Hello there bloggies! Welcome to Science Sunday! Sorry for the tardiness in posting. We hit some ridiculous traffic on the way back from Maine! This is going to be a quick one, but I hope a nice little follow-up of last week’s post..

Last week, we discussed what a genome-wide association study or GWAS was. Check out that blog post here. There, I described that the genetic markers associated with disease in those studies are usually not casual or functional variants. The associated markers are simply tagging variation in the genome.

So, what is a causal variant? There are many different types of causal variants. Here are a few examples:

Genetic variant directly causes a disease

The most obvious type of casual genetic variant is one that directly causes a disease. That is, if a person has a certain genetic variant, you will almost certainly get a disease. Although, there is a concept called penetrance, but we will not dig into that topic today. Examples of this are Cystic Fibrosis and Huntington’s disease. These variants can also be described as pathogenic.

Genetic variant increases/decreases risk of a disease

Not all diseases with genetic components are caused by a single genetic variant or variants in a single gene. For many complex diseases, dozens of genes (or more!) collectively act to increase or decrease risk of a disease. Some of these are the common chronic diseases you hear about all the time are of this type, including Type 2 Diabetes, obesity, stroke, and heart attack. These variants are in no way deterministic. They simply contribute to disease along with the hundreds of other genetic variants that work within disease pathways.

Genetic variant influences biological function

Sometimes genetic variants are associated with disease, but only minutely influence one’s risk of disease (or protection from disease). This is actually what largely happens in GWAS. However, these findings can still have functional implications and reveal important biology underlying disease. For example, there could be enrichment of associated genes in various biological pathways or genetic variation in certain genomic areas can influence the activity/regulation of known genes. These variants require lots of clinical and wet-bench work in order to determine what implications these associations may have.

Determining whether an associated genetic variant is causal or functional is one of the hardest parts of a human geneticist’s job. Doing so usually requires loads more work than the initial studies that implicate various genetic variants. It becomes incredibly complicated and careful/consistent hypothesis testing.

Thank you all for stopping by Science Sunday! What do you think is needed to make a genetic variant causal or functional? Comment down below or on twitter @DrFsThoughts.

Thank you for bearing with this short and tardy post!

-Dr. F