Substance Use Disorders
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The SUD workgroup has been a part of the PGC since 2014. We focus on the study of use and misuse of alcohol, cannabis, cocaine, opioids, tobacco and other illicit substances. Substance use disorders cause a tremendous amount of suffering to those with the disorder and to their families, and have significant societal costs. Genetic variations are amongst the major factors that contribute to the differences among individuals in risk for these disorders. Our goals are to identify the genetic contributions to substance use disorders (alcohol, cannabis, opioids, cocaine, nicotine and other illicit substances) and the biological pathways that underlie their development. There are differences between the genetic underpinnings of substance use (e.g., typical alcohol consumption, ever using cannabis) and substance use disorders/addiction that we also wish to identify. Substance use disorders are comorbid with many other psychiatric and somatic disorders, and relate to psycho-social outcomes, and one of our goals is to understand the genetics that contributes to these associations. As part of our work to understand the genetic contributions to these disorders, we collaborate with neuroscientists, cross-species translational researchers and biostatisticians.
Our primary approach is by encouraging groups who have genetic data on these disorders to join our group as active participants, so that we can aggregate the data and analyse it. The contributions of individual genetic variants are very small, so identifying them requires very large numbers of individuals for analysis. All investigators who contribute data retain control of their data, benefit from the rigorous quality control that we perform on all incoming datasets, contribute scientifically to resulting publications, and consult on the overall research direction of the team.
We welcome your participation and are eager to collaborate with investigators who might be willing to share raw genotypic data or effect sizes. We do not have resources to fund genome-wide genotyping or sequencing, but are happy to provide letters of support for groups who are requesting genotyping of their data. We receive funding support from the National Institute on Drug Abuse (NIDA) to aggregate and analyze genomewide association studies.
Walters et al. 2018. Transancestral GWAS of alcohol dependence reveals common genetic underpinnings with psychiatric disorders. Nature Neuroscience 21(12):1656–1669. PMID: 30482948 https://rdcu.be/bb0e6
Polimanti R, Peterson RE, Ong JS, MacGregor S, Edwards AC, Clarke TK, Frank J, Gerring Z, Gillespie NA, Lind PA, Maes HH, Martin NG, Mbarek H, Medland SE, Streit F; Major Depressive Disorder Working Group of the Psychiatric Genomics Consortium, Agrawal A, Edenberg HJ, Kendler KS, Lewis CM, Sullivan PF, Wray NR, Gelernter J, Derks EM. (2019) Evidence of causal effect of major depression on alcohol dependence: findings from the psychiatric genomics consortium. Psychol Med. 49(7):1218-122. PMID: 30929657. PMCID: PMC6565601 DOI: 10.1017/S0033291719000667
Polimanti R, Walters RK, Johnson EC, McClintick JN, Adkins AE, Adkins DE, Bacanu S-A, Bierut LJ, Bigdeli TB, Brown S, Bucholz KK, Copeland WE, Costello EJ, Degenhardt L, Farrer LA, Foroud TM, Fox L, Goate AM, Grucza R, Hack LM, Hancock DB, Hartz SM, Heath AC, Hewitt JK, Hopfer CJ, Johnson EO, Kendler KS, Kranzler HR, Krauter K, Lai D, Madden PAF, Martin NG, Maes HH, Nelson EC, Peterson RE, Porjesz B, Riley BP, Saccone N, Stallings M, Wall TL, Webb BT, Wetherill L, Psychiatric Genomics Consortium Substance Use Disorders Workgroup, Edenberg HJ, Agrawal A, Gelernter J, (2020) Leveraging genome-wide data to investigate differences between opioid use vs. opioid dependence in 41,176 individuals from the Psychiatric Genomics Consortium. Molecular Psychiatry. 26 Feb 2020 [Epub ahead of print] PMID: 32099098. DOI: 10.1038/s41380-020-0677-9