NEJM -- Genetic Ancestry in Lung-Function Predictions

Genetic Ancestry in Lung-Function Predictions

Rajesh Kumar, M.D., Max A. Seibold, Ph.D., Melinda C. Aldrich, Ph.D., M.P.H., L. Keoki Williams, M.D., M.P.H., Alex P. Reiner, M.D., Laura Colangelo, M.S., Joshua Galanter, M.D., Christopher Gignoux, M.S., Donglei Hu, Ph.D., Saunak Sen, Ph.D., Shweta Choudhry, Ph.D., Edward L. Peterson, Ph.D., Jose Rodriguez-Santana, M.D., William Rodriguez-Cintron, M.D., Michael A. Nalls, Ph.D., Tennille S. Leak, Ph.D., Ellen O'Meara, Ph.D., Bernd Meibohm, Ph.D., Stephen B. Kritchevsky, Ph.D., Rongling Li, M.D., Ph.D., M.P.H., Tamara B. Harris, M.D., Deborah A. Nickerson, Ph.D., Myriam Fornage, Ph.D., Paul Enright, M.D., Elad Ziv, M.D., Lewis J. Smith, M.D., Kiang Liu, Ph.D., and Esteban González Burchard, M.D., M.P.H.


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.)


Source Information

From Children's Memorial Hospital (R.K.) and Northwestern University Feinberg School of Medicine (L.C., L.J.S., K.L.) — both in Chicago; National Jewish Health, Denver (M.A.S.); University of California at San Francisco, San Francisco (M.C.A., J.G., C.G., D.H., S.S., S.C., E.Z., E.G.B.); Henry Ford Health System, Detroit (L.K.W., E.L.P.); University of Washington, Seattle (A.P.R., E.O., D.A.N.); Pediatric Pulmonary Program of San Juan (J.R.-S.) and San Juan Veterans Affairs Medical Center, University of Puerto Rico School of Medicine (W.R.-C.) — both in San Juan; Laboratory of Neurogenetics (M.A.N.) and Laboratory of Epidemiology, Demography, and Biometry (T.B.H.), Intramural Research Program, National Institute on Aging, Bethesda, MD; Graduate School of Public Health, University of Pittsburgh, Pittsburgh (T.S.L.); College of Pharmacy (B.M.) and College of Medicine (R.L.), University of Tennessee Health Science Center, Memphis; Sticht Center on Aging, Wake Forest School of Medicine, Winston-Salem, NC (S.B.K.); School of Public Health, University of Texas Health Sciences Center at Houston, Houston (M.F.); and College of Public Health, University of Arizona, Tucson (P.E.).

Drs. Kumar, Seibold, Aldrich, and Williams contributed equally to this article.

This article (10.1056/NEJMoa0907897) was published on July 7, 2010, at NEJM.org.

Address reprint requests to Dr. Kumar at the Division of Allergy and Immunology, Children's Memorial Hospital, 2300 Children's Plaza, Box 60, Chicago IL 60614, or at rkumar@childrensmemorial.org.

open here to see the full-text:
NEJM -- Genetic Ancestry in Lung-Function Predictions