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John A. McGrath, MA; Dimitrios Avramopoulos, MD, PhD; Virginia K. Lasseter, BA; Paula S. Wolyniec, MA; M. Daniele Fallin, PhD; Kung-Yee Liang, PhD; Gerald Nestadt, MD; Mary H. Thornquist, PhD; James R. Luke, PsyD; Pei-Lung Chen, MD; David Valle, MD; Ann E. Pulver, ScD

Arch Gen Psychiatry. 2009;66(6):591-600.

Context  Factor analysis of the signs and symptoms of schizophrenia yields dimensional phenotypes that may relate to underlying genetic variation. Examination of familiality of factor scores can demonstrate whether they are likely to be of use in genetic research.

Objective  To produce a broader set of factorial phenotypes that are tested for familiality including core symptoms of schizophrenia and additional indicators of social, work, and educational dysfunction.

Design  The study used psychiatric assessment data collected from several large samples of individuals with schizophrenia who have participated in family or case-control genetic studies (1988-2006) in the Epidemiology-Genetics Program in Psychiatry, The Johns Hopkins University School of Medicine, Baltimore, Maryland. Seventy-three signs and symptoms were selected from direct assessment interviews and consensus diagnostic ratings (integrating interview data, medical records, and informant reports).

Setting  Study participants were recruited from across the United States, and a few additional participants were recruited from Canada, Greece, Italy, Poland, and Israel. Assessments generally were performed in the individuals' homes.

Participants  Forty-three percent of 1199 volunteers had largely white European backgrounds. The remaining individuals were recruited for family and case-control studies with focus on Ashkenazi Jews. All individuals had a consensus diagnosis of schizophrenia (including schizoaffective disorder) using DSM-III or DSM-IV criteria.

Main Outcome Measures  The 73 indicators were subjected to principal components factor analysis, and factor scores representing 9 dimensions were analyzed for familiality.

Results  The 9 factors include the often-reported delusions, hallucinations, disorganization, negative, and affective factors; novel factors included child/adolescent sociability, scholastic performance, disability/impairment, and prodromal factors. All 9 factors demonstrated significant familiality (measured by a heritability statistic), with the highest scores for disability/impairment (0.61), disorganization (0.60), and scholastic performance (0.51).

Conclusions  The factor scores show varying degrees of familiality and may prove useful as quantitative traits and covariates in linkage and association studies.

Author Affiliations: Department of Psychiatry (Mr McGrath, Drs Avramopoulos, Nestadt, Thornquist, Luke, and Pulver, and Mss Lasseter and Wolyniec), McKusick-Nathans Institute of Genetic Medicine (Drs Avramopoulos, Chen, and Valle), and Bloomberg School of Public Health (Drs Fallin, Liang, and Pulver), The Johns Hopkins University, Baltimore, Maryland.

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