Population stratification confounds genetic association studies among Latinos.
In the United States, asthma prevalence and mortality are the highest among Puerto Ricans and the lowest among Mexicans. Case-control association studies are a powerful strategy for identifying genes of modest effect in complex diseases. However, studies of complex disorders in admixed populations such as Latinos may be confounded by population stratification. We used ancestry informative markers (AIMs) to identify and correct for population stratification among Mexican and Puerto Rican subjects participating in case-control studies of asthma. Three hundred and sixty-two subjects with asthma (Mexican: 181, Puerto Rican: 181) and 359 ethnically matched controls (Mexican: 181, Puerto Rican: 178) were genotyped for 44 AIMs. We observed a greater than expected degree of association between pairs of AIMs on different chromosomes in Mexicans (P < 0.00001) and Puerto Ricans (P < 0.00002) providing evidence for population substructure and/or recent admixture. To assess the effect of population stratification on association studies of asthma, we measured differences in genetic background of cases and controls by comparing allele frequencies of the 44 AIMs. Among Puerto Ricans but not in Mexicans, we observed a significant overall difference in allele frequencies between cases and controls (P = 0.0002); of 44 AIMs tested, 8 (18%) were significantly associated with asthma. However, after adjustment for individual ancestry, only two of these markers remained significantly associated with the disease. Our findings suggest that empirical assessment of the effects of stratification is critical to appropriately interpret the results of case-control studies in admixed populations.
Choudhry
Shweta
S
University of California, San Francisco, 94143-0833, USA.
Coyle
Natasha E
NE
Tang
Hua
H
Salari
Keyan
K
Lind
Denise
D
Clark
Suzanne L
SL
Tsai
Hui-Ju
HJ
Naqvi
Mariam
M
Phong
Angie
A
Ung
Ngim
N
Matallana
Henry
H
Avila
Pedro C
PC
Casal
Jesus
J
Torres
Alfonso
A
Nazario
Sylvette
S
Castro
Richard
R
Battle
Natalie C
NC
Perez-Stable
Eliseo J
EJ
Kwok
Pui-Yan
PY
Sheppard
Dean
D
Shriver
Mark D
MD
Rodriguez-Cintron
William
W
Risch
Neil
N
Ziv
Elad
E
Burchard
Esteban Gonzàlez
EG
D000483:Alleles; D002874:Chromosome Mapping; D015986:Confounding Factors, Epidemiologic; D005787:Gene Frequency; D005819:Genetic Markers; D005828:Genetics, Population; D005838:Genotype; D006630:Hispanic or Latino / Q000235:genetics*; D006801:Humans; D008800:Mexico / Q000208:ethnology; D011647:Puerto Rico / Q000208:ethnology
D005819:Genetic Markers