Question about my risk

[Stavia]

hi Jack, welcome to the community.
I feel your pain - I don't understand the maths/statistics either.
My personal approach is just to know that I am at some unknown, personally unquantifiable, significantly higher magnitude of risk being an E4/4, and hence trying to live my life as positively as I can.
I don't believe that one can accurately predict an individual's risk from analyses of larger groups. Yes, there is a ballpark absolutely, but can one get any more accurate with what currently is, to be honest, pretty patchy genetic research with respect to outcomes?

However, there are many members who really find value in crunching the numbers. I hope they can come to your rescue!
I hope you enjoy and find value in our community.
Welcome again

[E4me]

I too recently learned about my E4/E4 from 23 and me. What's so surprising is that there is no family history whatsoever that I am aware of for AD. Does that "fact" have any significance for my personal risk profile, of would that be just trying to get some false comfort?

[Stavia]

E4me I would take comfort from that

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[SusanJ]

Hi E4me.

Maybe also look at your parent's lifestyle. Did they eat well? Exercise? Have good social connections? All these things work in one's favor and you could use those same strategies to your own benefit.

[WhatNext]

I'd like to second this quote from Jack:

"However, my understanding of DNA is superficial, the statistical formulas used in the studies are way over my head, I do not understand all of the jargon, and the even the parts of the studies ostensibly written in plain English rarely give up their meaning to me without a fight."

I'm in the same boat. Having a doctorate in mathematics makes me feel like I should be somewhat capable when statistics are involved, but there is so much jargon, combined with acronyms I don't understand, that I struggle to get anything out of it. So, that said...

In my early research after learning of my 3/4 status I stumbled across a formula for calculating my overall risk that consisted of multiplying the risk factors from every SNP associated with AD and then multiplying that result times the basic risk factor for a woman of European ancestry.

I no longer believe that's the correct way to assess risk, and the reason is because I don't have Crohn's disease. My Promethease report is riddled with risk factors for Crohn's. I have 22 SNPS related to it. Two of them are good: one SNP decreases risk by .77, the other says "normal risk". The other 20 SNPS increase risk. Two of them say "slightly increased risk" without an odds ratio, the others include odds ratios. If I multiply all of the odds ratios including the good one, I have 3,288x the normal risk of developing Crohn's disease. That's three thousand, two hundred eighty-eight.

It's estimated that 600,000 people in the US have Crohn's. Out of a population of 320 million, that's almost 18%. My multiplicative odds ratio multiplied by .18 is 592, giving me odds of 592 to 1 that I will develop Crohn's disease.

I've looked up the symptoms of Crohn's disease several times thinking I've missed something, but I simply do not have it. Onset is usually between 20 and 30 years of age; I just turned 65. I have less extreme but similar results for both type-1 and type-2 diabetes, psoriasis, and rheumatiod arthritis. I did not win the Promethease lottery.

Anyway my point is that given APOE status, I think other SNPs that increase risk are moot rather than risk being multiplicative.