Our goal is to develop new analytic tools that can be used to identify genetic variation more efficiently and accurately than the existing methods and then test them in the datasets of psychiatric disorders or other complex human diseases. We have been actively working with both intramural and extramural collaborators. A few examples include 1) Using pathway-bases approaches to detect genetic domains underlying the pharmacotherapy options of serotonin reuptake inhibitors effect in study subjects affected with obsessive compulsive disorder (OCD); 2) Establishing efficient pipelines for exome sequencing analyses in a Latino population (schizophrenia and bipolar); and 3) Developing an efficient test for nonlinear dependence of two continuous variables. This presents a new way of testing nonlinear dependence between two continuous variables. There is a need to improve the current version of the software so that it can be used by individuals who use Linux-based computer or desktops to run their analysis. Summary We collaborated with extramural scientists and developed a new statistical method called CANOVA. Using this method, one can generalize the within category variance in traditional analysis of variance (ANOVA). Using extensive simulations, we extensively evaluated the performance of CANOVA. We then applied CANOVA to a real dataset and showed that the power of CANOVA performs better when the correlation is highly non-linear. In addition, we developed a novel mixture model to estimate the time to antidepressant effect onset and its association with covariates such as age, gender and baseline anxiety. We evaluated the model's overall utility and performance via extensive simulations. We demonstrated its use by application to a longitudinal dataset from the Sequenced treatment Alternatives to Relieve Depression (STAR*D) study. Our algorithm successfully identified age and anxiety status as significant factors in influencing the onset distribution of citalopram. And we developed a pathway-based pipeline which can be used to link genome-wide association study signals to several important biological pathways. We used our own pipelines to analyze drug response on Obsessive Compulsive Disorder (OCD) GWAS data to select significant pathways. In a recent publication, we reported the suggestive roles of genes in the glutamatergic neurotransmission system and the serotonergic system. The results presented may provide new insights into genetic mechanisms underlying treatment response in OCD. More recently, we applied the same approach to seeking genetic variants underlying antidepressants such as ketamine. The potential findings will be reported in the future.

Project Start
Project End
Budget Start
Budget End
Support Year
6
Fiscal Year
2016
Total Cost
Indirect Cost
Name
U.S. National Institute of Mental Health
Department
Type
DUNS #
City
State
Country
Zip Code
Qin, H; Samuels, J F; Wang, Y et al. (2016) Whole-genome association analysis of treatment response in obsessive-compulsive disorder. Mol Psychiatry 21:270-6
Xu, Yong; Yao Shugart, Yin; Wang, Guoqiang et al. (2016) Altered expression of mRNA profiles in blood of early-onset schizophrenia. Sci Rep 6:16767
Wang, Zhiqiang; Yang, Bixiu; Liu, Yansong et al. (2015) Further evidence supporting the association of NKAPL with schizophrenia. Neurosci Lett 605:49-52
Wang, Yi; Li, Yi; Cao, Hongbao et al. (2015) Efficient test for nonlinear dependence of two continuous variables. BMC Bioinformatics 16:260
Mattheisen, M; Samuels, J F; Wang, Y et al. (2015) Genome-wide association study in obsessive-compulsive disorder: results from the OCGAS. Mol Psychiatry 20:337-44
Wang, Jicai; Cao, Hongbao; Liao, Yanhui et al. (2015) Three dysconnectivity patterns in treatment-resistant schizophrenia patients and their unaffected siblings. Neuroimage Clin 8:95-103
Zhang, Fuquan; Xu, Yong; Cao, Hongbao et al. (2015) Mapsnp: an R package to plot a genomic map for single nucleotide polymorphisms. PLoS One 10:e0123609
Zhang, Fuquan; Xu, Yong; Shugart, Yin Yao et al. (2015) Converging evidence implicates the abnormal microRNA system in schizophrenia. Schizophr Bull 41:728-35
Zhang, Fuquan; Shugart, Yin Yao; Yue, Weihua et al. (2015) Increased Variability of Genomic Transcription in Schizophrenia. Sci Rep 5:17995
Samuels, Jack; Shugart, Yin Yao; Wang, Ying et al. (2014) Clinical correlates and genetic linkage of social and communication difficulties in families with obsessive-compulsive disorder: Results from the OCD Collaborative Genetics Study. Am J Med Genet B Neuropsychiatr Genet 165B:326-36

Showing the most recent 10 out of 29 publications