Genome scan of Han Chinese schizophrenia families from Taiwan: confirmation of linkage to 10q22.3.

OBJECTIVE: Genome-wide linkage analyses of schizophrenia have identified several regions that may harbor schizophrenia susceptibility genes, but given the complex etiology of the disorder, it is unlikely that all susceptibility regions have been detected. To address this issue, the authors ascertained 606 Han Chinese families comprising 1,234 affected members. METHOD: Probands with schizophrenia were recruited from six data collection field research centers in Taiwan. Each proband underwent a diagnostic screen with supplemental medical records and a semistructured interview. Following this screen, the authors administered the Mandarin Chinese version of the Diagnostic Interview for Genetic Studies. Best-estimate final diagnoses were made by two board-certified psychiatrists. The genotyping was conducted by the Center for Inherited Disease Research, with 386 markers spaced at an average of 9-centimorgan (cM) intervals. Empirical simulations were generated to determine genome-wide significance. RESULTS: The authors found five regions with nonparametric linkage z scores 2.0 or greater. These were the following: 2.08 was reached for D1S551 (113.7) cM at 1p31.1 and 2.31 for D2S410 (125.2 cM) at 2q14.1; 2.00 was reached for D4S2361 (93.5 cM) at 4q21.23, and 2.07 for D15S1012 (36 cM) at 15q14, the largest nonparametric linkage z score was 2.88 for D10S2327 (100.92 cM) at 10q22.3. CONCLUSIONS: Our 10q22.3 finding at 100.9 cM is consistent with a previously reported nonparametric linkage score of 4.27 at 107.2 cM on chromosome 10, although it did not attain genome-wide significance in this study.

Absence of significant associations between four AKT1 SNP markers and schizophrenia in the Taiwanese population.

AKT1 (V-akt murine thymoma viral oncogene homolog 1) is a protein kinase isoform of AKT. Five single-nucleotide polymorphisms, rs3803300, rs1130214, rs3730358, rs2498799 and rs2494732, at the genomic region of AKT1 have been reported to be significantly associated with schizophrenia. We tested for the presence of these five single-nucleotide polymorphisms in a Taiwanese population by genotyping 218 co-affected schizophrenia families. Both single locus and haplotypes analyses showed no association of these single-nucleotide polymorphisms with schizophrenia. These findings fail to support AKT1 as a susceptibility gene for schizophrenia in the Taiwanese population.

Taiwan schizophrenia linkage study: the field study.

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.