• Researchers link 27 genetic variants to

    From ScienceDaily@1:317/3 to All on Thu Feb 9 21:30:24 2023
    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.

    * RELATED_TOPICS
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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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