Genetic and genomic research in addictions
Arpana AGRAWAL - Saint-Louis - USA
Substance Use Disorders (SUDs) are moderately heritable (40-60%). Genomewide association studies (GWAS) that interrogate variation across the genome are uncovering promising common loci associated with SUDs. The strength of this approach is that it minimizes high false discovery rates that are typically associated with candidate genotype research. GWAS findings have been particularly impressive for nicotine (e.g. rs16969968), which is now being investigated in treatment efficacy studies. For alcohol, recent studies have validated the role of rs1229984, a missense mutation in the alcohol dehydrogenase (ADH1B) gene but few other signals have been robustly replicated. For opioid dependence, SNPs in the gene encoding the mu-opioid receptor (OPRM1) as well as in other gene systems, such as CNIH3 and KCNG2, have also been noted. One study has provided insights into genomewide significant signals for cocaine dependence while two studies report findings for cannabis dependence. The goal of this presentation will be to provide an overview of these emerging findings in genomic studies of SUD, link them to heritability estimates to account for variation explained and to outline polygenic approaches to the study of the genetic architecture of SUD. The work of the recently formed Psychiatric Genomics Consortium’s Substance Use Disorders work group will be presented as a potential avenue for bringing together international investigators and datasets to accrue the largest possible samples for genomic analysis. Finally, implications of such large-scale genomic studies in delivering targets for treatment and prevention will be discussed.