Results of a SNP genome screen in a large Costa Rican pedigree segregating for severe bipolar disorder.
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.
Service
Susan
S
Center for Neurobehavioral Genetics, University of California, Los Angeles, 90095-1761, USA.
Molina
Julio
J
Deyoung
Joseph
J
Jawaheer
Damini
D
Aldana
Ileana
I
Vu
Thuy
T
Araya
Carmen
C
Araya
Xinia
X
Bejarano
Julio
J
Fournier
Eduardo
E
Ramirez
Magui
M
Mathews
Carol A
CA
Davanzo
Pablo
P
Macaya
Gabriel
G
Sandkuijl
Lodewijk
L
Sabatti
Chiara
C
Reus
Victor
V
Freimer
Nelson
N
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
D005819:Genetic Markers