A genome-wide association study on African-ancestry populations for asthma.
BACKGROUND
Asthma is a complex disease characterized by striking ethnic disparities not explained entirely by environmental, social, cultural, or economic factors. Of the limited genetic studies performed on populations of African descent, notable differences in susceptibility allele frequencies have been observed.


OBJECTIVE
We sought to test the hypothesis that some genes might contribute to the profound disparities in asthma.


METHODS
We performed a genome-wide association study in 2 independent populations of African ancestry (935 African American asthmatic cases and control subjects from the Baltimore-Washington, DC, area and 929 African Caribbean asthmatic subjects and their family members from Barbados) to identify single-nucleotide polymorphisms (SNPs) associated with asthma.


RESULTS
A meta-analysis combining these 2 African-ancestry populations yielded 3 SNPs with a combined P value of less than 10(-5) in genes of potential biologic relevance to asthma and allergic disease: rs10515807, mapping to the alpha-1B-adrenergic receptor (ADRA1B) gene on chromosome 5q33 (3.57 x 10(-6)); rs6052761, mapping to the prion-related protein (PRNP) gene on chromosome 20pter-p12 (2.27 x 10(-6)); and rs1435879, mapping to the dipeptidyl peptidase 10 (DPP10) gene on chromosome 2q12.3-q14.2. The generalizability of these findings was tested in family and case-control panels of United Kingdom and German origin, respectively, but none of the associations observed in the African groups were replicated in these European studies. Evidence for association was also examined in 4 additional case-control studies of African Americans; however, none of the SNPs implicated in the discovery population were replicated.


CONCLUSIONS
This study illustrates the complexity of identifying true associations for a complex and heterogeneous disease, such as asthma, in admixed populations, especially populations of African descent.
Mathias
Rasika A
RA
Inherited Disease Research Branch, National Human Genome Research Institute, National Institutes of Health, Baltimore, MD, USA.
Grant
Audrey V
AV
Rafaels
Nicholas
N
Hand
Tracey
T
Gao
Li
L
Vergara
Candelaria
C
Tsai
Yuhjung J
YJ
Yang
Mao
M
Campbell
Monica
M
Foster
Cassandra
C
Gao
Peisong
P
Togias
A
A
Hansel
Nadia N
NN
Diette
Gregory
G
Adkinson
N Franklin
NF
Liu
Mark C
MC
Faruque
Mezbah
M
Dunston
Georgia M
GM
Watson
Harold R
HR
Bracken
Michael B
MB
Hoh
Josephine
J
Maul
Pissamai
P
Maul
Trevor
T
Jedlicka
Anne E
AE
Murray
Tanda
T
Hetmanski
Jacqueline B
JB
Ashworth
Roxann
R
Ongaco
Chrissie M
CM
Hetrick
Kurt N
KN
Doheny
Kimberly F
KF
Pugh
Elizabeth W
EW
Rotimi
Charles N
CN
Ford
Jean
J
Eng
Celeste
C
Burchard
Esteban G
EG
Sleiman
Patrick M A
PM
Hakonarson
Hakon
H
Forno
Erick
E
Raby
Benjamin A
BA
Weiss
Scott T
ST
Scott
Alan F
AF
Kabesch
Michael
M
Liang
Liming
L
Abecasis
Gonçalo
G
Moffatt
Miriam F
MF
Cookson
William O C
WO
Ruczinski
Ingo
I
Beaty
Terri H
TH
Barnes
Kathleen C
KC
D000328:Adult; D001741:Black or African American / Q000235:genetics; D001249:Asthma / Q000235:genetics*; D001460:Barbados; D044383:Black People / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D055106:Genome-Wide Association Study; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide