Taiwan schizophrenia linkage study: The field study

Abstract

One possible reason of the inconsistent results of linkage analyses of schizophrenia, a complex disorder, was mainly due to the small sample size of studies. This Taiwan Schizophrenia Linkage Study (TSLS) was designed to collect a large family sample with at least two affected siblings of a single ethnicity. The 17.6 millions of Taiwanese Chinese, age over 15, was the sample population, and 78 psychiatric hospitals or health centers participated in this TSLS program. Before data collection started, every study subject signed the informed consent. The ascertainment protocol for data collection included blood sample, structured Diagnostic Interview for Genetic Studies (DIGS), Structured Interview for Schizotypy (SIS), scales for assessment of positive and negative symptoms (SAPS, SANS), and continuous performance test (CPT), Wisconsin card sort test (WCST) of neuropsychological functions. We have contacted 831 families for this study and 607 families, comprised 2,490 subjects, were successfully recruited. The recruitment rate was 38.4% from the estimated total of 1,582 families with at least two affected siblings. These collected family samples were fairly evenly distributed all over Taiwan. Those 2,490 study subjects (1,283 male, 1,117 female) comprised 1,568 siblings (mean age 35.7 years old) and 922 parents (mean age 63.6 years old). Of these 1,568 siblings, 1,258 (80.2%) were affected (male 795, female 463), and the mean age of onset was 22.6 years old. Among 922 parents, 65 were affected (male 14, female 51) and the age of onset was 33.1 years old. This TSLS demonstrated a successful establishment of an efficient research infrastructure to collect a large nation-wise sample of schizophrenic family for genetic linkage study.

Family-based association testing strongly implicates DRD2 as a risk gene for schizophrenia in Han Chinese from Taiwan

“…A detailed description of ascertainment and clinical assessment methods for this study is given by Hwu et al 8 Briefly, probands were recruited from six data-collection field-research centers throughout Taiwan. To be included in the study, the family was required to be of Han Chinese ancestry and to meet the entry criteria adopted by the US National Institute of Mental Health's Schizophrenia Genetics Initiative; that is, the family had to have two siblings with schizophrenia or schizoaffective disorder, depressed type (which family studies suggest may be an alternate expression of schizophrenia susceptibility genes 9 ).…”

More evidence supports the association of PPP3CC with schizophrenia

“…All genomic DNA samples were collected from the family subjects with at least two affected siblings after written informed consents had been obtained. The subjects were recruited from two research programs: the Multidimensional Psychopathology Study of Schizophrenia (MPSS) 27 from 1993 to 2001 and the Taiwan Schizophrenia Linkage Study (TSLS) 28,29 from 1998 to 2002. The 86 families of the MPSS subjects were interviewed by the research psychiatrists using the Psychiatrist Diagnostic Assessment (PDA).…”

Extended Bayesian Model Averaging in Generalized Linear Mixed Models Applied to Schizophrenia Family Data

“…The Taiwan Schizophrenia Linkage Study (TSLS) (Hwu et al, 2005), conducted from 1998 to 2002, collected a large sample of 607 Taiwanese Han Chinese families, each with at least one schizophrenic subject. These singleton or multiplex sschizophrenia families were recruited from all hospitals in Taiwan except two institutions, the Department of Psychiatry in National Taiwan University Hospital and the Universityaffiliated Taoyuan Psychiatric Center.…”

“…The second part included information on 76 SNPs on chromosome 10q22.1. The objective of TSLS in Hwu et al (2005) was to construct a linkage analysis; however, in the following, we illustrate the proposed EBMA approach, permutation test procedure, and GEE method for a family-based association study.…”