You asked for 'inheritable genetic physical diseases'. I gave you a list. Now it seems you actually want a list of 'mendelian' genetic disease, i.e. those which are caused by a single genetic variant.
Mendelian diseases are not the only sort of genetic disorder. This is a misunderstanding of genetics.
Source: I was a university researcher in psychiatric genetics
I'm making the distinction between illnesses that are directly caused by an identifiable genetic defect (e.g., Huntington's), and conditions that can arise when a certain combination of genes/genetic expressions are present but even then only arise some of the time.
As a professional in the field you'll know the terminology better than me and that's great, but you must understand the distinction I'm trying to make.
In the former case, we can clearly see a 1:1 causal link from genetic defect to the manifestation of the disease (whether it's a single gene or more is not central to the point).
In the latter case, the genetic predisposition is there, but there must also be some other form of conditional trigger.
One of your examples with which I'm quite familiar is asthma, which I've experienced at times in my life (though neither of my parents did).
I started experiencing it at about age 9 (as an allergic reaction to dust, dust mite and possibly other chronic infections I had at that age). Then it stopped in my mid teens. Then it started again when I smoked tobacco in my 20s, then stopped as soon as I stopped smoking. Then it started again in my mid 30s when I was experiencing severe stress and anxiety, then it stopped when I undertook a combination of approaches to reduce the stress/anxiety in my life, and a dietary program and other remedies to reduce chronic infections. That was 6 years ago and I've not needed asthma medication ever since.
The point is, there's nothing genetically deterministic about my asthma, given that it's come and gone through out my life and has been clearly influenced by environmental factors.
Further, it's plausible that the asthma has been a beneficial symptom, to protect my body from allergens and pathogens, and signal that I needed to change my lifestyle. Certainly, it was a big part of what signalled to me that I need to stop smoking, and later to clean up my diet and make other improvements to my emotional and physical health.
As I've proposed in several other comments, it's just as plausible that the conditions we regard as mental "illnesses" are likely not genetic flaws or other malfunctions at all, but rather beneficial adaptations that have been selected for by evolution (e.g., it's obvious how the presence of "ADHD" in a small percentage of the population would have been beneficial in prehistoric human tribes).
Given this, our real challenge is to do a better job of interpreting and responding to these conditions, as several practitioners going back decades have already figured out how to do.
If that works for you I don't want you get you of that view, but that seems to romanticize illnesses too much for my taste.
Almost every disease can be traced back to genes (as you said it doesn't matter how many of them). Of course how much those genes play a factor varies immensely based on many factors. And there absolutely is something genetically deterministic about your asthma - you just have found another way of shutting down the biochemical pathways that would normally lead you to have symptoms.
To anyone in research in the field, the distinction you are trying to make is moot. Huntington's is just as regulated as any of the "conditional diseases" you try to put in a separate category. Sure, it has a more deterministic ultimate fate, but it's gene expression likely varies by a lot of factors too, especially between different cell types. And with that exact differential view is how all diseases are studied.
You haven't said anything about being a qualified expert in the field, so I'll assume you're not - please correct me if otherwise.
> To anyone in research in the field, the distinction you are trying to make is moot
I wouldn't think this is true; it's about the most important distinction there could be in genetics - i.e., flaws/defects of specific genes vs traits/predispositions that have been selected for over the history of evolution.
If a trait has been selected for over tens/hundreds of thousands of years of evolution, it's a mistake to try and "cure" it; it's not something that can be cured, as it's there for an important reason. The right approach is to understand the conditions that trigger the symptoms, and create better conditions so the problem corrects, just as I've done.
> If that works for you I don't want you get you of that view, but that seems to romanticize illnesses too much for my taste.
This is an emotion-driven (and rather patronising) response, whereas I'm focused wholly on what is scientifically plausible and demonstrable.
I welcome new evidence to challenge the position I've put, but so far it hasn't been forthcoming.
> You haven't said anything about being a qualified expert in the field, so I'll assume you're not - please correct me if otherwise.
Not sure if that's enough qualification for you, but I'm a biochemistry undergrad with the goal of contributing to drug development in the future. The viewpoints I express here come from regularly reading recent papers related to mechanisms of various diseases, as well as what I've learned by talking to our professors and how we talk about diseases in class. (I also have an irrelevant background in software engineering, so I'm probably not as young and unexposed to the world as you might assume).
> If a trait has been selected for over tens/hundreds of thousands of years of evolution
That's simply not true that all (or even most of) our genes have been selected for "for tens/hundreds of thousands of years". Most diseases that occur after reaching reproductive age are not strongly selected for (this also holds true for animals). On top of that human social structures also help to weaken/circumvent evolutionary pressure.
> it's a mistake to try and "cure" it; it's not something that can be cured, as it's there for an important reason
> create better conditions so the problem corrects, just as I've done.
Not everything is there for an important reason. I'm lactose intolerant (also only attained after turning 18, so evading evolution). There is a long outdated evolutionary reason for turning of milk consumption in adults. There is not a good reason that applies in this day and age to turn of additional ways of energy supply to the body.
Yes, we do also look at the evolutionary circumstances of a gene in drug development, but that's mostly to reduce side effects by finding out what pathways could be connected.
I also don't see a big distinction between "curing" it "creating better conditions". Isn't curing it a way to create better conditions? Coming back to lactose intolerance, I can obviously always try to avoid lactose - or I can sometimes take lactase pills when it's easier in social situations.
> I'm focused wholly on what is scientifically plausible and demonstrable.
I'd like to see scientific evidence that bodies develop diseases to get people "to clean up their diet" or be introspective. Everything I see in terms of how individual biochemical pathways can be turned on/off without far reaching repercussions points into the opposite direction of us being so complex and interconnected that nothing should be tinkered with.
As I said I'm happy for you (honestly!), that this is how it worked out for you, but there are also a number of different events/experiences that could've lead you on the better path you are on now. No need for diseases to trigger that.
Also as a response to something you said in one of your other comments:
> Like so much in medical research, efforts are governed by what research will be funded, and ideally what will lead to the discovery of a drug or intervention that can generate billions of dollars of revenues. Those researchers who figured this stuff out decades ago don't need to be considered.
While this is of course true, that's not the only reason why the vast majority of people prefer taking medication for their diseases. People are lazy and changing habits is hard. For the same reason, it's most efficient (not effective!) to prescribe drugs to their patients, because they can't start lifestyle coaching every patient to change their diet.
Just look at cardiovascular diseases! It's been a leading cause of death for a long time, even though we know that improving levels of exercise and adjusting your diet can improve the odds a lot. This doesn't mean we shouldn't put money towards e.g. funding a drug that removes plaque from arteries.
I'll try to reply quickly, as I think we at least mostly understand each other, and it's time to sleep where I am.
> That's simply not true that all (or even most of) our genes have been selected for "for tens/hundreds of thousands of years". Most diseases that occur after reaching reproductive age are not strongly selected for (this also holds true for animals). On top of that human social structures also help to weaken/circumvent evolutionary pressure.
All the conditions we're talking about can very often express before reproduction happens; anxiety, depression, ADHD, bipolar, personality disorders, even schizophrenia (though that's later than most but still by the early 20s). And it's always been common for men to reproduce well into advanced age.
I gather you're arguing that mental "illness" hasn't actually been positively selected for by evolution, but in fact is just caused by crappy DNA that entered the gene pool by mistake and has stayed on for the ride.
It's a coherent claim, but doesn't really pass Occam's Razor.
For all the conditions I listed above, we can see how, in certain circumstances, they can be beneficial either to the individual or the group, so we don't need to conjure up an assumption that their emergence and persistence were undesirable accidents.
> I'm lactose intolerant
I'd be happy to research and debate this further at a later time if it turns out the topic materially hinges on this
> I also don't see a big distinction between "curing" it "creating better conditions". Isn't curing it a way to create better conditions?
It's a case of treating the symptoms vs the cause that pertain's to one's own life (their life experience and/or their environment).
Take the ADHD example. Current common treatment is to prescribe amphetamines. Future treatments according to this article might be to "switch off" the gene that causes ADHD-type behaviour. My "better conditions" approach is to look at the kid's overall personality and environment, investigate whether there's any trauma or distress underlying the behaviour (which is tragically often overlooked in the current treatment model), then once you've ensured the kid is in a safe and nurturing environment, if they're still hyperactive or unfocused, look at their whole personality and direct them towards activities that are suited to their talents and strengths (this happens sometimes but not nearly enough).
Using drugs or genetic treatments or anything else to "switch off" the ADHD is most likely to end up being somewhere between a lamentable underutilisation of talent/ability, and an egregious act of neglect/abuse.
When we treat genes as the "cause", we overlook so much in someone's life experience and environment that is highly controllable and that can have a far greater impact than by interfering with genes or biochemical pathways.
> I'd like to see scientific evidence that bodies develop diseases to get people "to clean up their diet" or be introspective.
The very existence of physical discomfort/pain or emotional distress is a demonstration of the biological signals we've developed to motivate changes to our conditions or behaviour.
We all know that eating too much of the wrong kind of food or drinking too much alcohol leads to physical and emotional pain/discomfort/distress that tells us to change.
Same goes for dysfunctional behaviour that leads to a relationship breakup or social rejection, leading to a period of introspection.
Sometimes the link between pain/illness and behaviour/environment is not so clear-cut, so we need to see a practitioner or do some research of our own.
But there's nothing in the least bit fringe or controversial about this concept.
> People are lazy and changing habits is hard
> we know that improving levels of exercise and adjusting your diet
I keep hearing this from experts on medicine and physiology. Some of them still dispute the "sugar is more harmful than fat" evidence (which I know is a separate issue that I don't want to start debating here/now).
I'm more optimistic about human potential.
People respond to incentives, and people will happily follow practices that clearly deliver benefits.
I know this from personal experience. I drank heavily, ate terribly, smoked and didn't stick to exercise. I tried doing everything mainstream health advocates recommended, but didn't get sustained results so I lost motivation and went back to bad old ways.
Then I found approaches that worked, and I've happily done them every day for over 8 years, because I've found that when I do, my life just keeps getting better.
Mendelian diseases are not the only sort of genetic disorder. This is a misunderstanding of genetics.
Source: I was a university researcher in psychiatric genetics