We found an association between genetic ancestry and lung function among subjects who identified themselves as African American; specifically, the percentage of African ancestry was inversely associated with lung function in three independent cohorts across a wide range of ages. However, there were differences in the magnitude of the effect across the cohorts, possibly because of the older age of subjects in the HABC and CHS cohorts. The relative contribution of genetic ancestry is likely to be smaller among older persons who have had a greater cumulative exposure to environmental factors that adversely affect lung function.
Extrapolation of the distribution of percentage of African ancestry among the men and women in the CARDIA study to persons of the same sex and age group (18 to 34 years) suggests that for approximately 6.4% of persons in the United States who identify themselves as African Americans (i.e., 0.65 million persons, according to 2008 U.S. Census estimates)36
the percentage of African ancestry would be 15% higher or lower than the mean, suggesting they would be misrepresented by the use of standard race-based models. In these persons, the degree of misestimation of FEV1
could be greater than 122.1 ml in men and 83.1 ml in women, the equivalent of an age-associated loss of lung function of approximately 15 ml per year over a 5-to-8-year period.4
The inverse association between lung function and African ancestry may be especially important when predicted lung-function values are used to assess the severity of lung disease.35,37,38
Current clinical practice guidelines use the FEV1
:FVC ratio or percentages of predicted lung function in the assessment of the severity of chronic obstructive pulmonary disease (COPD),39,40
the severity of asthma,35
and the degree of overall lung impairment.41
Accordingly, inaccurate estimates of percentages of predicted lung function may result in the misclassification of disease severity and impairment.41
For example, an estimated 2.1 million self-identified African Americans have asthma.42
On the basis of the percentage of the predicted FEV1
value, the severity of the asthma would be misclassified for approximately 4% of these patients (i.e., 84,000 patients), were ancestry not taken into account. Misclassification of severity might affect even more patients with COPD, a condition more common than asthma. An improvement in the accuracy of predicted lung function may lead to more appropriate treatment for the level of impairment, resulting in more effective and efficient care.
There are some important limitations of our study. First, our analysis does not address population groups other than self-identified African Americans, such as Latinos, who have more complex patterns of ancestral admixture. Second, the association between lung function and ancestry found in our study may be the result of factors other than genetic variation, such as premature birth, prenatal nutrition, socioeconomic status, and other environmental factors.43,44
Third, we did not study a replication population with the same age range as that of the CARDIA cohort. Thus, we may have overestimated the association between ancestry and lung function in the CARDIA participants, who were young adults. Finally, some researcher groups used different statistical approaches to estimate ancestry in their respective study populations. We have found previously, however, that different approaches (e.g., Markov models and maximum-likelihood estimation) produce highly correlated results from the same set of markers.8,45
The consistency of our findings across three cohorts, despite the different methods for estimating ancestry, underscores the robustness of the association with ancestry.
In conclusion, our study shows that incorporating measures of individual genetic ancestry into normative equations of lung function in persons who identify themselves as African Americans may provide more accurate predictions than formulas based on self-reported ancestry alone. The same argument may apply to other ancestrally defined groups; further studies in this area are necessary. Further studies are also needed to determine whether estimates informed by genetic ancestry are associated with health outcomes. It remains to be seen whether differences associated with race or ethnic group in the response to medications that control asthma46,47
are more tightly associated with estimates of ancestry. Although measures of individual genetic ancestry may foster the development of personalized medicine, large clinical trials and cohort studies that include assessments of genetic ancestry are needed to determine whether measures of ancestry are more useful clinically than a reliance on self-identified race alone.