Project description:Genome wide DNA methylation profiling of normal and methamphetamine (MA) abusers with different addiction susceptibility. The Illumina Infinium HumanMethylation450 Beadchip was used to obtain DNA methylation profiles in peripheral blood lymphocytes (PBLs). Samples included 8 health controls, 8 high MA addiction susceptibility (HMAS) abusers, and 8 high MA addiction susceptibility (LMAS) abusers.
Project description:<p> Genome wide analysis for addiction susceptibility genes is an affected sibling pair linkage study using subjects who were patients in methadone replacement treatment programs (MMTP). Such patients are highly addicted to opioids and usually to other addicting substances as well. For entry into the programs, patients had to be at least 18 years of age and had to satisfy DSM-IV criteria for opioid dependence. Despite their common substance use disorder diagnosis, patients enrolled in MMTPs generally have a heterogeneous mix of co-morbid psychiatric disorders including anti-social personality disorder, major depression and anxiety disorders, and often satisfy DSM-IV criteria of substance use disorders other than opioid dependence. Genetic analysis was carried out using genotyping data obtained from a 10K SNP array, and non-parametric linkage was assessed using MERLIN. This resulted in the identification of a linkage peak on 14q that overlapped the <a href="https://www.ncbi.nlm.nih.gov/gene/9369">NRXN3</a> gene (neurexin 3), which was previously identified as a potential candidate gene for addiction, and subsequently identified as a target gene in other addiction studies and autism. </p>
Project description:BackgroundClassical genetic studies provide strong evidence for heritable contributions to susceptibility to developing dependence on addictive substances. Candidate gene and genome-wide association studies (GWAS) have sought genes, chromosomal regions and allelic variants likely to contribute to susceptibility to drug addiction.ResultsHere, we performed a meta-analysis of addiction candidate gene association studies and GWAS to investigate possible functional mechanisms associated with addiction susceptibility. From meta-data retrieved from 212 publications on candidate gene association studies and 5 GWAS reports, we linked a total of 843 haplotypes to addiction susceptibility. We mapped the SNPs in these haplotypes to functional and regulatory elements in the genome and estimated the magnitude of the contributions of different molecular mechanisms to their effects on addiction susceptibility. In addition to SNPs in coding regions, these data suggest that haplotypes in gene regulatory regions may also contribute to addiction susceptibility. When we compared the lists of genes identified by association studies and those identified by molecular biological studies of drug-regulated genes, we observed significantly higher participation in the same gene interaction networks than expected by chance, despite little overlap between the two gene lists.ConclusionsThese results appear to offer new insights into the genetic factors underlying drug addiction.