What are Genome-Wide Association Studies?

How to make use of these valuable genetic resources!

Julian Willett, MD, PhD

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Your average GWAS. Sourced from Howles et al. 2019, with paper available here.

Finding medical cures in your genes sounds too good to be true. Fortunately, there is a certain amount of truth in what geneticists, such as myself, can accomplish with the DNA sequences of people who selflessly contribute blood or cheek swabs for medical studies! While medical research typically takes years to produce a finding that makes it to a patient’s bedside (the new Alzheimer’s drug Leqembi took at least 18 years to complete development, counting the initial exploratory research), genetics research helps identify genes or proteins that could be medically targeted to offer relief to people with illness!

In this article, I will take you through how these analyses, termed genome-wide association studies (GWAS), can yield findings that help scientists and industry understand what drives disease and thus could represent promising candidates for drug development.

The Basics

Ultimately, GWAS for diseases like Alzheimer’s compares how much more frequently specific genetic variants occur in individuals with a disease than those without. While GWAS can also be done to evaluate health traits that are not classified as disease (such as height), focusing on this binary classification helps understand the foundation of the methods, evaluating the relationship between genetics and conditions.

Given that we are measuring association, statistics are naturally involved, which I will not go into much depth here to stay focused on the concepts. Statistical tests, such as chi-square tests or logistic regression, yield the p-values that link the probability of a specific genetic variant being associated with a trait. Association values that are deemed suggestive of a “true” association are those that are less than 5 x 10^-8.

One will often find several variants clustered together in a peak across the genome, making it more challenging to identify the single or subset of causal variants linked to the trait. One must use other tools, such as genetic fine-mapping, to clarify these signals, which can sometimes be pretty tricky.

How to Do a GWAS

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Julian Willett, MD, PhD

Loving husband. Physician scientist who enjoys spreading his knowledge and experiences with the world whether related to medicine, science, or his hobbies.