Heping Zhang

..We examined whether retinal secretions that increase the barrier functions of tight junctions in vitro also make gene expression in general more in vivo-like...

..We correctly identify the association between gene FLT1 and phenotype Affect, although there exist other false positives in our results. Our analyses are performed without knowledge of the underlying simulating model...

..Our method identified 38 markers (in 65 genes) that are significantly associated with the phenotype Affected and correctly identified two causal genes, SIRT1 and PDGFD...

..In addition to numerical improvement, the main advantage of deterministic forests is reproducibility and scientific interpretability of all steps in tree construction...

..The degree of saving in the required sample sizes varies among different models and allele frequencies. The reduction is most dramatic (a 28-fold reduction) for a rare recessive gene...

..The analysis of a real example is also presented to illustrate the application and interpretation of MASAL. Open questions are posed for further investigation...

..This review is purposely meant to be relatively short and of practical use for the space constraints of typical federal grant proposals...

..Although the heritability of nicotine dependence (ND) is well documented and many candidate genetic regions have been identified, few of them were confirmed. This may be, in part, due to analytic methods that sacrifice power...

..We further demonstrated the advantage of our test by revealing a significant association (P = 0.00067) between alcohol dependence and a SNP in the growth-associated protein 43...

..Our multivariate linkage analysis found linkage evidence on two regions on chromosome 4: around marker GABRB1 at 51.4 cM and marker FABP2 at 116.8 cM (unadjusted p-value = 0.00006)...

..g. genetic markers), there is still much utility in exploring whether it is possible to estimate treatment efficacy based on demographic and baseline variables...

..However, they cannot deal with the data generated by recent genotyping platforms for single nucleotide polymorphisms due to the massive size of the data and its excessive memory demand...

..In addition, competing classification trees are displayed, which suggest that different genes may coregulate colon cancers...

..Moreover, females manifest alcoholism at a lower threshold, and there is no sex-specific familial transmission of alcoholism after adjustment for the threshold effect...

..In addition to the fitting of growth curves, we demonstrate particularly how to explore and estimate the underlying covariance structures for the longitudinal data that were collected from a rather irregular schedule...

..Our purpose is to demonstrate the great potential of tree-based analyses for genetic studies, and discuss some issues that warrant further investigation...

..So far, little attention has been paid to examine the relationship among key factors in genetic longitudinal studies including power, the number of families or sibships, and the number of repeated measures per individual subjects...

..We estimate parameters from both the tolerance distribution and the risk function for a large group of mice exposed to very low levels of a known carcinogen...

..Sulfate level was not related to the incidence of new episodes but was associated with the duration of the episodes...

..000003. Although P values were not adjusted for multiple comparison, nearly all were much smaller than the customary significance level of.0001 for genomewide scans...

..1) and has been shown by others to have altered expression levels in breast cancer. Nonetheless, our identified genes warrant further investigation as to whether they play a role in the etiology of breast cancer...

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..We concluded that the SH3BP5-NR2C2 region on Chromosome 3 might harbor causal loci for alcohol and nicotine co-dependence...

..The other three SNPs (rs485874, rs718251, and rs1869907) are identified for the first time using this data set, underscoring the potential power of our proposed test...

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..We then examined the power of GABHS infections and measures of psychosocial stress to predict future tic, obsessive-compulsive (OC), and depressive symptom severity...

..To assess the genetic contribution to late-onset sepsis in twins in the newborn intensive care unit...

..We found 49.7% (p = 0.04) of the variance in liability to RDS was the result of genetic factors alone. We conclude that there is a significant genetic susceptibility to RDS in preterm infants...

..The long-term effectiveness of this AIDS-bereavement intervention for psychiatrically distressed people with HIV/AIDS supports the need for tailored interventions among those at risk for complicated grief responses...

..Our finding underscores the importance of accommodating and controlling for covariate effects in discovering genetic variants associated with complex disorders...

..The likelihood-ratio test is used for testing evidence of linkage. AVAILABILITY: The LOT program is available for download at http://c2s2.yale.edu/software/LOT/..

..CONCLUSION: Obsessive-compulsive disorder symptoms in children with TS became more severe at a later age and were more likely to persist than tic symptoms...

..We conclude that the PHF3-PTP4A1 region appears to harbor a causal locus for alcohol dependence, and proteins encoded by PHF3 and/or PTP4A1 might play a functional role in the disorder...

..A genomic approach was used to investigate the extent of this remodeling...

..Interestingly, one of our most promising linkage regions, includes a region previously identified as linked to PD...

..This study was carried out to investigate whether cytokines associated with the innate immune response or T cell activation were altered under baseline conditions and during periods of symptom exacerbation...

..We also compare the methods with mean identity-by-descent tests and transmission/disequilibrium tests that do not use age of onset information...

..Our analysis also identified genes that were reported in other studies of alcoholism and identified new genes or single-nucleotide polymorphisms that can be useful candidates for future studies...

..This study was designed to evaluate the psychometric properties of the YCGSI...

..Thus, hypoxia-induced reduction in myelin-derived axon outgrowth inhibitors appears to contribute axonal misconnection to the pathology of very low birth weight infants...

..We conclude that familial factors contribute significantly to OC symptom dimension phenotypes in GTS families. This familial contribution could be genetic or environmental...

..Thus, the importance of this work is twofold: it proposes a powerful and flexible method to identify high-risk haplotypes and their interactions and reveals a potentially protective variant for AMD...

..In the present study, we comprehensively examined the associations between rare ADH variants [minor allele frequency (MAF) <0.05] and alcohol dependence, with several other neuropsychiatric and neurological disorders as reference...

..To identify risk factors for pregnancy outcomes in couples treated with intracervical or intrauterine insemination, with or without superovulation for unexplained or male-factor infertility...

..Our findings underscore the importance of considering multiple addiction types and the importance of considering population and gender stratification when analyzing data with heterogeneous population...

..These data demonstrate, for the first time, the significant genetic susceptibility for bronchopulmonary dysplasia in preterm infants...

..We suggest that cortical neurogenesis may play a significant role in repairing neuronal losses after neonatal injury...

..g., children nested within families). Findings are consistent with an attachment perspective on parenting suggesting that the internal psychological processes of a parent play a critical role in the continuity of parenting...

..1% of the variance in liability for retinopathy of prematurity. CONCLUSION: In addition to prematurity and environmental factors, there is a strong genetic predisposition to retinopathy of prematurity...

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..We conclude that our memory management approach is simple, efficient, and effective for genome-wide association studies...

..Further analysis of this region indicates a strong association to the rheumatoid arthritis status...

..When disruptive behavior problems are present, there is an additional burden on children's social and family functioning...

..In addition to prematurity and environmental factors, we hypothesized that genetic factors play a significant role in this condition...

..Random forests represent a very useful approach for this purpose, using a variable importance score. This importance score has several shortcomings. We propose an alternative importance measure to overcome those shortcomings...

..Our findings reveal the potential of multivariate adaptive splines in deciphering complex and important transcriptional regulatory networks in eukaryotes...

..Our findings suggest that bioinformatic tools are useful in predicting SNP functionality and may facilitate future genetic epidemiological studies...

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..Cumulative logit models were used in our analysis. The choice of treatment modality is sex specific, although sex did not appear to be a significant factor for treatment effectiveness when we controlled for other explanatory variables...

..Further investigations will be needed to fully determine the role of cortical-subcortical networks in ictal neocortical dysfunction and may reveal treatments to prevent this important negative consequence of temporal lobe epilepsy...

..In terms of gene findings, our results validate many genes that were either reported from the analysis of the same dataset or based on animal studies for substance dependence...

..We conducted a permutation test to assess the associations between MASAL selected markers and triglycerides trait and report significant gene-gene and gene-environment interaction effects on the trait of interest...

..However, our method identified three markers at 4q34-35 (P = 0.0009), 5q35.2-35.3 (P = 0.0001), and 17q25 (P = 0.0005) that manifest significant allele sharing...

..Results suggest that prenatally cocaine-exposed children show delayed developmental indices, particularly in their mental performance, but their trajectories across time are similar to those from impoverished, non-cocaine-exposed groups...

..This method has been successfully applied to protein data, provided by the Department of Radiology and Chemistry at Duke University...

..As one of the first investigation to model more than two time points of structural MRI data over time, our findings add insight into how AD and aMCI males and females differ from controls and from each other over time...

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..These patterns reveal a global dysynchrony in the maturation programs of the hypoxic developing brain, and offer insights into the vulnerabilities of processes that guide early postnatal cerebral maturation...

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..Application of the spectrum concept provides coverage of treated but undiagnosed cases of social phobia as well as those who vacillate across the diagnostic threshold over time...

..In addition, Ph.D. candidates in biostatistics who will work with our biostatistics faculty on developing new techniques for the analysis of longitudinal data on older persons will also be eligible for support. ..

..Dr. Stan Kasl has been the Principal Investigator since 1975; however, Dr. Heping Zhang has taken over as Program Director and Dr. Kasl has become Co-Director since 2002...

..We are committed to the role and responsibilities of the DCC as stated in the RFA and have full institutional support in this endeavor. ..

..That in turn leads to better prevention and treatment strategies. ..

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..This award enables the PI to invest a major effort in a relatively long term to develop some of the critically needed, timely statistical methods and software, which help us advance our understanding of substance use disorders. ..

..They further state that identifying these pathways will ultimately assist in the development of an empirical basis for the primary prevention of secondary alcoholism. ..

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..Although the focus of application is on genetic epidemiology of SUBs, our methodologies will be useful for understanding complex ordinal traits in general. ..

..That in turn leads to better prevention and treatment strategies. ..