Population stratification confounds genetic association studies among Latinos View Full Text


Ontology type: schema:ScholarlyArticle     


Article Info

DATE

2006-01

AUTHORS

Shweta Choudhry, Natasha E. Coyle, Hua Tang, Keyan Salari, Denise Lind, Suzanne L. Clark, Hui-Ju Tsai, Mariam Naqvi, Angie Phong, Ngim Ung, Henry Matallana, Pedro C. Avila, Jesus Casal, Alfonso Torres, Sylvette Nazario, Richard Castro, Natalie C. Battle, Eliseo J. Perez-Stable, Pui-Yan Kwok, Dean Sheppard, Mark D. Shriver, William Rodriguez-Cintron, Neil Risch, Elad Ziv, Esteban Gonzàlez Burchard, Genetics of Asthma in Latino Americans (GALA) Study

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. More... »

PAGES

652-664

Identifiers

URI

http://scigraph.springernature.com/pub.10.1007/s00439-005-0071-3

DOI

http://dx.doi.org/10.1007/s00439-005-0071-3

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1046665577

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/16283388


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