An ensemble-based likelihood ratio approach for family-based genomic risk prediction / 浙江大学学报（英文版）（B辑：生物医学和生物技术）

OBJECTIVE@#As one of the most popular designs used in genetic research, family-based design has been well recognized for its advantages, such as robustness against population stratification and admixture. With vast amounts of genetic data collected from family-based studies, there is a great interest in studying the role of genetic markers from the aspect of risk prediction. This study aims to develop a new statistical approach for family-based risk prediction analysis with an improved prediction accuracy compared with existing methods based on family history.@*METHODS@#In this study, we propose an ensemble-based likelihood ratio (ELR) approach, Fam-ELR, for family-based genomic risk prediction. Fam-ELR incorporates a clustered receiver operating characteristic (ROC) curve method to consider correlations among family samples, and uses a computationally efficient tree-assembling procedure for variable selection and model building.@*RESULTS@#Through simulations, Fam-ELR shows its robustness in various underlying disease models and pedigree structures, and attains better performance than two existing family-based risk prediction methods. In a real-data application to a family-based genome-wide dataset of conduct disorder, Fam-ELR demonstrates its ability to integrate potential risk predictors and interactions into the model for improved accuracy, especially on a genome-wide level.@*CONCLUSIONS@#By comparing existing approaches, such as genetic risk-score approach, Fam-ELR has the capacity of incorporating genetic variants with small or moderate marginal effects and their interactions into an improved risk prediction model. Therefore, it is a robust and useful approach for high-dimensional family-based risk prediction, especially on complex disease with unknown or less known disease etiology.

Genome-Wide Analysis Reveals Four Novel Loci for Attention-Deficit Hyperactivity Disorder in Korean Youths

OBJECTIVES: The molecular mechanisms underlying attention-deficit hyperactivity disorder (ADHD) remain unclear. Therefore, this study aimed to identify the genetic susceptibility loci for ADHD in Korean children with ADHD. We performed a case-control and a family-based genome-wide association study (GWAS), as well as genome-wide quantitative trait locus (QTL) analyses, for two symptom traits. METHODS: A total of 135 subjects (71 cases and 64 controls), for the case-control analysis, and 54 subjects (27 probands and 27 unaffected siblings), for the family-based analysis, were included. RESULTS: The genome-wide QTL analysis identified four single nucleotide polymorphisms (SNPs) (rs7684645 near APELA, rs12538843 near YAE1D1 and POU6F2, rs11074258 near MCTP2, and rs34396552 near CIDEA) that were significantly associated with the number of inattention symptoms in ADHD. These SNPs showed possible association with ADHD in the family-based GWAS, and with hyperactivity-impulsivity in genome-wide QTL analyses. Moreover, association signals in the family-based QTL analysis for the number of inattention symptoms were clustered near genes IL10, IL19, SCL5A9, and SKINTL. CONCLUSION: We have identified four QTLs with genome-wide significance and several promising candidates that could potentially be associated with ADHD (CXCR4, UPF1, SETD5, NALCN-AS1, ERC1, SOX2-OT, FGFR2, ANO4, and TBL1XR1). Further replication studies with larger sample sizes are needed.

The Association of COMT Gene Polymorphism and Tourette Syndrome: A Family Based and Case Control Study

OBJECTIVES: Tourette disorder is known to be a disease with a strong genetic trait. There has been some recent research on the relationship between the allelic frequency distribution and Tourette disorder. In Korea, the relationship between the genetic type and the alleles for the COMT gene has been studied in Tourette patients. METHODS: Seventy two patients who were diagnosed with Tourette disorder according to the DSM-IV diagnostic criteria were selected for this study. The diagnosis and clinical features were confirmed by the Yale Global Tic Severity Scale. For the control group, the parents of the patients were chosen. Blood samples were taken from the 289 subjects. DNA was extracted from the blood lymphocytes and PCR was performed for assessing COMT gene. RESULTS: On comparing the Tourette disorder transmitted group and the not-transmitted group, no significant difference was seen between the COMT genetic type and the allelic distribution. CONCLUSION: Even though this result is viewed that there is no relationship between Tourette disorder and the COMT gene, it is difficult to firmly accept this negative result. Follow up studies with a larger patient population or pure subgroups are expected in the future.

Association of DRD4 Gene Polymorphism on Attention Deficit Hyperactivity Disorder: Preliminary Study / 대한정신약물학회지

OBJECTIVE: Attention deficit hyperactivity disorder (ADHD) has a strong genetic basis, and the relationship between the allele frequency distribution and ADHD has been researched actively. We investigated the association between the DRD4 genotype and ADHD patients in Korea, in comparison with case control and family based control groups. METHODS: The study enrolled 118 patients diagnosed with ADHD according to the DSM-IV diagnostic criteria and their parents (n = 70), and 84 normal children were recruited as controls. The clinical features of the patients were confirmed using the Korean versions of the Child Behavior Checklist (CBCL), Conners' parent rating scale, Attention Deficit Diagnostic System, and Spielberger state/trait anxiety scale. Blood samples were taken from the 272 subjects. DNA was extracted from blood lymphocytes. PCR was performed to examine DRD4 polymorphisms. Allele and genotype frequencies were compared using the Chi-square test for the casecontrol analysis and the transmission disequilibrium test (TDT) for the family-based analyses. RESULTS: In comparing the ADHD transmitted group with the not transmitted group, no significant differences were seen in the DRD4 genotype, allele distribution, or ADHD. CONCLUSION: However, there was a trend to an association between the DRD4 genotype, allele distribution, and ADHD for the case-control analysis. Follow-up studies with more patients or pure subgroups are needed.