This application """"""""A developmental model of gene-environment interplay in SUDs"""""""" (substance use disorders), responds to NIDA RFA-DA-70-012. It brings together investigators with existing data that meet the requirements of the U01: Duke University (sample N-1400) and Virginia Commonwealth University (N-1000). UNC Chapel Hill, as well as Duke and VCU, will contribute expertise psychiatric genetics, bioinformatics and statistics, as well as in the clinical care of substance abusing and psychiatric patients. All the investigators have worked together for many years on other projects and grants. The studies have large, representative population-based samples;multiple waves of data collection on males and females across childhood to adulthood;DSM-IV diagnoses and scales on SUD at every stage from initiation to addiction;details of age at initiation, type, amount, context, and associated impairment;and a wide range of related phenotypes and environmental risk factors at different levels of analysis, from biological to social. One study has blood samples;one has buccal cells and will collect blood. Both have or are collecting participant consent to deposit information in the NIDA repository and share data with other qualified researchers outside their own group. The model underlying this application has three components: (1) the existence and relevance of two phenotypes: (i) initiation of the use of a substance and (ii) progression to SUD, each with both common and specific genetic and environmental risk factors;(2) the presence of genetic and environmental risk and protective factors that are common across drugs;(3) the differential influence of aspects of development on the likelihood of drug initiation and progression in the presence/absence of genetic and environmental risk.
Specific Aims : (1) Finalize blood collection and DNA extraction;(2) Integrate variables across data sets;(3) Conduct genome wide association (GWA) genotyping for all subjects;(4) Conduct statistical analysis of genotype and haplotype associations for the initiation and progression for candidate gene SNP lists (5) Finalize list of GWA SNPs that are highly plausible candidate genes for initiation and progression, with and without environmental/developmental interplay;(6) Examine gene-environment-development interplay;(7) Throughout, communicate with other U01 members;(8) prepare data for inclusion in NIDA repository;(9) Help develop guidelines for including non-clinical samples in the repository.
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