MSGID: 1:317/3 641bd5f4   
   PID: hpt/lnx 1.9.0-cur 2019-01-08   
   TID: hpt/lnx 1.9.0-cur 2019-01-08   
    New NIH study reveals shared genetic markers underlying substance use   
   disorders    
    Breakthrough findings could lead to more effective prevention and   
   treatment strategies for multiple substance use disorders    
      
     Date:   
         March 22, 2023   
     Source:   
         NIH/National Institute on Drug Abuse   
     Summary:   
         By combing through genomic data of over 1 million people of   
         European or African descent, scientists have identified genes   
         commonly inherited across addiction disorders, regardless of   
         the substance being used. This dataset -- one of largest and most   
         diverse of its kind -- may help reveal new treatment targets across   
         multiple substance use disorders, including for people diagnosed   
         with more than one. The findings also reinforce the role of the   
         dopamine system in addiction, by showing that the combination   
         of genes underlying addiction disorders was also associated with   
         regulation of dopamine signaling.   
      
      
         Facebook Twitter Pinterest LinkedIN Email   
   FULL STORY   
   ==========================================================================   
   By combing through genomic data of over 1 million people, scientists have   
   identified genes commonly inherited across addiction disorders, regardless   
   of the substance being used. This dataset -- one of the largest of its   
   kind -- may help reveal new treatment targets across multiple substance   
   use disorders, including for people diagnosed with more than one. The   
   findings also reinforce the role of the dopamine system in addiction,   
   by showing that the combination of genes underlying addiction disorders   
   was also associated with regulation of dopamine signaling.   
      
      
   ==========================================================================   
   Published today in Nature Mental Health, the study was led by researchers   
   at the Washington University in St. Louis, along with more than 150   
   coauthors from around the world. It was supported by the National   
   Institute on Drug Abuse (NIDA), the National Institute on Alcohol Abuse   
   and Alcoholism (NIAAA), the National Institute of Mental Health (NIMH),   
   the Eunice Kennedy Shriver National Institute of Child Health and Human   
   Development, and the National Institute on Aging.   
      
   There has been limited knowledge of the molecular genetic underpinnings of   
   addiction until now. Further, most clinical trials and behavioral studies   
   have focused on individual substances, rather than addiction more broadly.   
      
   Genetics play a key role in determining health throughout our lives,   
   but they are not destiny. Our hope with genomic studies is to further   
   illuminate factors that may protect or predispose a person to substance   
   use disorders -- knowledge that can be used to expand preventative   
   services and empower individuals to make informed decisions about drug   
   use," said NIDA Director, Nora Volkow, M.D.   
      
   "A better understanding of genetics also brings us one step closer to   
   developing personalized interventions that are tailored to an individual's   
   unique biology, environment, and lived experience in order to provide   
   the most benefits."  In 2021, more than 46 million people in the United   
   States aged 12 or older had at least one substance use disorder, and   
   only 6.3% had received treatment.   
      
   Moreover, people who use drugs are facing an increasingly dangerous   
   drug supply, now often tainted with fentanyl. Approximately 107,000   
   people died of drug overdoses in 2021, and 37% of these deaths involved   
   simultaneous exposure to both opioids and stimulant drugs. Drug use and   
   addiction represent a public health crisis, characterized by high social,   
   emotional, and financial costs to families, communities, and society.   
      
   Substance use disorders are heritable and influenced by complex   
   interactions among multiple genes and environmental factors. In recent   
   decades, a data-rich method, called genome-wide association, has emerged   
   to try to identify specific genes involved in certain disorders. This   
   method involves searching entire genomes for regions of genetic variation,   
   called single-nucleotide polymorphisms (SNPs), that associate with the   
   same disease, disorder, condition, or behavior among multiple people.   
      
   In this study, researchers used this method to pinpoint areas in the   
   genome associated with general addiction risk, as well as the risk of   
   specific substance use disorders -- namely, alcohol, nicotine, cannabis,   
   and opioid use disorders -- in a sample of 1,025,550 individuals with   
   genes indicating European ancestry and 92,630 individuals with genes   
   indicating African ancestry.   
      
   "Using genomics, we can create a data-driven pipeline to prioritize   
   existing medications for further study and improve chances of discovering   
   new treatments. To do this accurately, it's critical that the genetic   
   evidence we gather includes globally representative populations and   
   that we have members of communities historically underrepresented in   
   biomedical research leading and contributing to these kinds of studies,"   
   said Alexander Hatoum, Ph.D., a research assistant professor at Washington   
   University in St. Louis and lead author of the study.   
      
   Hatoum and the research team discovered various molecular patterns   
   underlying addiction, including 19 independent SNPs significantly   
   associated with general addiction risk and 47 SNPs for specific substance   
   disorders among the European ancestry sample. The strongest gene signals   
   consistent across the various disorders mapped to areas in the genome   
   known to control regulation of dopamine signaling, suggesting that   
   genetic variation in dopamine signaling regulation, rather than in   
   dopamine signaling itself, is central to addiction risk.   
      
   Compared to other genetic predictors, the genomic pattern identified here   
   was also a more sensitive predictor of having two or more substance   
   use disorders at once. The genomic pattern also predicted higher   
   risk of mental and physical illness, including psychiatric disorders,   
   suicidal behavior, respiratory disease, heart disease, and chronic pain   
   conditions. In children aged 9 or 10 years without any experience of   
   substance use, these genes correlated with parental substance use and   
   externalizing behavior.   
      
   "Substance use disorders and mental disorders often co-occur, and we   
   know that the most effective treatments help people address both issues   
   at the same time.   
      
   The shared genetic mechanisms between substance use and mental disorders   
   revealed in this study underscore the importance of thinking about these   
   disorders in tandem," said NIMH Director Joshua A. Gordon, M.D., Ph.D.   
      
   Genomic analysis in the African ancestry sample revealed one SNP   
   associated with general addiction risk and one substance-specific SNP for   
   risk of alcohol use disorder. The dearth of findings here underscores   
   ongoing disparities in data inclusion of globally representative   
   populations that must be addressed to ensure data robustness and accuracy,   
   Hatoum and co-authors note.   
      
   The inclusion of data from different ancestral groups in this study cannot   
   and should not be used to assign or categorize variable genetic risk for   
   substance use disorder to specific populations. As genetic information   
   is used to better understand human health and health inequities,   
   expansive and inclusive data collection is essential. NIDA and other   
   Institutes at NIH supported a recently released report on responsible   
   use and interpretation of population-level genomic data by the National   
   Academies of Sciences, Engineering, and Medicine.   
      
   While Hatoum and colleagues have identified a genetic pattern indicating   
   broad addiction risk, they note that substance use-specific diagnoses   
   still have meaning. "The current study validates previous findings of   
   alcohol-specific risk variants, and, importantly, makes this finding in   
   a very large and more diverse study population," said NIAAA Director   
   George F. Koob, Ph.D. "The finding of shared genetic risk variants   
   across different substance use disorders provides insight into some of   
   the mechanisms that underlie these disorders and the relationships with   
   other mental health conditions. Together the findings of alcohol-specific   
   risk variants and common addiction-related variants provide powerful   
   support for individualized prevention and treatment."  This study was   
   supported by multiple grants: NIDA (T32DA007261, DA054869, R01DA054750,   
   K02DA032573, U01DA055367, K01DA051759, DP1DA054394, R33DA047527); NIAAA   
   (K01AA030083, R21AA027827, R01AA027522, F31AA029934, T32AA028259); NIMH   
   (K23MH121792, T32MH014276, R01MH120219); NIA (RF1AG073593, P30AG066614);   
   NICHD (P2CHD042849)   
       * RELATED_TOPICS   
             o Health_&_Medicine   
                   # Personalized_Medicine # Controlled_Substances #   
                   Diseases_and_Conditions # Mental_Health_Research   
             o Mind_&_Brain   
                   # Addiction # Illegal_Drugs # Disorders_and_Syndromes #   
                   Mental_Health   
       * RELATED_TERMS   
             o Addiction o Drug_addiction o Alcoholism o Dopamine o   
             Sleep_disorder o Mental_illness o Personality_disorder o   
             Dopamine_hypothesis_of_schizophrenia   
      
   ==========================================================================   
   Story Source: Materials provided by   
   NIH/National_Institute_on_Drug_Abuse. Note: Content may be edited for   
   style and length.   
      
      
   ==========================================================================   
   Journal Reference:   
      1. Alexander S. Hatoum, Sarah M. C. Colbert, Emma C. Johnson,   
      Spencer B.   
      
         Huggett, Joseph D. Deak, Gita A. Pathak, Mariela V. Jennings,   
         Sarah E.   
      
         Paul, Nicole R. Karcher, Isabella Hansen, David A. A. Baranger,   
         Alexis Edwards, Andrew D. Grotzinger, Daniel E. Adkins, Amy   
         E. Adkins, Mervi Alanne-Kinnunen, Jeffry C. Alexander, Fazil Aliev,   
         Silviu-Alin Bacanu, Anthony Batzler, Joanna M. Biernacka, Laura   
         J. Bierut, Tim B. Bigdeli, Anna Blagonravova, Jason D. Boardman,   
         Joseph M. Boden, Dorret I. Boomsma, Sandra A. Brown, Kathleen   
         K. Bucholz, Danfeng Chen, Li-Shiun Chen, Doo- Sup Choi, S. Patricia   
         Chou, Sven Cichon, William E. Copeland, Robin P.   
      
         Corley, Franziska Degenhardt, Marta Di Forti, Nancy Diazgranados,   
         Danielle M. Dick, Benjamin W. Domingue, Johan G. Eriksson,   
         Lindsay A.   
      
         Farrer, Jerome C. Foo, Tatiana M. Foroud, Louis Fox, Josef Frank,   
         Mark A.   
      
         Frye, Wolfgang Gaebel, Raul R. Gainetdinov, Ina Giegling, Nathan A.   
      
         Gillespie, Alison M. Goate, David Goldman, Scott Gordon, Laura   
         M. Hack, Dana B. Hancock, Kathleen Mullan Harris, Annette   
         M. Hartmann, Andrew C.   
      
         Heath, Stefanie Heilmann-Heimbach, Stefan Herms, Victor Hesselbrock,   
         John K. Hewitt, Ian Hickie, Colin Hodgkinson, Per Hoffmann,   
         Christian Hopfer, John Horwood, Jouke Jan Hottenga, Daniel Patrick   
         Howrigan, William G.   
      
         Iacono, Marcus Ising, Eric O. Johnson, Jaakko Kaprio, Victor   
         M. Karpyak, Kenneth S. Kendler, Martin A. Kennedy, Margaret Keyes,   
         Alexander Kibitov, Falk Kiefer, Bettina Konte, John Kramer,   
         Kenneth Krauter, Evgeny M.   
      
         Krupitsky, Samuel Kuperman, Jari Lahti, Marius Lahti-Pulkkinen,   
         Dongbing Lai, Anastasia Levchenko, Lannie Ligthart, Penelope   
         A. Lind, Susanne Lucae, Michael T. Lynskey, Pamela A. F. Madden,   
         Hermine H. Maes, Patrik K. E. Magnusson, Brion S. Maher, Karl Mann,   
         Satu Ma"nnisto", Nicholas G.   
      
         Martin, Hamdi Mbarek, Matt McGue, Matthew B. McQueen, Sarah   
         E. Medland, Jacquelyn L. Meyers, Grant W. Montgomery, Bertram   
         Mu"ller-Myhsok, Benjamin M. Neale, Elliot C. Nelson, Markus   
         M. No"then, John I.   
      
         Nurnberger, Aarno Palotie, Teemu Palviainen, John F. Pearson,   
         Nancy L.   
      
         Pedersen, Brenda W. J. H. Penninx, Roseann E. Peterson, Bernice   
         Porjesz, Ulrich W. Preuss, Diego Quattrone, Katri Ra"ikko"nen,   
         Maureen D.   
      
         Reynolds, John P. Rice, Monika Ridinger, Marcella Rietschel,   
         Brien P.   
      
         Riley, Samuli Ripatti, Richard J. Rose, Dan Rujescu, Ksenia   
         V. Rybakova, Euijung Ryu, Nancy L. Saccone, Jessica E. Salvatore,   
         Norbert Scherbaum, Marc A. Schuckit, Melanie Schwandt, Pei-Hong   
         Shen, Richard Sherva, Judy Silberg, Michael C. Stallings,   
         Dan J. Stein, Fabian Streit, Jana Strohmaier, Ralph E. Tarter,   
         Nathaniel Thomas, Michael M. Vanyukov, Scott Vrieze, Tamara L. Wall,   
         Raymond K. Walters, Bradley T. Webb, Robbee Wedow, Frank Wendt,   
         Leah Wetherill, John B. Whitfield, Stephanie Witt, Norbert Wodarz,   
         Margaret J. Wright, Sarah M. Hartz, Stephanie Zellers, Haitao Zhang,   
         Hongyu Zhao, Hang Zhou, Peter Zill, Lea Zillich, Elliot M.   
      
         Tucker-Drob, Henry R. Kranzler, Lea K. Davis, Sandra Sanchez-Roige,   
         Renato Polimanti, Joel Gelernter, Howard J. Edenberg, Ryan Bogdan,   
         Arpana Agrawal. Multivariate genome-wide association meta-analysis   
         of over 1 million subjects identifies loci underlying multiple   
         substance use disorders. Nature Mental Health, 2023; 1 (3): 210 DOI:   
         10.1038/s44220- 023-00034-y   
   ==========================================================================   
      
   Link to news story:   
   https://www.sciencedaily.com/releases/2023/03/230322140341.htm   
      
   --- up 1 year, 3 weeks, 2 days, 10 hours, 50 minutes   
    * Origin: -=> Castle Rock BBS <=- Now Husky HPT Powered! (1:317/3)   
   SEEN-BY: 15/0 106/201 114/705 123/120 153/7715 226/30 227/114 229/110   
   SEEN-BY: 229/111 112 113 307 317 400 426 428 470 664 700 292/854 298/25   
   SEEN-BY: 305/3 317/3 320/219 396/45   
   PATH: 317/3 229/426