Tae-Min Shin

Association analysis of COMT polymorphisms with schizophrenia and smooth pursuit eye movement abnormality.

Schizophrenia is a multifactorial disorder characterized by the contribution of multiple susceptibility genes that may act in conjunction with epigenetic processes and environmental factors. The catechol-O-methyltransferase (COMT) gene, which is located in the 22q11 microdeletion, has been considered as a candidate gene for schizophrenia because of its ability to degrade catecholamines, including dopamine. In a genetic analysis, neurophysiological endophenotype in schizophrenia, such as smooth pursuit eye movement (SPEM) disturbance, is considered to be a good trait marker, because it may be under more direct genetic control. This study was performed to examine the genetic association of COMT polymorphisms with the risk of schizophrenia and SPEM abnormality in a Korean population. Six single-nucleotide polymorphisms of COMT were genotyped by TaqMan assay. Their genetic effects on the risk of schizophrenia were analyzed in 354 patients and 396 controls using χ2 analyses. Among the schizophrenic patients, 166 subjects were selected for association analyses of COMT polymorphisms with SPEM abnormality. From the six COMT polymorphisms, rs6267 showed an association with the reduced risk of schizophrenia after correction (Pcorr = 0.02). In analysis of SPEM abnormality, no significant associations were detected with COMT polymorphisms. The results of the present study provide the evidence that in a Korean population, COMT on the 22q11 locus is likely involved in the development of schizophrenia, but not in the SPEM function abnormality.

Association of ZDHHC8 polymorphisms with smooth pursuit eye movement abnormality.

The zinc finger DHHC domain‐containing protein 8 (ZDHHC8) is located in the 22q11 microdeletion region and may contribute to the behavioral deficit associated with 22q11 deletion syndrome. Although polymorphisms of ZDHHC8 have been reported to be associated with the risk of schizophrenia, those associations are still controversial. This study was performed to validate the genetic association of ZDHHC8 polymorphisms with the risk of schizophrenia, and also to scrutinize the association with smooth pursuit eye movement (SPEM) abnormality in a Korean population. Five SNPs of ZDHHC8 were genotyped by TaqMan assay. Their genetic effects on the risk of schizophrenia were analyzed in 354 patients and 396 controls using allele‐based χ2 analyses. Association of ZDHHC8 polymorphisms with SPEM abnormality among 166 schizophrenic patients were analyzed using multiple regressions. No ZDHHC8 polymorphisms were found to be associated with the risk of schizophrenia. However, four SNPs and one haplotype (ht4) were strongly associated with the risk of SPEM abnormality even after multiple correction (P = 0.00005–0.0007, Pcorr = 0.0001–0.002). The results of the present study provide the first evidence that ZDHHC8 on the 22q11 locus might have influence on SPEM function of schizophrenia patients in a Korean population and may provide a new clue for understanding differential effects of candidate genes in schizophrenia.

Association of RANBP1 haplotype with smooth pursuit eye movement abnormality.

Schizophrenia is a multifactorial disorder and smooth pursuit eye movement (SPEM) disturbance is proposed as one of the most consistent neurophysiological endophenotype in schizophrenia. The aim of this study was to examine the genetic association of RANBP1 polymorphisms with the risk of schizophrenia and with the risk of SPEM abnormality in schizophrenia patients in a Korean population. Two SNPs of RANBP1 were genotyped by TaqMan assay. Their genetic effect of single/haplotype polymorphisms on the risk of schizophrenia and SPEM abnormality from 354 patients and 396 controls were performed using χ2 and multiple regression analyses. Although no RANBP1 polymorphisms were associated with the risk of schizophrenia, a common haplotype, RANBP1‐ht2 (rs2238798G–rs175162T), showed significant association with the risk of SPEM abnormality among schizophrenia patients after multiple correction (Pcorr = 0.002–0.0003). The results of present study provide the evidence that RANBP1 on 22q11.21 locus might be causally related to the SPEM abnormality rather than the development of schizophrenia.

Genetic association analysis of ERBB4 polymorphisms with the risk of schizophrenia and SPEM abnormality in a Korean population.

The human receptor tyrosine-protein kinase erbB-4 (ERBB4) gene mediates neuregulin 1 (NRG1) signaling, and is involved in neuronal migration and differentiation. Despite the potential significance of ERBB4 in the development of schizophrenia, relatively few genetic studies for the association of ERBB4 with schizophrenia were performed in the populations including Ashkenazi Jews, Americans including Caucasians and African Americans, and Han Chinese. In this study, differences in ERBB4 variations were investigated to determine association with schizophrenia and smooth pursuit eye movement (SPEM) abnormality in a Korean population. Seven polymorphisms in ERBB4 gene were genotyped in 435 schizophrenia cases and 390 unrelated healthy controls. In order to investigate the relationship between ERBB4 and the risk of schizophrenia and SPEM abnormality, differences in SNP and haplotype distribution were analyzed using logistic and multiple regression analyses. However, we failed to replicate the associations reported by previous studies in other populations. Although statistically not significant, the tendency towards associations between ERBB4 polymorphisms and the risk of schizophrenia and SPEM abnormality in this study from a Korean population would be helpful for further genetic etiology studies in schizophrenia.

Genetic association analysis of CNR1 and CNR2 polymorphisms with schizophrenia in a Korean population.

Located on 6q15 and 1p36.11, cannabinoid receptor 1 (CNR1) and cannabinoid receptor 2 (CNR2) genes are considered to be a positional and functional candidate gene for the development of mental disorders such as schizophrenia because CNR1 is known as a regulator of dopamine signaling in the hippocampus and the cerebral cortex. However, few genetic studies have been carried out to investigate an association of CNR1 and CNR2 polymorphisms and the risk of schizophrenia. In this study, although the result indicates that CNR1 and CNR2 variations are unlikely to influence schizophrenia susceptibility in a Korean population, the findings would provide meaningful information for further genetic studies.

Neuregulin 3 does not confer risk for schizophrenia and smooth pursuit eye movement abnormality in a Korean population

Located on chromosome 10q22‐q23, the human neuregulin3 (NRG3) is considered to be a strong positional and functional candidate gene for schizophrenia pathogenesis. Several case–control studies examining the association of polymorphisms in NRG3 with schizophrenia and/or related traits such as delusion have been reported recently in cohorts of Han Chinese, Ashkenazi Jews, Australians and white Americans of Western European ancestry. Thus, this study aimed to comprehensively investigate the association of NRG3 genetic variations with the risk of schizophrenia and smooth pursuit eye movement (SPEM) abnormality in a Korean population. Using TaqMan assay, six single‐nucleotide polymorphisms (SNPs) in the intronic region of NRG3 were genotyped and two major haplotypes were identified in 435 patients with schizophrenia as cases and 393 unrelated healthy individuals as controls. A total of 113 schizophrenia patients underwent an eye tracking task, and degree of SPEM abnormality was measured using the logarithmic values of the signal/noise (Ln S/N) ratio. Differences in frequency distributions were analyzed using logistic and regression models following various modes of genetic inheritance and controlling for age and sex as covariates. Subsequent analysis revealed that the frequency distributions of NRG3 polymorphisms and haplotypes were similar between schizophrenia patients and healthy controls of Korean ethnicity. Furthermore, no significant differences were observed between the genetic variants tested for SPEM abnormality. By elucidating a lack of association in a Korean population, findings from this study may contribute to the understanding of the genetic etiology focusing on the role of NRG3 in schizophrenia pathogenesis.

Erratum to: Lack of Associations of Neuregulin 1 Variations with Schizophrenia and Smooth Pursuit Eye Movement Abnormality in a Korean Population

Schizophrenia is a serious and disabling mental disorder with a high heritability rate. The human neuregulin 1 (NRG1) on 8p12 has been implicated as a candidate gene for schizophrenia. However, controversial results of the associations of NRG1 polymorphisms with schizophrenia and related phenotypes have been reported. In this study, four NRG1 single nucleotide polymorphisms, three in the promoter region, and one nonsynonymous in coding region, were genotyped in a total of 825 subject including 435 schizophrenia cases and 390 normal controls of Korean ethnicity. Although logistic association analysis of NRG1 polymorphisms and haplotypes with schizophrenia showed a nominal association in rs4623364G > C (P = 0.04), the significance disappeared after corrections for multiple testing (corrected P > 0.05). Additional case/control and multiple regression analyses in schizophrenia patients using a method that measures the smooth pursuit eye movement (SPEM) function globally based on natural logarithmic values of the signal/noise ratio also showed no association between NRG1 variants and SPEM abnormality among patients with schizophrenia (P > 0.05). Despite the need for further replications in other cohorts, our findings provide additional supporting information that four variants in NRG1 investigated in this study may not be associated with schizophrenia and its related SPEM function in a Korean population.

Lack of association between DISC1 polymorphisms and risk of schizophrenia in a Korean population

The DISC1 gene is considered to be a strong candidate gene for the development of schizophrenia. This study examines the association of DISC1 polymorphisms with schizophrenia in a Korean population. Although we fail to discover convincing evidence that DISC1 affects schizophrenia development, our findings may be useful for further genetic studies.

Lack of association of the RTN4R genetic variations with risk of schizophrenia and SPEM abnormality in a Korean population.

This study examined the association of the reticulon 4 receptor (RTN4R) gene with schizophrenia and smooth pursuit eye movement (SPEM) abnormality in a Korean population. Although we failed to provide convincing evidence that RTN4R is associated with schizophrenia development and SPEM impairment, our findings may be useful for further genetic studies.

Biomechanical Evaluation for Washing Machine Design Suggested Newly for Prevention of Musculoskeletal Disorders

Recently, many studies have reported the fact that an excessively accumulated psychological and physical burden induced from physical labor conducted routinely in home and industry can be one of main reasons of musculoskeletal disorders in the working population. This fact makes increase interests in studies to reduce a risk of musculoskeletal disorders through grafting ergonomic considerations on working environment. However, there are currently limited methodologies in quantitative evaluations of new ergonomic suggestions to reduce a risk of musculoskeletal disorders. The current study is therefore performed to evaluate quantitatively effects of a design of washing machine as a new ergonomic suggestion onto prevention of musculoskeletal disorders, through application of a biomechanical evaluation methodology. For this, three-dimensional motion analysis by using musculoskeletal models with Rapid Entire Body Assessment (REBA), which has been generally used for a simple evaluation of a degree of harmfulness of the human body at specific working postures to be considered, was performed. The results of REBA did not give us enough information and their results were somewhat simple and inaccurate, but the results of the three-dimensional motion analysis give us enough information such as alteration of main muscle forces and joint moments required during washing work. All results showed that the main muscle strengths and joint moments were decreased effectively for reduction of a risk of musculoskeletal disorders during the washing work with newly designed washing machine evaluated in the current study, compared with those generated during the washing work with general washing machine. From these results, it can be concluded that a risk of the musculoskeletal disorders, which may be induced by a repetitive washing work, may be reduced through using the washing machine designed ergonomically and newly. Also, it is thought that if our ergonomic design can be applied for improvement of working environment in lifting and laying works conducted repeatedly for a treatment work of goods, which have a strong resemblance to the behaviors generated * 이 저서(논문·예술연구)는 2001학년도 연세대학교 학술연구비의 (부분적인) 지원에 의하여 이루어진 것임.