World Health Organisation ICD 11 on trans people

Just had another thought re. this..

They also looked a sex steroid metabolism genes in a population that could be treated with sex steroids. It’s a bit like saying that body builders on anabolic asteroids have changes and conveniently ignoring the facts the drugs they are taking cause them.

Actually, it isn't a potential problem for exome analysis. It would be if you were analysing RNA, but not for germline coding sequence. That's not going to be altered by taking sex steroids.

BowlofBabelFish
While I agree with most of your posts, I have to pick you up on your response to the abstract Wakame posted in support of genetic evidence for 'transness' (for want of a better word)

That paper is a fishing excercise. I’ve done loads of array work and it fails all the usual statistical checks.

It's not an array, it was exome sequencing, and as it's only an abstract (presumably for a talk or poster) I don't see how you can pass judgement on the statistical methodology without seeing more details.

An array is effectively a chip, with cut up bits of dna on. You get the RNA readout from a sample (which is all the actively genes that are being read and used) and turn it into DNA. Then you wash that over the chip and examine it. So a gene which is being highly expressed will have a stronger signal.

Exome analysis, which is what is described in that abstract, looks for variants or mutations in the germline and has nothing to do with RNA. The first grant I was principal investigator on did something similar.

Obviously you can look at different gene variants too - there are thousands of these variants between any two random people though so what you can’t do is just say look at ‘anything that comes up.’ Because if you fling enough spaghetti at the wall some will stick. 21000 genes, and a confidence level of 95% gives you roughly a thousand genes that will pop up as positive for chance just by chance. Ooops.

Obviously don't disagree with this.

So you have to be careful with arrays. There are very sophisticated analysis programs that allow you to reduce the false positives but by its nature an array is a fishing expedition. And that’s fine, as long as you then go into the source material and verify those gene changes and what they mean. So I’d then get actual tissue samples and look at whthervthat gene really was being expressed at a higher level. That paper didn't do that either - they stopped at the fishing.

One person's fishing expedition is another's unbiased, agnostic approach...
Yes, the data would need to be confirmed, but I don't think anyone is claiming it's anything but preliminary.

They also looked a sex steroid metabolism genes in a population that could be treated with sex steroids. It’s a bit like saying that body builders on anabolic asteroids have changes and conveniently ignoring the facts the drugs they are taking cause them.

Again, there are not enough details in the abstract to criticise the methodology. Yes, it's a potential problem, but it may or may not have been addressed.

As a geneticist (as I am also) I would be interested in your opinion on this paper www.ncbi.nlm.nih.gov/pubmed/22146048. I can only see the abstract (as I am no longer in academia and don’t have institutional access), but it seems fairly convincing to me that there is a genetic component to gender dysphoria. Maybe you can get the whole paper?

There are a couple of Twitter screenshots from a leading gender clinic in London and Spain boasting about how much money he was making. I don't think altruism is at the root of most private clinics

Stay safe, Birdbandit. Thinking of you.

Yes, if there were even the smallest hope for a non-surgical, non pharmaceutical-dependency-for-life option, surely it’s irresponsible to not ensure research is pursuing that possibility?

I worry that the best interests of transfolk aren’t the driving factor here. After all, there is much money to be made from all those prescriptions and surgical procedures - especially outside of the UK.

I can’t help but wonder if some gender therapists and surgeons have financial agreements over referrals :/

Finding an observable cause (as opposed to the felt-but-not-seen concept of gender identity) could actually safeguard vulnerable dysphoric people?

Right. I'm unclear why you're talking about it then.

STBXH was once such a happy and brilliant man, but is now so reduced. How can his anger and his shouting at me, because he has to have the pink toothbrush, how can this be can be considered an expression of his gender identity, and not a bit worrying.

The TRA argument for non medicalisation must be very frustrating for trans people who’d like to see more scientific research, not less of it. I feel for them.

If I had a condition where I thought my body was totally 'wrong', and the only 'solutions' being offered were major surgery and a reliance on medication for life, I would be hoping that research would be done to try to find less invasive solution: preferably one which would make me content with the body I have. When I have suggested that before, I have been told that that is either like trying to 'cure' homosexuality or that people tried this 50 years ago and it didn't work. As if science has not moved on at all in that time.

I have no need to take it up with them unless I’m a peer reviewer for their paper. In which case it’d have gone back to them with rather a lot of comments and queries.

There are no ‘genetic anomalies’ associated with being trans. None.

Do you not see, wakame that the demedicalisation of the trans ideology will result in defunding? Because if it’s no longer classed as an illness there will be no rationale to treat? That if you push for the idea of being able to define who is trans on brain scans, those will be used as a gatekeeping device?

What the trans lobby is trying to do with the science is contradictory. You can’t have it as a disorder but not a disorder, that you want an objective scan for but no you can self identify in to. It doesn’t work

Transition is not always an appropriate treatment. For minors for example itvis grossly unethical to use blockers and then go from there. Affirmative treatment is unethical when 80% of your patient population group won’t need it.

You haven't answered my question wakame.

And Thanks Bowl. I love your posts

Betty - I've had genetic counselling for a different inherited gene and the NHS were brilliant

The TRA argument for non medicalisation must be very frustrating for trans people who’d like to see more scientific research, not less of it. I feel for them.

I agree. The research community is being pressured to find ‘a gene for trans’ when they should be investigating dysphoria as a concept so that transpeople can access evidence based treatments that will benefit them. It worries me greatly that pressure is being on science this way and as we keep seeing, the genuinely vulnerable patient population with gender dysphoria will suffer for it.

Best of luck with the counselling. The NHS is amazing with it (disclaimer: I’m not a genetic counsellor as that has its own training pathway, I am a geneticist and scientist.)

"gender identity" is person's innate sense of their own sex.

So presumably you know what it is by looking in your underwear.

Thanks Babel!

I assumed that trans folk didn’t get referred to the genetic scientists, but I was prepared to be wrong (and would’ve loved to have looked at the research if it was a gene thing - I’ve been beyond impressed by both the staff at my local clinic and the worldwide body of work they are contributing to).

Regarding my outcome - I am trying to be stoic - I still have the exact same body as I had before we knew about the gene fault. The only thing that’s changed is we now have an option for additional knowledge and active risk management. I’m incredibly thankful for the NHS.

Knowledge about one’s own condition can be so useful for coming to terms with it. The TRA argument for non medicalisation must be very frustrating for trans people who’d like to see more scientific research, not less of it. I feel for them.

It doesn’t orchid
There aren’t any.

That paper is a fishing excercise. I’ve done loads of array work and it fails all the usual statistical checks.

An array is effectively a chip, with cut up bits of dna on. You get the RNA readout from a sample (which is all the actively genes that are being read and used) and turn it into DNA. Then you wash that over the chip and examine it. So a gene which is being highly expressed will have a stronger signal.
Obviously you can look at different gene variants too - there are thousands of these variants between any two random people though so what you can’t do is just say look at ‘anything that comes up.’ Because if you fling enough spaghetti at the wall some will stick.

21000 genes, and a confidence level of 95% gives you roughly a thousand genes that will pop up as positive for chance just by chance. Ooops.

So you have to be careful with arrays. There are very sophisticated analysis programs that allow you to reduce the false positives but by its nature an array is a fishing expedition. And that’s fine, as long as you then go into the source material and verify those gene changes and what they mean. So I’d then get actual tissue samples and look at whthervthat gene really was being expressed at a higher level. That paper didn't do that either - they stopped at the fishing.

They also looked a sex steroid metabolism genes in a population that could be treated with sex steroids. It’s a bit like saying that body builders on anabolic asteroids have changes and conveniently ignoring the facts the drugs they are taking cause them...

Do your research.

wakame As you have obviously been convinced by this research, can you point us in the direction of the most compelling studies so that we can all be as well informed as you?

Where in the WHO guidelines does it refer to genetic anomalies?

No Betty they don’t.

The BRCA2 gene variant you may or may not have is something you can counsel patients on. There are multiple studies, large bodies of work on it etc.

There is no current evidence that there’s ‘a trans gene’ at all. The current drive to get some sort of scientific ‘proof’ there is goes back to validation - there’s a need to say ‘look, it’s real! There’s a gene for it.’

It’s also very muddled because atcthe same time of course if you could identify a genetic signal associated with being trans you might be able to objectively say who was and who wasn’t and that idea is viciously rejected by activists. They also want descriptions of it in the medical literature changed to remove any reference to fetishism, transvestism and AGP (autogynephilia.) but again they do t want it totally demedicalised because then there’s no way to access treatment.

So the use and abuse of science is misguided and muddled.

I hope you get the all clear - if not, you will be able to access treatment and monitoring to reduce your chances of becoming ill in the future.

Do trans folk get referred to the genetic scientists then? I’ve found my personal journey into discovering our familial gene fault (BRCA2) to be fascinating (and terrifying). I’d love to learn about the trans experience - for instance, our fault line comes from the X chromosome, so it’s literally 50/50 as whether I have it, dependent on which X of my mother’s 2 XX’s I inherited.

I thought trans being genetic in origin had been ruled out via studies of identical twins though?