lastname: Araya
authors.forename: Xinia
authors.initials: X
authors.lastname: Araya
authors.forename: Julio
authors.initials: J
authors.lastname: Bejarano
authors.forename: Eduardo
authors.initials: E
authors.lastname: Fournier
authors.forename: Magui
authors.initials: M
authors.lastname: Ramirez
authors.forename: Carol A
authors.initials: CA
authors.lastname: Mathews
authors.forename: Pablo
authors.initials: P
authors.lastname: Davanzo
authors.forename: Gabriel
authors.initials: G
authors.lastname: Macaya
authors.forename: Lodewijk
authors.initials: L
authors.lastname: Sandkuijl
authors.forename: Chiara
authors.initials: C
authors.lastname: Sabatti
authors.forename: Victor
authors.initials: V
authors.lastname: Reus
authors.forename: Nelson
authors.initials: N
authors.lastname: Freimer
mesh_terms: D001714:Bipolar Disorder / Q000175:diagnosis / Q000235:genetics*; D003364:Costa Rica; D005260:Female; D008040:Genetic Linkage; D005819:Genetic Markers / Q000235:genetics; D020022:Genetic Predisposition to Disease / Q000235:genetics; D005820:Genetic Testing; D015894:Genome, Human / Q000235:genetics*; D005838:Genotype; D006801:Humans; D008126:Lod Score; D008297:Male; D010375:Pedigree; D020641:Polymorphism, Single Nucleotide
chemical_list: D005819:Genetic Markers