Genome-wide scan for linkage to schizophrenia in a Spanish-origin cohort from Costa Rica.
Genetic isolates have been useful cohorts in which to search for genes underlying disorders of unknown pathology. One such cohort is thought to exist in the Central Valley of Costa Rica surrounding the city of San Jose. Previous investigators identified a rare dominant gene for hereditary deafness in this population, and a suggestive linkage of severe bipolar psychosis has been reported in another study. Ninety-nine families with at least one pair of siblings affected with schizophrenia or a schizophrenia-spectrum diagnosis had clinical evaluations and DNA collected for genotyping. The Marshfield Medical Research Foundation (NHLBI) Mammalian Genotyping Service performed all genotyping using 404 short-tandem repeat polymorphic markers (STRPs) spaced on average 10 cM apart. Data were analyzed using the nonparametric program, GeneHunterPlus. The population structure was investigated using the STRUCT program. No region was found with genome-wide significance for linkage. Using a phenotype of schizophrenia plus schizoaffective disorder, the highest maximum likelihood score (MLS) observed was 1.78 (P < 0.004) at 176.6 cM from pter on chromosome 5q, an area previously implicated by some other groups. In addition, five regions on chromosomes 1p, 2p, 2q, 14p, and 8p had MLSs above 1.0. All other regions produced scores below 1.0. Population genetic analysis reveals no evidence for population substructure, for admixture with other populations, such as Amerindians, or for inbreeding in the parental generation. The latter casts some doubt on this population being an isolate, although there was evidence of inbreeding among the offspring.
Department of Psychiatry, New York University, Millhauser Laboratories, New York, New York 10016, USA. DeLisi76@aol.com
Lynn E
LE
DeLisi
Andrea
A
Mesen
Carlos
C
Rodriguez
Arturo
A
Bertheau
Beatrice
B
LaPrade
Michelle
M
Llach
Silvina
S
Riondet
Kamran
K
Razi
Margaret
M
Relja
William
W
Byerley
Robin
R
Sherrington
D002874:Chromosome Mapping; D002878:Chromosomes, Human, Pair 1 / Q000235:genetics; D002883:Chromosomes, Human, Pair 14 / Q000235:genetics; D002889:Chromosomes, Human, Pair 2 / Q000235:genetics; D002895:Chromosomes, Human, Pair 5 / Q000235:genetics; D002898:Chromosomes, Human, Pair 8 / Q000235:genetics; D015331:Cohort Studies; D003364:Costa Rica; D004247:DNA / Q000235:genetics; D005192:Family Health; D005260:Female; D015894:Genome, Human; D006720:Homozygote; D006801:Humans; D008126:Lod Score; D008297:Male; D009679:Nuclear Family; D010641:Phenotype; D012559:Schizophrenia / Q000235:genetics*; D013030:Spain / Q000208:ethnology
D004247:DNA