title: Population stratification confounds genetic association studies among Latinos.
abstract: 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.
authors.affiliation: University of California, San Francisco, 94143-0833, USA.
authors.forename: Shweta
authors.initials: S
authors.lastname: Choudhry
authors.forename: Natasha E
authors.initials: NE
authors.lastname: Coyle
authors.forename: Hua
authors.initials: H
authors.lastname: Tang
authors.forename: Keyan
authors.initials: K
authors.lastname: Salari
authors.forename: Denise
authors.initials: D
authors.lastname: Lind
authors.forename: Suzanne L
authors.initials: SL
authors.lastname: Clark
authors.forename: Hui-Ju
authors.initials: HJ
authors.lastname: Tsai
authors.forename: Mariam
authors.initials: M
authors.lastname: Naqvi
authors.forename: Angie
authors.initials: A
authors.lastname: Phong
authors.forename: Ngim
authors.initials: N
authors.lastname: Ung
authors.forename: Henry
authors.initials: H
authors.lastname: Matallana
authors.forename: Pedro C
authors.initials: PC
authors.lastname: Avila
authors.forename: Jesus
authors.initials: J
authors.lastname: Casal
authors.forename: Alfonso
authors.initials: A
authors.lastname: Torres
authors.forename: Sylvette
authors.initials: S
authors.lastname: Nazario
authors.forename: Richard
authors.initials: R
authors.lastname: Castro
authors.forename: Natalie C
authors.initials: NC
authors.lastname: Battle
authors.forename: Eliseo J
authors.initials: EJ
authors.lastname: Perez-Stable
authors.forename: Pui-Yan
authors.initials: PY
authors.lastname: Kwok
authors.forename: Dean
authors.initials: D
authors.lastname: Sheppard
authors.forename: Mark D
authors.initials: MD
authors.lastname: Shriver
authors.forename: William
authors.initials: W
authors.lastname: Rodriguez-Cintron
authors.forename: Neil
authors.initials: N
authors.lastname: Risch
authors.forename: Elad
authors.initials: E
authors.lastname: Ziv
authors.forename: Esteban Gonzàlez
authors.initials: EG
authors.lastname: Burchard
mesh_terms: 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
chemical_list: D005819:Genetic Markers