Heritability and number of quantitative trait loci of neurocognitive functions in families with schizophrenia.
Despite evidence for several chromosomal loci linked to schizophrenia, no susceptibility genes have been identified for the disorder. Using quantitative measures of phenotypic affection in place of clinical diagnostic categories or dichotomous classification of the affection status may be more effective in searching for susceptibility genes. Neurocognitive traits have been suggested as putative quantitative endophenotypes of the disorder, but their heritability estimates are not well known. We investigated the heritability of working memory, verbal declarative memory and its different components, and both verbal and visual ability functions in schizophrenia families with a well-ascertained pedigree structure. We also estimated the number of quantitative trait loci (QTLs) contributing to these neurocognitive functions. Additive genetic heritability of the neurocognitive functions was estimated in a sample of schizophrenia patients and their first-degree relatives (N = 264) from an isolated geographical subregion in Finland. The number of QTLs was analyzed using Markov chain Monte Carlo segregation analysis. Significant heritabilities were found in working memory and ability functions. Furthermore, the working memory functions revealed the most restricted number of QTLs. The mean numbers of loci for verbal and visual working memory were 1.2 and 1.0, respectively, with corresponding posterior probabilities of 73% and 70% for at least one locus. In declarative memory variables, the number of loci was more dispersed. Our results suggest that neurocognitive measures, particularly working memory, may provide valid quantitative phenotypic traits for linkage analyses searching predisposing genes for schizophrenia.
Department of Mental Health and Alcohol Research, National Public Health Institute of Finland, Helsinki. annamari.tuulio-henriksson@ktl.fi
Annamari
A
Tuulio-Henriksson
Jari
J
Haukka
Timo
T
Partonen
Teppo
T
Varilo
Tiina
T
Paunio
Jesper
J
Ekelund
Tyrone D
TD
Cannon
Joanne M
JM
Meyer
Jouko
J
Lönnqvist
D000328:Adult; D003071:Cognition / Q000502:physiology*; D005192:Family Health; D005260:Female; D006801:Humans; D008297:Male; D008390:Markov Chains; D008875:Middle Aged; D008957:Models, Genetic; D009010:Monte Carlo Method; D009483:Neuropsychological Tests; D019655:Quantitative Trait, Heritable; D012559:Schizophrenia / Q000235:genetics* / Q000503:physiopathology; D012565:Schizophrenic Psychology