Objective: Previous research on autism spectrum disorder (ASD) in Koreans has primarily focused on genetic diversity because of its high heritability. However, the emerging recognition of transgenerational epigenetic changes has recently shifted research attention towards epigenetic perspectives. Methods: This study investigated the DNA methylation patterns of the promoter regions of candidate genes such asNR3C1, ASCL1, and FOXO3 in blood samples from ASD probands and their unaffected siblings. The analysis included 54 families (ASD proband group: 54; unaffected biological sibling group: 63). The diagnostic process involved screening the probands and their siblings for ASD based on the Diagnostic and Statistical Manual of Mental Disorders 5th edition.Intelligence, social ability, and medical history were thoroughly assessed using various scales and questionnaires.Genomic DNA from blood samples was analyzed using a methylation-sensitive quantitative polymerase chain reaction to examine the DNA methylation status of candidate genes. Results: Methylation levels in candidate gene promoter regions differed significantly between the proband and sibling groups for all candidate genes. Correlation analysis between the proband and sibling groups revealed strong and significant correlations in NR3C1 and ASCL1 methylation. Additionally, in the analysis of the relationship between DNA and ASD phenotypes, FOXO3 methylation correlated with social quotient in probands, and ASCL1 methylation was associated with nonverbal communication, and daily living skills as measured by the Korean Vineland Adaptive Behavior Scale. Notably, ASCL1 methylation was significantly associated with parental age at pregnancy. Conclusion This study proposes DNA methylation of NR3C1, ASCL1, and FOXO3 in peripheral blood samples is a potential epigenetic biomarker of ASD.

Objective: Previous research on autism spectrum disorder (ASD) in Koreans has primarily focused on genetic diversity because of its high heritability. However, the emerging recognition of transgenerational epigenetic changes has recently shifted research attention towards epigenetic perspectives. Methods: This study investigated the DNA methylation patterns of the promoter regions of candidate genes such asNR3C1, ASCL1, and FOXO3 in blood samples from ASD probands and their unaffected siblings. The analysis included 54 families (ASD proband group: 54; unaffected biological sibling group: 63). The diagnostic process involved screening the probands and their siblings for ASD based on the Diagnostic and Statistical Manual of Mental Disorders 5th edition.Intelligence, social ability, and medical history were thoroughly assessed using various scales and questionnaires.Genomic DNA from blood samples was analyzed using a methylation-sensitive quantitative polymerase chain reaction to examine the DNA methylation status of candidate genes. Results: Methylation levels in candidate gene promoter regions differed significantly between the proband and sibling groups for all candidate genes. Correlation analysis between the proband and sibling groups revealed strong and significant correlations in NR3C1 and ASCL1 methylation. Additionally, in the analysis of the relationship between DNA and ASD phenotypes, FOXO3 methylation correlated with social quotient in probands, and ASCL1 methylation was associated with nonverbal communication, and daily living skills as measured by the Korean Vineland Adaptive Behavior Scale. Notably, ASCL1 methylation was significantly associated with parental age at pregnancy. Conclusion This study proposes DNA methylation of NR3C1, ASCL1, and FOXO3 in peripheral blood samples is a potential epigenetic biomarker of ASD.

Objective: Previous research on autism spectrum disorder (ASD) in Koreans has primarily focused on genetic diversity because of its high heritability. However, the emerging recognition of transgenerational epigenetic changes has recently shifted research attention towards epigenetic perspectives. Methods: This study investigated the DNA methylation patterns of the promoter regions of candidate genes such asNR3C1, ASCL1, and FOXO3 in blood samples from ASD probands and their unaffected siblings. The analysis included 54 families (ASD proband group: 54; unaffected biological sibling group: 63). The diagnostic process involved screening the probands and their siblings for ASD based on the Diagnostic and Statistical Manual of Mental Disorders 5th edition.Intelligence, social ability, and medical history were thoroughly assessed using various scales and questionnaires.Genomic DNA from blood samples was analyzed using a methylation-sensitive quantitative polymerase chain reaction to examine the DNA methylation status of candidate genes. Results: Methylation levels in candidate gene promoter regions differed significantly between the proband and sibling groups for all candidate genes. Correlation analysis between the proband and sibling groups revealed strong and significant correlations in NR3C1 and ASCL1 methylation. Additionally, in the analysis of the relationship between DNA and ASD phenotypes, FOXO3 methylation correlated with social quotient in probands, and ASCL1 methylation was associated with nonverbal communication, and daily living skills as measured by the Korean Vineland Adaptive Behavior Scale. Notably, ASCL1 methylation was significantly associated with parental age at pregnancy. Conclusion This study proposes DNA methylation of NR3C1, ASCL1, and FOXO3 in peripheral blood samples is a potential epigenetic biomarker of ASD.

Objective: Previous research on autism spectrum disorder (ASD) in Koreans has primarily focused on genetic diversity because of its high heritability. However, the emerging recognition of transgenerational epigenetic changes has recently shifted research attention towards epigenetic perspectives. Methods: This study investigated the DNA methylation patterns of the promoter regions of candidate genes such asNR3C1, ASCL1, and FOXO3 in blood samples from ASD probands and their unaffected siblings. The analysis included 54 families (ASD proband group: 54; unaffected biological sibling group: 63). The diagnostic process involved screening the probands and their siblings for ASD based on the Diagnostic and Statistical Manual of Mental Disorders 5th edition.Intelligence, social ability, and medical history were thoroughly assessed using various scales and questionnaires.Genomic DNA from blood samples was analyzed using a methylation-sensitive quantitative polymerase chain reaction to examine the DNA methylation status of candidate genes. Results: Methylation levels in candidate gene promoter regions differed significantly between the proband and sibling groups for all candidate genes. Correlation analysis between the proband and sibling groups revealed strong and significant correlations in NR3C1 and ASCL1 methylation. Additionally, in the analysis of the relationship between DNA and ASD phenotypes, FOXO3 methylation correlated with social quotient in probands, and ASCL1 methylation was associated with nonverbal communication, and daily living skills as measured by the Korean Vineland Adaptive Behavior Scale. Notably, ASCL1 methylation was significantly associated with parental age at pregnancy. Conclusion This study proposes DNA methylation of NR3C1, ASCL1, and FOXO3 in peripheral blood samples is a potential epigenetic biomarker of ASD.

Background: To overcome the limitations of relying on data from a single institution, many researchers have studied data linkage methodologies. Data linkage includes errors owing to legal issues surrounding personal information and technical issues related to data processing. Linkage errors affect selection bias, and external and internal validity. Therefore, quality verification for each connection method with adherence to personal information protection is an important issue. This study evaluated the linkage quality of linked data and analyzed the potential bias resulting from linkage errors. Methods: This study analyzed claims data submitted to the Health Insurance Review and Assessment Service (HIRA DATA). The linkage errors of the two deterministic linkage methods were evaluated based on the use of the match key. The first deterministic linkage uses a unique identification number, and the second deterministic linkage uses the name, gender, and date of birth as a set of partial identifiers. The linkage error included in this deterministic linkage method was compared with the absolute standardized difference (ASD) of Cohen’s according to the baseline characteristics, and the linkage quality was evaluated through the following indicators: linked rate, false match rate, missed match rate, positive predictive value, sensitivity, specificity, and F1-score. Results: For the deterministic linkage method that used the name, gender, and date of birth as a set of partial identifiers, the true match rate was 83.5 and the missed match rate was 16.5.Although there was bias in some characteristics of the data, most of the ASD values were less than 0.1, with no case greater than 0.5. Therefore, it is difficult to determine whether linked data constructed with deterministic linkages have substantial differences. Conclusion This study confirms the possibility of building health and medical data at the national level as the first data linkage quality verification study using big data from the HIRA. Analyzing the quality of linkages is crucial for comprehending linkage errors and generating reliable analytical outcomes. Linkers should increase the reliability of linked data by providing linkage error-related information to researchers. The results of this study will serve as reference data to increase the reliability of multicenter data linkage studies.

Objectives: This study examined the changes in anxiety and depressive symptoms in the parents of Korean adults with autism spectrum disorder (ASD) after participating in the Korean version of the Program for the Education and Enrichment of Relational Skills for Young Adults (PEERS ® -YA-K). Methods: Forty-six parents were enrolled (mean age 54.7 years; 22 fathers and 24 mothers), of whom 27 participated in the PEERS ® -YA-K as social coaches. Participants completed self-report scales, including the Test of Young Adult Social Skills Knowledge (TYASSK), Beck Depression Inventory (BDI), Beck Anxiety Inventory (BAI), and Symptom Check-List-90-R (SCL-90-R). The scales were administered three times: before and after the 16-week program and 4 months after the program ended. Differences between participant variables at pretreatment, post-treatment, and follow-up were analyzed using paired-sample t-tests. Results: Participants showed a significant improvement in their social skills knowledge (TYASSK) (:p<0.01). There was a significant improvement in the BAI and BDI scores of parents with severe depressive and anxiety symptoms at the baseline (p<0.05). Paternal paranoia and maternal hostility results also significantly improved on the SCL-90-R. Conclusion This study suggests that PEERS ® -YA-K can reduce parental anxiety and depressive symptoms. To the best of our knowledge, this is the first to compare the degree of depression and anxiety after PEERS ® -YA-K in parents of adults with ASD.

Objectives: Sleep is fundamental to maintaining homeostatic control and has behavioral and psychological effects on humans. To better understand the function and pathophysiology of sleep, specific gene expressions in reference to sleep deprivation have been studied. In this study, we investigated the gene expression of peripheral blood mononuclear cells after sleep deprivation to better understand the functional consequence of sleep. Methods: In eight healthy men, 24 h sleep deprivation was induced. Blood was sampled at 14:00, before and after sleep deprivation.mRNA was isolated and analyzed via microarrays. cDNAs before and after sleep deprivation were coupled to Cy3 or Cy5, respectively, and normalized cDNAs were selected with a ratio greater than two as a significant gene. Results are expressed as mean. Results: Among 41174 transcripts, 38852 genes were selected as reliable, and only a small minority (< 1%) of the genes were up-or down-regulated. Total six and eleven genes were selected as significant upregulated and downregulated genes, respectively. Protein tyrosine phosphatase receptor type O was most upregulated (6.9-fold), and low-density lipoprotein receptor-related protein 5-like protein showed the most substantial inhibition (0.06-fold). Conclusions This study showed significant associations between sleep deprivation and the immune system. Acute sleep deprivation affects pathways in proinflammatory cytokines as well as metabolic pathways of glutamate and purine, neurotransmitters related to sleep and wake cycle.

Objective: This study aimed to examine the validity of the Korean version of the Autism Diagnostic Interview-Revised (K-ADI-R) and determine its efficacy in identifying individuals with autism spectrum disorder (ASD). Methods: Data were pooled from several past and ongoing studies as well as clinical records acquired at Seoul National University Bundang Hospital from 2008 to 2017. The K-ADI-R were administered and scored by trained research reliable examiners. Measurements to investigate the validity of the K-ADI-R was through sensitivity, specificity, positive predictive values (PPV), negative predictive values (NPV), and Cohen’s kappa. Results: A total of 1,271 (age 88.9±62.42 months, male=927) participants were included. The K-ADI-R yielded strong psychometric properties with high sensitivity (86.06–99.27%), specificity (84.75–99.55%), PPV (92.33–99.72%), and NPV (79.43–98.64%). There were significant differences in item scores across the K-ADI-R diagnostic algorithm regardless of age and sex (p<0.001). Agreement between the K-ADI-R and other ASD related measurements ranged between levels of good to excellent. Conclusion Despite language or cultural boundaries, the K-ADI-R demonstrated high levels of sensitivity, specificity, PPV, and NPV within a wide range of participants; hence, suggesting promising usage as a valuable diagnostic instrument for individuals with ASD.

Objective: This cross-cultural study aims to examine the psychometric properties of the Social Responsiveness Scale (SRS) and to determine the best-estimate-cut-off scores for the diagnosis of autism spectrum disorder (ASD) in Korean preschool children. Methods: A total of 563 children was recruited from multiple sources, including Seoul National University Bundang Hospital. Participants were assessed by a multidisciplinary research team using multiple diagnostic tools based on DSM-5 diagnostic criteria. Discriminative validity was tested by comparing the difference in SRS scores between ASD and non-ASD groups. Convergent validity was tested by examining correlations between SRS scores with other diagnostic instruments. A receiver operation characteristic curve analysis was conducted to test the sensitivity and specificity of SRS and to determine the best-estimate-cut-off scores for screening ASD in Korean preschool children. Results: There were significant differences in the total SRS scores between the ASD (n=242) and non-ASD group (n=321) (p<0.01, 95% confidence interval [CI]: 14.08–17.24). The differences were significant even after adjusting for age. SRS scores were significantly correlated with other prescreening diagnostic tools for ASD. The best-estimate cut-off score to screen ASD was 55 (area under curve=0.88, sensitivity 78.1%, specificity 86.6%). Conclusion The SRS is a valid and reliable instrument to screen and aid in the diagnosis of ASD in Korean preschool children. The adjusted cut-off scores, notably lower than in the original U.S. version, may yield a more accurate diagnosis by reflecting transcultural differences.

Objective: This study aimed to examine the validity of the Korean version of the Autism Diagnostic Interview-Revised (K-ADI-R) and determine its efficacy in identifying individuals with autism spectrum disorder (ASD). Methods: Data were pooled from several past and ongoing studies as well as clinical records acquired at Seoul National University Bundang Hospital from 2008 to 2017. The K-ADI-R were administered and scored by trained research reliable examiners. Measurements to investigate the validity of the K-ADI-R was through sensitivity, specificity, positive predictive values (PPV), negative predictive values (NPV), and Cohen’s kappa. Results: A total of 1,271 (age 88.9±62.42 months, male=927) participants were included. The K-ADI-R yielded strong psychometric properties with high sensitivity (86.06–99.27%), specificity (84.75–99.55%), PPV (92.33–99.72%), and NPV (79.43–98.64%). There were significant differences in item scores across the K-ADI-R diagnostic algorithm regardless of age and sex (p<0.001). Agreement between the K-ADI-R and other ASD related measurements ranged between levels of good to excellent. Conclusion Despite language or cultural boundaries, the K-ADI-R demonstrated high levels of sensitivity, specificity, PPV, and NPV within a wide range of participants; hence, suggesting promising usage as a valuable diagnostic instrument for individuals with ASD.