Finding suitable phenotypes for genetic studies of schizophrenia: heritability and segregation analysis.
BACKGROUND
Schizophrenia is a highly heritable and complex disorder. Multiple genes are likely to be involved, complicating genetic research into the etiology of this disorder. Intermediate phenotypes or endophenotypes may facilitate genetic research if they display a simpler mode of transmission than schizophrenia itself, i.e., if they reflect more closely the underlying genetic effects.


METHODS
Twenty-five multigenerational families with multiple members affected with schizophrenia (180 subjects) were administered an extensive neuropsychological, psychophysiological, and personality test battery. Familial correlations were calculated to select heritable traits. Subsequent heritability analysis followed by commingling and segregation analysis were performed to unravel the pattern of transmission and to estimate heritability.


RESULTS
Five traits, including sensorimotor gating, openness, verbal fluency, early visual perception, and spatial working memory, showed moderate familial correlations. Heritability estimates for these traits ranged from 37% to 54%. A major gene model resembling dominant transmission was found for both sensorimotor gating and openness. Verbal fluency, early visual perception, and spatial working memory may be accounted for by polygenic, multifactorial, or environmental effects.


CONCLUSIONS
Only 2 of 13 candidate endophenotypes showed a simple mode of transmission useful for successful application in molecular genetic research: sensorimotor gating and openness. To our knowledge, this is the first study to investigate the pattern of transmission for these traits.
Aukes
Maartje F
MF
Department of Psychiatry, Rudolf Magnus Institute of Neuroscience, University Medical Center Utrecht, Utrecht, the Netherlands. M.Aukes@umcutrecht.nl
Alizadeh
Behrooz Z
BZ
Sitskoorn
Margriet M
MM
Selten
Jean-Paul
JP
Sinke
Richard J
RJ
Kemner
Chantal
C
Ophoff
Roel A
RA
Kahn
René S
RS
D000328:Adult; D000483:Alleles; D005260:Female; D005799:Genes, Dominant; D005819:Genetic Markers / Q000235:genetics; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D005810:Multigene Family / Q000235:genetics*; D009483:Neuropsychological Tests; D010375:Pedigree; D010556:Personality Tests; D010641:Phenotype; D011569:Psychiatric Status Rating Scales; D011618:Psychotic Disorders / Q000175:diagnosis / Q000235:genetics* / Q000523:psychology; D040641:Quantitative Trait Loci / Q000235:genetics; D012559:Schizophrenia / Q000175:diagnosis / Q000235:genetics*; D012565:Schizophrenic Psychology; D012931:Social Environment
D005819:Genetic Markers