Genetic Ancestry in Lung-Function Predictions

Abstract

BACKGROUND Self-identified race or ethnic group is used to determine normal reference standards in the prediction of pulmonary function. We conducted a study to determine whether the genetically determined percentage of African ancestry is associated with lung function and whether its use could improve predictions of lung function among persons who identified themselves as African American. METHODS We assessed the ancestry of 777 participants self-identified as African American in the Coronary Artery Risk Development in Young Adults (CARDIA) study and evaluated the relation between pulmonary function and ancestry by means of linear regression. We performed similar analyses of data for two independent cohorts of subjects identifying themselves as African American: 813 participants in the Health, Aging, and Body Composition (HABC) study and 579 participants in the Cardiovascular Health Study (CHS). We compared the fit of two types of models to lung-function measurements: models based on the covariates used in standard prediction equations and models incorporating ancestry. We also evaluated the effect of the ancestry-based models on the classification of disease severity in two asthma-study populations. RESULTS African ancestry was inversely related to forced expiratory volume in 1 second (FEV1) and forced vital capacity in the CARDIA cohort. These relations were also seen in the HABC and CHS cohorts. In predicting lung function, the ancestry-based model fit the data better than standard models. Ancestry-based models resulted in the reclassification of asthma severity (based on the percentage of the predicted FEV1) in 4 to 5% of participants. CONCLUSIONS Current predictive equations, which rely on self-identified race alone, may misestimate lung function among subjects who identify themselves as African American. Incorporating ancestry into normative equations may improve lung-function estimates and more accurately categorize disease severity. (Funded by the National Institutes of Health and others.)

Genome-wide genetic ancestry measurements to predict lung function in European populations

“…The mean absolute differences in predicted FEV1 observed between models with or without European ancestry were smaller than those observed in African Americans [5]. The French Canadian population is known to have less genetic heterogeneity than most general European populations [9].…”

“…Compared to self-reported race and/or ethnicity, genetic data can provide more accurate and objective measurements of ancestry and has the potential to alleviate some of the problems related to the lack of consensus on the definition of race and ethnicity worldwide [4]. A recent report suggested that genetically determined ancestry improves predicted lung-function measurements in African Americans [5]. Here, we test whether genetic ancestry derived from genome-wide genotyping data is useful to predict lung function in a diverse European population.…”

“…SNPs in linkage disequilibrium (r 2 o0.1) with any other SNP within a 50-SNP sliding window were excluded, resulting in a set of 59,767 autosomal SNPs entered in the ADMIXTURE program. As performed by KUMAR et al [5], we used genotypes from unrelated HapMap European and African populations as reference sets. HapMap reference set for Asian was also added, owing to the large proportion of this ethnic group in Vancouver.…”

Lung function, race and ethnicity: a conundrum

“…KUMAR et al [33] concluded that genetic variation affects lung volumes. In self-identified African Americans, in whom there is considerable ancestral admixture with genes from Europeans, they found a significant inverse association between lung function and African ancestry, but SES and environmental factors were not taken into account.…”

Lung function testing in children: importance of race and ethnic-specific reference equations

“…Ethnic differences in lung function were first reported over 150 years ago [4] and have been variously ascribed to differences in body physique, socioeconomic circumstances, environmental exposures and/or genetic ancestry [4][5][6][7][8][9][10]. Interpretation of these studies is complicated not only by differences in methodology, study population and sample size but by the complexities of defining 'race' or 'ethnicity' in an increasingly multiethnic society [4,6,7,11,12]. While self-identification remains the accepted standard for defining race and ethnicity, this rarely makes any adjustment for admixture (i.e., mixed parentage).…”