Important Genes | Plus, understanding polygenic risk
When first getting started with understanding genetic variants (SNPs), it's easiest to think about one SNP = one effect. This is actually true for some genetic changes, especially for uncommon variants that have a large effect size.
I've updated my article on the top 10 genes to check in your genetic data. It's now a top 11 report. (I wanted to add one gene, but couldn't decide on which gene to kick off the island - so we end up with 11 instead of 10.)
These are all well-researched SNPs that have a fairly straightforward cause and effect. And they are ones that everyone should take a minute to check to see if they have them.
However, most genetic research is more complex than a simple one-to-one relationship. The rest of what's on Genetic Lifehacks and in the news about genetics is more nuanced, more murky, and dependent on multiple variables.
This is where polygenic risk scores come in. A polygenic risk score refers to adding up the SNPs that increase susceptibility and subtracting out the ones that are protective. I like polygenic risk analysis when it comes to research studies.
For individuals, knowing that they have multiple variables that increase the risk for heart disease or diabetes can help them understand where they may want to focus their health and wellness efforts. It's important to keep in mind, though, is that polygenic risk scores are just based on the SNPs that have been discovered so far. Most of the time, the polygenic risk algorithm only covers a part of the heritability of a condition. When you see reports that say you have X% risk of getting a disease, it's usually not as cut-and-dry as the numbers indicate. (And don't get me started on why I think choosing your baby based on a polygenic risk score is a slippery slope and bad science.)
There's a new genome-wide study out looking at the genetic risk associated with ME/CFS that kind of illustrates this point. The study identified 8 genetic locations that were associated with either a slight increase or slight decrease in the relative risk of ME/CFS. For an individual, this genetic information is not going to tell them much about why they have ME/CFS. However, from a big picture scientific point of view, the pathways involved -- particularly the immune response to viruses - are very interesting!
On Genetic Lifehacks, I try to focus more on the SNPs that have a larger impact, while still including the bigger picture of how genetic variants interact with other genes, lifestyle, and environmental factors. I don't provide scores or percentages because I think they give a people a false sense that the science is definitive. Polygenic studies and genome-wide studies are important, but they aren't always actionable at a personal level. Instead, they add to what we know about the mechanisms at play in a condition.
Stay curious!
Debbie
Top 11 Genes to Check in Your Genetic Raw Data
Getting started with learning about your genes can be overwhelming! Let me help you cut through the information overload. This guide offers a research-backed shortlist of genetic variants that can directly impact health and wellness.
Instead of overwhelming you with data, I’m focusing on 11 of the most clinically relevant genes that are found in 23andMe and AncestryDNA raw data. These are genes with robust research showing significant, actionable health risks or traits.
For each gene, you’ll learn:
Why it matters: A brief summary of its clinical importance
Which variants (SNPs) to look at: Members will see their genotypes right in the report, with highlighting to indicate a risk
Where to get more information: If you have a highlighted variant, you can find more details, including what to talk with your doctor about and possible natural solutions.
Read the rest of the article here
New on Longevity Lifehacks:
A gut metabolite that drives atherosclerosis, diabetes, and more
In this Longevity Lifehacks article, I go through the new study in Nature in which researchers in Spain found that a metabolite, imidazole propionate (ImP), produced by certain gut bacteria can cause atherosclerosis.
What I've been reading:
1. Clinical trial for long Covid, ME/CFS, and long Lyme
This new study involving lumbrokinase for post-viral and post-bacterial conditions is recruiting participants. Check it out if this applies to you.
(If you're wondering what the heck lumbrokinase is, here's my article on it.)
2. PFAS and phthalates in children's vitamins
This MAMAVATION article explains their latest lab results from testing different brands of children's vitamins for heavy metals, pesticides, PFAS, and phthalates. Luckily, heavy metals weren't much of a problem, but if you skip down to the "Not our favorite" section, you'll see that a couple of brands had higher phthalate levels than I would want to give to kids on a daily basis. (Just as a heads up - this website is one that I can't hardly look at without an ad blocker running.)
This is such a wonderfully succinct explanation of SNPs and polygenetic risk scores. We may understand the contours of the waves, but is so much to uncover, absorb, and make sense of.