title: Genome-wide linkage scan of quantitative traits representing symptom dimensions in multiplex schizophrenia families.
abstract: Symptom dimensions of schizophrenia are likely to be the intermediate phenotypes under the control of disease-susceptibility genes, or separate traits related to disease-modifier genes. This study aimed to identify chromosomal loci linked to symptom dimensions of schizophrenia through genome-wide quantitative trait locus (QTL) linkage analysis. The study subjects consisted of 56 families with 183 members including 123 affected individuals. Symptom evaluations were performed on lifetime basis. Through principal component factor analysis, eight quantitative phenotypes representing symptom dimensions were identified. Genotyping was done for 6008 SNP markers, and genome-wide QTL linkage analysis was performed. No symptom dimension showed a significant linkage attaining genome-wide empirical thresholds. We observed seven regions yielding linkage signals attaining genome-wide empirical thresholds for suggestive linkage (NPL Z score = 2.78-3.49); chromosome 15q26.1 for 'non-paranoid delusion factor', 2p24.3 and 7q31.1 for 'prodromal impairment factor', 1q32.1, 9p21.3, and 9q31.2 for 'negative symptom factor', and 10p13 for 'disorganization factor'. Among these loci, chromosome 2p24.3 and 1q32.1 overlap with susceptibility loci of schizophrenia identified in our previous linkage studies. This study suggests the existence of genetic loci related to various clinical features of schizophrenia. Further genetic analyses for these dimensional phenotypes are warranted.
authors.affiliation: Department of Psychiatry, Sungkyunkwan University School of Medicine, Samsung Medical Center, Seoul, Republic of Korea.
authors.forename: Seunghyong
authors.initials: S
authors.lastname: Ryu
authors.forename: Hong-Hee
authors.initials: HH
authors.lastname: Won
authors.forename: Sohee
authors.initials: S
authors.lastname: Oh
authors.forename: Jong-Won
authors.initials: JW
authors.lastname: Kim
authors.forename: Taesung
authors.initials: T
authors.lastname: Park
authors.forename: Eun-Young
authors.initials: EY
authors.lastname: Cho
authors.forename: Youngah
authors.initials: Y
authors.lastname: Cho
authors.forename: Dong Yeon
authors.initials: DY
authors.lastname: Park
authors.forename: Yu-Sang
authors.initials: YS
authors.lastname: Lee
authors.forename: Jun Soo
authors.initials: JS
authors.lastname: Kwon
authors.forename: Kyung Sue
authors.initials: KS
authors.lastname: Hong
mesh_terms: D044466:Asian People / Q000235:genetics*; D005190:Family; D005260:Female; D008040:Genetic Linkage / Q000235:genetics*; D056426:Genetic Loci; D020022:Genetic Predisposition to Disease / Q000208:ethnology*; D005820:Genetic Testing; D055106:Genome-Wide Association Study / Q000379:methods*; D005838:Genotype; D006801:Humans; D008297:Male; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D040641:Quantitative Trait Loci / Q000235:genetics*; D056910:Republic of Korea; D012189:Retrospective Studies; D012559:Schizophrenia / Q000208:ethnology / Q000235:genetics*
keywords: Factor analysis; Linkage analysis; Quantitative traits; Schizophrenia; Symptom dimensions