MSGID: 1:317/3 63e5c866   
   PID: hpt/lnx 1.9.0-cur 2019-01-08   
   TID: hpt/lnx 1.9.0-cur 2019-01-08   
    Researchers link 27 genetic variants to ADHD    
      
     Date:   
         February 9, 2023   
     Source:   
         Aarhus University   
     Summary:   
         A large international study has identified 27 loci in the human   
         genome with genetic variants that increase the risk of ADHD. This   
         is more than twice as many as previous studies have found.   
      
      
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   FULL STORY   
   ==========================================================================   
   Why do some people get ADHD, while others do not? And how early in life   
   or in the womb is the seed of ADHD sown?   
      
   ==========================================================================   
   Researchers from Aarhus University have come closer to answering this   
   question in a large study, which has just been published in the journal   
   Nature Genetics.   
      
   Together with national and international partners, the researchers have   
   studied more than six million genetic variants in 38,691 people with   
   ADHD and 186,843 people without ADHD. By this means it has been possible   
   to identify 27 genetic risk variants for the common neurodevelopmental   
   disorder.   
      
   Risk genes are expressed in the brain and neurons The study is   
   ground-breaking, inter alia because it finds more than twice as many   
   risk variants as previous studies have identified.   
      
   The term"genetic variants"means specific variations in the DNA code --   
   in this case, variants which are observed more frequently in people   
   with ADHD than in people without the diagnosis. Variants in DNA affect,   
   for example, the degree to which a gene is expressed and subsequently   
   the amount of protein that is encoded by the gene.   
      
   By linking the genetic variants -- i.e. the variations in DNA -- to   
   specific genes, the researchers have gained new knowledge about which   
   tissues and cell types are particularly affected in individuals with   
   ADHD. The study is based on data from the Danish iPSYCH cohort, deCODE   
   Genetics in Iceland and the Psychiatric Genomics Consortium.   
      
   Subsequently, the researchers combined the results with existing   
   data on gene expression in different tissues, cell types and brain   
   development stages, and they discovered that genes involved in ADHD have   
   a particularly high level of expression in a wide range of brain tissues   
   and early in brain development - - in fact already at the embryonic stage.   
      
   "This emphasises that ADHD should be seen as a brain developmental   
   disorder, and that this is most likely influenced by genes that have   
   a major impact on the brain's early development," says Professor Ditte   
   Demontis of the Department of Biomedicine at Aarhus University, who is   
   first author of the study.   
      
   In addition, the researchers found that the genetics that increase the   
   risk of ADHD particularly affect genes that are expressed in neurons,   
   especially dopaminergic neurons.   
      
   "This is interesting because dopamine plays a role in relation to the   
   reward response in the brain, and because a frequently used form of ADHD   
   medicine works by increasing the concentration of dopamine in different   
   brain regions.   
      
   Our results indicate that the imbalance in dopamine in the brains of   
   people with ADHD is partly attributable to genetic risk factors," says   
   Ditte Demontis.   
      
   Associated with reduced concentration capacity and short-term memory ADHD   
   is influenced by many common genetic variants, each of which increases   
   the risk slightly, says the professor.   
      
   In fact, with the help of advanced statistical models, the researchers   
   have estimated that there are around 7,300 common genetic variants that   
   increase the risk of ADHD. It is particularly interesting that the vast   
   majority of these variants -- 84-98 percent -- also have an influence   
   on other mental disorders, e.g. autism, depression and schizophrenia.   
      
   It has previously been shown that risk variants for ADHD can affect a   
   person's cognitive abilities.   
      
   To investigate this further, the researchers analysed data from an   
   independent dataset, consisting of 4,973 people who had undergone   
   extensive neuro-cognitive tests. By using information from the new   
   study about which variants increase the risk of ADHD, they found in   
   the independent data set that an increased load of ADHD risk variants   
   in the genome of an individual is associated with reduced reading and   
   mathematical abilities, reduced attention and reduced short-term memory.   
      
   "The results increase our knowledge of the biological mechanisms   
   underlying ADHD, and they point to specific genes, tissues and cell   
   types involved in ADHD. This knowledge can be used as a starting point   
   for further studies of the disease mechanisms and identification of new   
   drug targets," explains Ditte Demontis.   
      
   And the study must be followed up, she emphasises.   
      
   "We have only mapped a small fraction of the common variants that   
   influence ADHD -- just 27 of the 7,300 that potentially exist. So there   
   is a need for larger genetic studies," she says.   
      
   International cross-disciplinary collaboration is the way forward Large   
   international collaborations are crucial to identifying the genetic   
   causes of psychiatric diseases and neurodevelopmental disorders, because   
   to do so requires studies of tens or hundreds of thousands of people with   
   these conditions. Just as in the current ADHD study, there are often 100   
   or more researchers involved, with different areas of expertise, such   
   as genetics, psychiatry, psychology, epidemiology, molecular biology,   
   statistics, bioinformatics and computer science.   
      
   "In order to understand more of the genetic and biological mechanisms,   
   it is important to have even larger studies, involving more people with   
   ADHD," says Professor Anders Bo/rglum of the Department of Biomedicine,   
   Aarhus University, who is the last author of the study and one of the   
   research directors of the Danish iPSYCH project.   
      
   "But it is also important to undertake studies that focus on identifying   
   how the genetic risk variants perturb biological processes in the brain   
   cells (the neurons), and their way of joining up and communicating   
   with each other in the brain. For the latter, both brain cells and   
   early developmental stages of the brain, so-called mini-brainsor brain   
   organoids, are currently being examined" he says.   
      
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                   # Attention_Deficit_Disorder # Mental_Health_Research #   
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   ==========================================================================   
   Story Source: Materials provided by Aarhus_University. Original written   
   by Line Ro/nn. Note: Content may be edited for style and length.   
      
      
   ==========================================================================   
   Journal Reference:   
      1. Ditte Demontis, G. Bragi Walters, Georgios Athanasiadis, Raymond   
      Walters,   
         Karen Therrien, Trine Tollerup Nielsen, Leila Farajzadeh, Georgios   
         Voloudakis, Jaroslav Bendl, Biau Zeng, Wen Zhang, Jakob Grove,   
         Thomas D.   
      
         Als, Jinjie Duan, F. Kyle Satterstrom, Jonas Bybjerg-Grauholm,   
         Marie Baekved-Hansen, Olafur O. Gudmundsson, Sigurdur H. Magnusson,   
         Gisli Baldursson, Katrin Davidsdottir, Gyda S. Haraldsdottir,   
         Esben Agerbo, Gabriel E. Hoffman, So/ren Dalsgaard, Joanna Martin,   
         Marta Ribase's, Dorret I. Boomsma, Maria Soler Artigas, Nina   
         Roth Mota, Daniel Howrigan, Sarah E. Medland, Tetyana Zayats,   
         Veera M. Rajagopal, Alexandra Havdahl, Alysa Doyle, Andreas Reif,   
         Anita Thapar, Bru Cormand, Calwing Liao, Christie Burton, Claiton   
         H. D. Bau, Diego Luiz Rovaris, Edmund Sonuga- Barke, Elizabeth   
         Corfield, Eugenio Horacio Grevet, Henrik Larsson, Ian R.   
      
         Gizer, Irwin Waldman, Isabell Brikell, Jan Haavik, Jennifer   
         Crosbie, James McGough, Joanna Kuntsi, Joseph Glessner, Kate   
         Langley, Klaus-Peter Lesch, Luis Augusto Rohde, Mara H. Hutz,   
         Marieke Klein, Mark Bellgrove, Martin Tesli, Michael C. O'Donovan,   
         Ole Andreas Andreassen, Patrick W. L.   
      
         Leung, Pedro M. Pan, Ridha Joober, Russel Schachar, Sandra Loo,   
         Stephanie H. Witt, Ted Reichborn-Kjennerud, Tobias Banaschewski,   
         Ziarih Hawi, Mark J. Daly, Ole Mors, Merete Nordentoft, Ole   
         Mors, David M. Hougaard, Preben Bo Mortensen, Mark J. Daly,   
         Stephen V. Faraone, Hreinn Stefansson, Panos Roussos, Barbara   
         Franke, Thomas Werge, Benjamin M. Neale, Kari Stefansson, Anders   
         D. Bo/rglum. Genome-wide analyses of ADHD identify 27 risk loci,   
         refine the genetic architecture and implicate several cognitive   
         domains. Nature Genetics, 2023; DOI: 10.1038/s41588-022-01285-8   
   ==========================================================================   
      
   Link to news story:   
   https://www.sciencedaily.com/releases/2023/02/230209114741.htm   
      
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