Finding Suitable Phenotypes for Genetic Studies of Schizophrenia: Heritability and Segregation Analysis

• Published in: Biological psychiatry (1969) Vol. 64; no. 2; pp. 128 - 136
• Main Authors: Aukes, Maartje F., Alizadeh, Behrooz Z., Sitskoorn, Margriet M., Selten, Jean-Paul, Sinke, Richard J., Kemner, Chantal, Ophoff, Roel A., Kahn, René S.
• Format: Journal Article
• Language: English
• Published: New York, NY Elsevier Inc 15.07.2008; Elsevier Science
• Subjects: Adult; Adult and adolescent clinical studies; Alleles; Biological and medical sciences; Female; Genes, Dominant; Genetic Markers - genetics; Genotype; Heritability; Humans; inheritance pattern; Male; Medical sciences; Middle Aged; Multigene Family - genetics; neurocognition; Neuropsychological Tests; Pedigree; personality; Personality Tests; Phenotype; Psychiatric Status Rating Scales; Psychiatric/Mental Health; Psychology. Psychoanalysis. Psychiatry; Psychopathology. Psychiatry; psychophysiology; Psychoses; Psychotic Disorders - diagnosis; Psychotic Disorders - genetics; Psychotic Disorders - psychology; quantitative trait; Quantitative Trait Loci - genetics; Schizophrenia; Schizophrenia - diagnosis; Schizophrenia - genetics; Schizophrenic Psychology; Social Environment; neurocognition; personality; quantitative trait; Heritability; psychophysiology; schizophrenia; inheritance pattern; Segregation; Schizophrenia; Cognition; Personality; Genetic determinism; Psychosis; Phenotype; Genetics; Psychophysiology
• ISSN: 0006-3223; 1873-2402; 1873-2402
• DOI: 10.1016/j.biopsych.2007.12.013

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. 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. 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. 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.