Multivariate Genome-wide Association Meta-analysis Of Over 1 Million Subjects Identifies Loci Underlying Multiple Substance Use Disorders

This comprehensive study investigates the genetic factors contributing to substance use disorders (SUDs), including alcohol, tobacco, cannabis, and opioid use. It encompasses a vast dataset with over a million participants, representing diverse populations.   

Researchers took several steps to investigate the genetic factors associated with substance use disorders (SUDs). First, they categorized the effects of single-nucleotide polymorphisms (SNPs) into five sources of variation: a general addiction risk factor (referred to as addiction-rf), and risks specific to alcohol, nicotine, cannabis, and opioids. Second, they explored the biological pathways linked to the risk of these five SUD phenotypes using gene analysis and pathway enrichment techniques. Third, they examined existing medications that could potentially be repurposed for SUD treatment. Fourth, they evaluated the relationship between a polygenic risk score (PRS) derived from the addiction-rf and general SUD phenotypes in a separate case/control sample. Fifth, they investigated how genetic susceptibility to the addiction-rf might overlap with other traits, such as physical and mental health outcomes. Finally, they assessed whether the addiction-rf PRS was associated with medical diagnoses from electronic health records (EHRs) and behavioral traits in 9-10-year-old children who had limited exposure to substances. This study significantly advances our knowledge of the genetic foundations of addiction, encompassing both general and substance-specific factors, with potential implications for treatment and a broader understanding of how addiction risk relates to overall health. Click the link below to read more. 

 

Hatoum AS, Colbert SMC, Johnson EC, Huggett SB, Deak JD, Pathak GA, Jennings MV, Paul SE, Karcher NR, Hansen I, Baranger DAA, Edwards A, Grotzinger AD, Adkins DE, Adkins AE, Alanne-Kinnunen M, Alexander JC, Aliev F, Bacanu S-A, Batzler A, Biernacka JM, Bierut LJ, Bigdeli TB, Blagonravova A, Boardman JD, Boden JM, Boomsma DI, Brown SA, Bucholz KK, Chen D, Chen L-S, Choi D-S, Chou SP, Cichon S, Copeland WE, Corley RP, Degenhardt F, Di Forti M, Diazgranados N, Dick DM, Domingue BW, Eriksson JG, Farrer LA, Foo JC, Foroud TM, Fox L, Frank J, Frye MA, Gaebel W, Gainetdinov RR, Giegling I, Gillespie NA, Goate AM, Goldman D, Gordon S, Hack LM, Hancock DB, Harris KM, Hartmann AM, Heath AC, Heilmann-Heimbach S, Herms S, Hesselbrock V, Hewitt JK, Hickie I, Hodgkinson C, Hoffmann P, Hopfer C, Horwood J, Hottenga JJ, Howrigan DP, Iacono WG, Ising M, Johnson EO, Kaprio J, Karpyak VM, Kendler KS, Kennedy MA, Keyes M, Kibitov A, Kiefer F, Konte B, Kramer J, Krauter K, Krupitsky EM, Kuperman S, Lahti J, Lahti-Pulkkinen M, Lai D, Levchenko A, Ligthart L, Lind PA, Lucae S, Lynskey MT, Madden PAF, Maes HH, Magnusson PKE, Maher BS, Mann K, Männistö S, Martin NG, Mbarek H, McGue M, McQueen MB, Medland SE, Meyers JL, Montgomery GW, Müller-Myhsok B, Neale BM, Nelson EC, Nöthen MM, Nurnberger JI, Palotie A, Palviainen T, Pearson JF, Pedersen NL, Penninx BWJH, Peterson RE, Porjesz B, Preuss UW, Quattrone D, Räikkönen K, Reynolds MD, Rice JP, Ridinger M, Rietschel M, Riley BP, Ripatti S, Rose RJ, Rujescu D, Rybakova KV, Ryu E, Saccone NL, Salvatore JE, Scherbaum N, Schuckit MA, Schwandt M, Shen P-H, Sherva R, Silberg J, Stallings MC, Stein DJ, Streit F, Strohmaier J, Tarter RE, Thomas N, Vanyukov MM, Vrieze S, Wall TL, Walters RK, Webb BT, Wedow R, Wendt F, Wetherill L, Whitfield JB, Witt S, Wodarz N, Wright MJ, Hartz SM, Zellers S, Zhang H, Zhao H, Zhou H, Zill P, Zillich L, Tucker-Drob EM, Kranzler HR, Davis LK, Sanchez-Roige S, Polimanti R, Gelernter J, Edenberg HJ, Bogdan R, Agrawal A (2023) Multivariate genome-wide association meta-analysis of over 1 million subjects identifies loci underlying multiple substance use disorders. Nature Mental Health, 1(3), 210-223. DOI: 10.1038/s44220-023-00034-y.