Genetic ancestry in lung-function predictions.
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 (FEV(1)) 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 FEV(1)) 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.)
Kumar
Rajesh
R
Division of Allergy and Immunology, Children's Memorial Hospital, 2300 Children's Plaza, Box 60, Chicago IL 60614, USA. rkumar@childrensmemorial.org
Seibold
Max A
MA
Aldrich
Melinda C
MC
Williams
L Keoki
LK
Reiner
Alex P
AP
Colangelo
Laura
L
Galanter
Joshua
J
Gignoux
Christopher
C
Hu
Donglei
D
Sen
Saunak
S
Choudhry
Shweta
S
Peterson
Edward L
EL
Rodriguez-Santana
Jose
J
Rodriguez-Cintron
William
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Nalls
Michael A
MA
Leak
Tennille S
TS
O'Meara
Ellen
E
Meibohm
Bernd
B
Kritchevsky
Stephen B
SB
Li
Rongling
R
Harris
Tamara B
TB
Nickerson
Deborah A
DA
Fornage
Myriam
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Enright
Paul
P
Ziv
Elad
E
Smith
Lewis J
LJ
Liu
Kiang
K
Burchard
Esteban González
EG
D000293:Adolescent; D000328:Adult; D001741:Black or African American / Q000235:genetics*; D000368:Aged; D000369:Aged, 80 and over; D005260:Female; D005541:Forced Expiratory Volume / Q000235:genetics*; D005819:Genetic Markers; D005838:Genotype; D006801:Humans; D016014:Linear Models; D008297:Male; D008875:Middle Aged; D020411:Oligonucleotide Array Sequence Analysis; D012016:Reference Values; D012129:Respiratory Function Tests; D014797:Vital Capacity / Q000235:genetics*; D055815:Young Adult
D005819:Genetic Markers