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Genome-wide association study identifies eight risk loci and implicates metabo-psychiatric origins for anorexia nervosa

Discussion in 'Other health news and research' started by Adrian, Jul 15, 2019.

  1. Adrian

    Adrian Administrator Staff Member

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    Given the recent blog by @Simon M on GWAS and ME and Chris Pontings interest I thought this article may interest some people. It looks at a GWAS study of anorexia nervosa

    https://www.nature.com/articles/s41588-019-0439-2.epdf?referrer_access_token=TA2-DphQcoeilsjFWbKRgtRgN0jAjWel9jnR3ZoTv0MH0rNWlH2E80DIwMDPjyTVthOmKtnDdgECvfBudW9wgr-OeYnh2xZ1hYFXCIUBwVPldCe2-QSMbrM2i4fH29ZUcv-b6Qjn_wHMYHAfjVxkPxdtPuA8FK9O26Jo7EVNRTS6I0D2xo0Rbz9-qVLGYESOSGAQxaHkkAvi44oaJivGSm6fnVQ0eUcyW2iaCqO6yZZaNSro2ZMi2bOKt3YeMlG4xbfUxSXUJanYDNxBNydWBT8p41WzeSgfjThdK84W1OA=&tracking_referrer=www.theguardian.com


    Abstract

    Characterized primarily by a low body-mass index, anorexia nervosa is a complex and serious illness1, affecting 0.9–4% of women and 0.3% of men2,3,4, with twin-based heritability estimates of 50–60%5.

    Mortality rates are higher than those in other psychiatric disorders6, and outcomes are unacceptably poor7.

    Here we combine data from the Anorexia Nervosa Genetics Initiative (ANGI)8,9 and the Eating Disorders Working Group of the Psychiatric Genomics Consortium (PGC-ED) and conduct a genome-wide association study of 16,992 cases of anorexia nervosa and 55,525 controls, identifying eight significant loci.

    The genetic architecture of anorexia nervosa mirrors its clinical presentation, showing significant genetic correlations with psychiatric disorders, physical activity, and metabolic (including glycemic), lipid and anthropometric traits, independent of the effects of common variants associated with body-mass index. These results further encourage a reconceptualization of anorexia nervosa as a metabo-psychiatric disorder. Elucidating the metabolic component is a critical direction for future research, and paying attention to both psychiatric and metabolic components may be key to improving outcomes.

    There was a guardian article as well

    https://www.theguardian.com/science...ot-just-a-psychiatric-problem-scientists-find
     
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  2. Adrian

    Adrian Administrator Staff Member

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    Interestingly the had a sample of 17000 cases.

    They found associations with Genes associated with metabolic processes.
     
  3. Andy

    Andy Committee Member

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    My prediction is that if they find a way to treat the metabolic part of the problem then it will solve it, no need to waste time on psychiatric rubbish once the actual cause has been sorted.
     
  4. Adrian

    Adrian Administrator Staff Member

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    Possibly. I've also seen people talk about the micro-biome with anorexia so it could be something in that that triggers genetically susceptible people.

    Something they point out in the guardian article is that they don't have a very good success rate for the psychiatric approaches.

     
  5. Hoopoe

    Hoopoe Senior Member (Voting Rights)

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    Correct me if I'm wrong. The negative correlations should be expected or are least unsurprising, considering that anorexia nervosa is defined by low body mass.

    gwas.jpg
    They also found some genes but how do we know that these genes aren't just the same information at the gene level?

    This doesn't seem to tell us much. It's only a hint of where to look further.
     
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  6. Marco

    Marco Senior Member (Voting Rights)

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    More (lighter) coverage :

    https://cosmosmagazine.com/biology/genetic-insight-into-anorexia-nervosa
     
  7. Hutan

    Hutan Moderator Staff Member

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    This study (or possibly an earlier version of it, also involving the University of North Carolina) was discussed on a PR thread here back in 2017, along with a wider discussion about causes of anorexia nervosa.

    In that thread I quoted the following from another study.

    Anorexia nervosa may prove to be another example showing that making incorrect assumptions that faulty thinking is a major causal factor of illness isn't harmless. It can reduce family support, disrupt the patient's relationship with medical professionals and greatly delay progress towards a better understanding of the illness. Psychologists need to be less hubristic and more scientific about the tools that they have.
     
  8. Esther12

    Esther12 Senior Member (Voting Rights)

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    Sorry - Missed this thread and started another. Will copy it over to here:

    Genetic findings in anorexia lead to questioning of link to perfectionism [Guardian article by the terrible Ian Sample]



    I've not looked at the original research (maybe this is over-hyped rubbish?!), and am just shutting down my PC, but thought this could be of interest in relation to Chalder's attempts to link CFS and eating disorders through claims about 'perfectionism'.

    Their headline:
    Anorexia not just a psychiatric problem, scientists find

    Excerpt:

    Doctors have long considered family environment to be a factor in anorexia nervosa, but in some cases even widely held beliefs might be mistaken. Perfectionism, for example, has been blamed as a cause of anorexia, but the latest work suggests it is the other way around.

    “The families of people with anorexia do tend to have higher levels of perfectionism in them, but we think people are getting cause and effect wrong. It’s not the perfectionism that’s causing the anorexia, it’s the tendency towards having anorexia that is causing the increased perfectionism,” said Breen. “What we think is happening is that the family environment and the genetics interact.”

    The eight genes identified in the research explain only a small fraction of anorexia. As with many medical conditions, there are likely to be hundreds or thousands of genes in total that contribute to a person’s risk of developing the disorder.
    Click to expand...
    I hate linking to the Guardian, but: https://www.theguardian.com/science...ot-just-a-psychiatric-problem-scientists-find
     
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  9. Amw66

    Amw66 Senior Member (Voting Rights)

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    Last edited: Jul 16, 2019
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  10. Amw66

    Amw66 Senior Member (Voting Rights)

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    This .
     
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  11. Jonathan Edwards

    Jonathan Edwards Senior Member (Voting Rights)

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    I have not had time to look in detail. However, I think you are right that the correlations in that graph are unsurprising - and the study is making use of that.

    What is surprising is that these correlated features appear to be at least in part genetically determined. Finding 'the same information at the gene level' is key because when genes are correlating they have to be causal. Which means that anorexia nervosa is not just due to psychological responses to emotional traumas or whatever.

    There is a caveat to genes being causal but it is unlikely to happen very often. For instance if a cultural pattern correlates with racial genes. We cannot say that tissue type genes found mostly in India cause people not to eat cows (or sephardic genes cause people to not eat pigs). That sort of thing is unlikely to apply here. Moreover, it seems that the linked genes do encode for tending to be thin - they are 'the same information at the gene level'. That pretty much has to be causal I think.
     
  12. Adrian

    Adrian Administrator Staff Member

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    And I think this is the point of doing a GWAS study in that it points to potential causal things (or at least things that predispose).
     
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  13. NelliePledge

    NelliePledge Moderator Staff Member

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    Yes it seems likely another one to add to the list

    ETA isn’t perfectionism another one that’s been used in CFS Cosmo quizzes , I mean psych research, too. I seem to remember wondering how that fits with malingering.
     
    Last edited: Jul 16, 2019
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  14. Jonathan Edwards

    Jonathan Edwards Senior Member (Voting Rights)

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    The genome itself is not influenced by environmental factors or life experiences. All these can do at best is change the methylation status of the genes for a generation or two. The nucleotide base code that genomics record is unchanged.

    The recent fashion for suggesting that environment and life experience can affect evolution is in fact bogus. What have been found are regulatory systems encoded genetically in DNA that allow for switching on and off of gene transcription not just within the lifetime of an adult organism but also within the gremlin across a longer period. It is the same as bamboo offcuts still knowing they should flower in 87 years time. Epigenetic regulation can cross a time frame longer than an individual. But it is all programmed in the genes. The responses are predetermined by the base sequences. New options require the usual random mutation and selection.
     
  15. duncan

    duncan Senior Member (Voting Rights)

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    Neuromuscular disease seems like a round hole for a round peg. There are several metabollic myopathies that might be potential candidates. That's where I'd put my money at this juncture. Many are genetic. Some of these kick in at birth, some at adolescence, some adult age.

    That someone had to endure being separated from their pet cat, or was forced to eat spinach at every Sunday meal, will fall to the wayside as just another psych tall-tale.
     
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  16. Mithriel

    Mithriel Senior Member (Voting Rights)

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    Hutan mentioned this "Before the 1960s people with anorexia nervosa did not give fear of getting fat as their reason for eating little. They said they were full, their stomach was upset, they were not hungry."

    This makes me think of me and CFS. There is a set of symptoms - not wanting to eat - but the patients, not just the doctors make sense of their symptoms in terms of the culture of the time.

    When we were told that fatigue was the main symptom of ME, after CFS was said to be the same thing, I felt that newly diagnosed people had the same symptoms as before but were interpreting it as fatigue rather than an abnormal response to exercise the way we had before CFS.
     
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  17. Jonathan Edwards

    Jonathan Edwards Senior Member (Voting Rights)

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    As I said, there is a recent fashion for getting muddled about this. I don't know what the genomics site is but it is probably commercial and will throw in anything that sounds trendy.

    People seem to think that if a methylation step crosses adult generations it is different from the methylation steps that cross cell generations within an adult - like lymphocyte maturation. But the mistake is to think that there is something special about the adult phase rather than the gamete and zygote phases.
     
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  18. James Morris-Lent

    James Morris-Lent Senior Member (Voting Rights)

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    The actual DNA sequence is preserved with great care. The error rate in cell division is quite low.

    Of course mutations build up over time, but different lines of cells will have different ones. An environmental mutagen could damage a lot of DNA, but affected cells would not be damaged uniformly.

    I imagine that they are really trying to refer to how gene expression is regulated. As JE referred to, this includes epigenetic modification of chromatin (the complex of DNA and proteins that 'package' the DNA) structure, which can be passed through generations of cells - and even whole organisms - and can be remodified. But the DNA sequence itself is not changed by this. It's quite well protected.

    There is no mechanism encoded by our genome that systematically modifies the genome. Quite the opposite.
     
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  19. Jonathan Edwards

    Jonathan Edwards Senior Member (Voting Rights)

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    The only caveat to that is that activation induced deaminase and related enzymes are encoded by or genome and they function to systematically, randomly and very infrequently modify the genome of the cell they are in. Whether germ line mutations are often due to this I do not know. In somatic mutation they very often are.
     
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  20. rvallee

    rvallee Senior Member (Voting Rights)

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    Perfectionism in psychosomatic research seems to play about the same role as aura in spiritual-based pseudosciences. It's that undefined thing that can be used to mean just about anything and can be "measured" to show just about anything you want, whichever direction a belief system needs it to play a role.

    It will be a watershed moment once the term disappears from the literature. As long as it's not replaced by some other vague concept to semantically abuse...
     
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