Nancy Cox, PhD, Frontiers in Human Genetics Conference, October 11, 2024

How the Genetic Component to Laboratory Measurements in Medicine Can Degrade Outcomes and Add to Health Inequities: What Should We Do When the Genetics Adds Noise, Not Signal?

ABSTRACT

Like many quantitative biomarkers, about two-thirds of all commonly ordered laboratory values are significantly heritable. Lab values that have come into use more recently may be relatively specific indicators of disease risk, and these more recent labs may also be in the direct causal pathways to disease. LDL cholesterol is an example of this newer type of biomarker. The genetic component of LDL is predictive of atherosclerosis and cardiovascular disease; and the non-genetic factors that influence LDL levels are also predictive of these outcomes, because high LDL levels are causal related to the development of atherosclerosis and cardiovascular disease. Many of the older, long-established biomarkers are also quite heritable, but these biomarkers tend to be more non-specific indicators of a departure from healthy homeostasis. White blood cell counts may rise when people have infections and may fall when people take drugs that are toxic to white cells. But the genetic variation that influences interindividual variability in white cell counts does not predict whose counts will fall the most when they have chemotherapy, or whose counts will rise the most when they have appendicitis. For white cell counts and many other of the more traditional biomarkers, genetic variation contributing to the variability in these everyday lab values will sometimes be misleading for clinical decision-making. We will discuss some of the medical consequences of these challenges and show how removing the genetic component to the lab value can improve the bias and precision of the risk to disease that the lab values are intended to measure.