Polygenic Risk Scores particularly for those under 50

This is interesting when many people are heart attack prone. Not all people with low or high scores are in the groups of no heart attack or a heart attack respectively.

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Certainly not with polygenic…there are well over 2,000 genetic polymorphisms that present some degree of increased risk when mixed with lifestyle choices, each other and the passage of time. But, increased risk certainly isn’t the cast iron gua-RON-tee that some folk may infer. Likewise, a person could have no genetic risk whatsoever and by their own efforts…overeating/oversitting/smoking etc…manage to present the same phenotype.

However, there are monogenic, autosomal dominant genetic causes of FH that do predict with near certainty. Very few but, oddly enough, a higher than average preponderance within the Netherlands…as I believe was outlined in a recent link to a Peter Attia podcast on this very topic. I’ll post it again for anyone interested…with the usual apologies about the paywall. I’ve had to listen a second time it was so informative and very technical and I am pretty sure that Attia’s guest gets into the nuts and bolts very quickly and, hopefully, before the teaser example cuts out.

And, just the usual caveat, we’re reading what’s basically a press release…as a quick Google will show (almost the exact script in other online outlets) Gina Kolata in NYT’s Tuesday Science supplement is as good as any stenographer, but just sayin’…

(other sources to try if one doesn’t have a NYT subscription)

Interesting fact about the Netherlands, I never would have guessed because there was a massive study done of men in both the Netherlands and an Indian village to compare the diabetes rate. The men a certain height and weight the Indian population were fattier. I do not remember what the study came up with “exactly” but a certain nutrient when a mother was pregnant in India was in shorter supply in the diet. The study went into enormous numbers of factors to find this as a cause for diabetes in that village’s population.

Google has buried the TV program discussing the study.

Instead I will leave you with this. It does not include the Netherlands for comparison but shows the difference in general.

But why include this (as interesting as it might be)?. The identified genotypes and phenotype of these Dutch families is unrelated to a side effect of T2D. They’re as likely as likely to develop the disease as someone carrying the genetic profile for, say, Tay-Sachs disease. These diseases are usually rare in the general population but much more prevalent in certain groups…primarily due to consanguinity/isolated gene pools etc.

This is one of the problems with diseases that are becoming routinely associated with “Lifestyle Choices”…it’s a bit too easy to forget that there are underlying genetic causes that can manifest themselves even for the best custodians of their body.

I was surprised by Holland having such a high rate of cardiac problems. That is why I included it because diabetes rates are much higher in India.

I have not forgotten the role of genetics. I did not know about the Dutch genetics in this case. It illustrates your points.

What always crosses my mind, when I read of a new “marker” being associated with something very expensive of a medical nature, is the insurance companies getting their hands on that information, and using it as an excuse to increase health insurance premiums for everyone who has that marker.

Maybe that marker will make it hard for people to get a “job”? I was more than a little concerned, when interviewing at Office Depot, when I was asked if I did bungee jumping, or sky diving, or anything else risky.

Steve

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Steve,

Yes those lines are getting more blurred. The law is clear the employer can not know of your conditions. Other than smoking and a few other things perhaps. The insurers have a problem they need to carry pools of the insured. They are regulated. They need to spread the risk. As employment comes and goes the insurers can not directly go to an employer and negotiate rates per employee. Other than a factor like smoking.

Well there are some very obvious “markers” for potential future healthcare costs that are blatantly obvious at interview. Any non smoking interviewer will surely be able to sniff out an interviewee that smokes…quite literally. Likewise excess bodyfat and the negative health implications that go with it. A bit tricky to do at a BMI of, say 26 or so…but a heck of a lot of folk are carrying a BMI of 30 or above.

A cynic would say “smoking” is merely the camel’s nose. The last place I worked did charge smokers more for their group health insurance. Why not charge people extra for living in the 'hood, as their chance of being shot is higher? Why not charge people extra for having a poor credit rating? Until the recent car insurance reform in Michigan, credit rating and neighborhood made a big difference in your car insurance rate.

When WPI went toes up, one of the warehouse guys applied at the last surviving Steelcase dealership. They rejected him, because he had a hernia, and had not had time to have it taken care of, before WPI turned out the lights.

Steve

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He never had to say he had hernia. Besides how do you know that is the reason? Did he decide that for himself? Or did a manager actually risk explaining that to him? It is illegal. Mangers do not explain such things. Granted if an exception needs to be made in the working conditions you are better off making mention of the problem. People hate hiring and then finding excuses. If they want you they will work with you. If they do not want you they wont bother with any excuses anyway. They will ghost you.

Redlining makes poor neighborhoods much power. It messes with the credit scores of actually good people who deserve credit and cant get it.

The odds of being shot are higher in rural areas than urban areas. Why should inner city people pay a price when rural people wont pay the price?

I can’t remember now how I learned of Hank’s rejection by the Steelcase dealer. That was early 2006. The dealer probably required a physical, especially for warehouse people that need to be capable of doing the work. The company I went to when WPI went toes up did hire Hank, and took care of the hernia.

I was wondering why he could not get it taken care of under COBRA.

…and personnel policies that might be illegal in other states, may be entirely legal here in fly-over country.

Steve

States could do the same for employers within the state. Employers with poor credit are required to pay more to each employee (due to the higher risk of the jobs going “poof” due to mismanagement, etc. Or is turnabout NOT “fair play”?

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So, once I slide down a rabbit hole of interest (“interest” of the fun and not-so-fun type) I have a hard time hauling myself out. I got to wondering about the relative prevalence of monogenic vs. polygenic associations with FH in the general population… and if it’d been studied (considering that the article in the OP and multiple other sources implied this was cutting edge stuff) Of course it has. Looks like I’m in the wrong place for early identification and primary prevention (as my intervention cardiologist actually mentioned at my last visit). Who knew🤔

Yep as my dad a well regarded doctor in his day would say at the end of the day the studies are a lot of crap. Dont waste your time they do not really apply and many will be contradictory within a few years.

You are trying too hard but that is up to you.