BACKGROUND: Genetic association studies conducted in admixed populations may be confounded by population stratification resulting in spurious associations. The purpose of this pilot study was to determine the presence and effect of population stratification in a case-control study of brain arteriovenous malformation (BAVM). METHODS: We tested 83 ancestry informative markers in BAVM cases and healthy controls of self-reported Latino race/ethnicity (n = 294). Individual ancestry estimates (IAE) were obtained using the Structure program, assuming 3 underlying subpopulations. Summary chi(2) tests comparing genotype frequency of ancestry informative markers were used to detect stratification and IAE were included as covariates in logistic regression analysis to account for differences in genetic background. RESULTS: Admixture estimates for Latinos (overall 47% native American, 45% European and 8% African ancestry) revealed heterogeneity between individuals within ancestral groups. The summary chi(2) test was significant (p = 0.005), suggesting ancestral differences between cases and controls. Furthermore, genetic ancestry was associated with frequency differences in a promoter variant in the IL-6 gene (IL-6 -174G>C). On average, subjects with the IL6 -174 GG genotype had 6% greater Native American ancestry (p = 0.023). Age- and sex-adjusted risk of BAVM associated with the IL-6 -174 GG genotype was 1.85 (95% CI 0.99-3.48, p = 0.055), and further adjustments for IAE yielded an OR of 1.96 (95% CI 1.03-3.72, p = 0.039). CONCLUSION: The IL-6 -174G>C polymorphism was associated with increased risk of BAVM among Latinos after accounting for differences in ancestral background. These results suggest subtle, negative confounding and illustrate the importance of addressing population stratification in case-control studies conducted in admixed populations. Copyright 2008 S. Karger AG, Basel.
BACKGROUND: Genetic association studies conducted in admixed populations may be confounded by population stratification resulting in spurious associations. The purpose of this pilot study was to determine the presence and effect of population stratification in a case-control study of brain arteriovenous malformation (BAVM). METHODS: We tested 83 ancestry informative markers in BAVM cases and healthy controls of self-reported Latino race/ethnicity (n = 294). Individual ancestry estimates (IAE) were obtained using the Structure program, assuming 3 underlying subpopulations. Summary chi(2) tests comparing genotype frequency of ancestry informative markers were used to detect stratification and IAE were included as covariates in logistic regression analysis to account for differences in genetic background. RESULTS: Admixture estimates for Latinos (overall 47% native American, 45% European and 8% African ancestry) revealed heterogeneity between individuals within ancestral groups. The summary chi(2) test was significant (p = 0.005), suggesting ancestral differences between cases and controls. Furthermore, genetic ancestry was associated with frequency differences in a promoter variant in the IL-6 gene (IL-6 -174G>C). On average, subjects with the IL6 -174 GG genotype had 6% greater Native American ancestry (p = 0.023). Age- and sex-adjusted risk of BAVM associated with the IL-6 -174 GG genotype was 1.85 (95% CI 0.99-3.48, p = 0.055), and further adjustments for IAE yielded an OR of 1.96 (95% CI 1.03-3.72, p = 0.039). CONCLUSION: The IL-6 -174G>C polymorphism was associated with increased risk of BAVM among Latinos after accounting for differences in ancestral background. These results suggest subtle, negative confounding and illustrate the importance of addressing population stratification in case-control studies conducted in admixed populations. Copyright 2008 S. Karger AG, Basel.
Authors: Shweta Choudhry; Margaret Taub; Rui Mei; José Rodriguez-Santana; William Rodriguez-Cintron; Mark D Shriver; Elad Ziv; Neil J Risch; Esteban González Burchard Journal: Hum Genet Date: 2008-04-10 Impact factor: 4.132
Authors: Ludmila Pawlikowska; Mary N Tran; Achal S Achrol; Charles E McCulloch; Connie Ha; Denise L Lind; Tomoki Hashimoto; Jonathan Zaroff; Michael T Lawton; Douglas A Marchuk; Pui-Yan Kwok; William L Young Journal: Stroke Date: 2004-08-26 Impact factor: 7.914
Authors: Y Shu; C Brown; R A Castro; R J Shi; E T Lin; R P Owen; S A Sheardown; L Yue; E G Burchard; C M Brett; K M Giacomini Journal: Clin Pharmacol Ther Date: 2007-07-04 Impact factor: 6.875
Authors: Kirsten Neudoerffer Kangelaris; Anil Sapru; Carolyn S Calfee; Kathleen D Liu; Ludmila Pawlikowska; John S Witte; Eric Vittinghoff; Hanjing Zhuo; Andrew D Auerbach; Elad Ziv; Michael A Matthay Journal: Chest Date: 2011-12-29 Impact factor: 9.410
Authors: Rodney A Gabriel; Helen Kim; Stephen Sidney; Charles E McCulloch; Vineeta Singh; S Claiborne Johnston; Nerissa U Ko; Achal S Achrol; Jonathan G Zaroff; William L Young Journal: Stroke Date: 2009-11-19 Impact factor: 7.914
Authors: Sergio Avena; Marc Via; Elad Ziv; Eliseo J Pérez-Stable; Christopher R Gignoux; Cristina Dejean; Scott Huntsman; Gabriela Torres-Mejía; Julie Dutil; Jaime L Matta; Kenneth Beckman; Esteban González Burchard; María Laura Parolin; Alicia Goicoechea; Noemí Acreche; Mariel Boquet; María Del Carmen Ríos Part; Vanesa Fernández; Jorge Rey; Mariana C Stern; Raúl F Carnese; Laura Fejerman Journal: PLoS One Date: 2012-04-10 Impact factor: 3.240
Authors: Ludmila Pawlikowska; Jeffrey Nelson; Diana E Guo; Charles E McCulloch; Michael T Lawton; Helen Kim; Marie E Faughnan Journal: Mol Genet Genomic Med Date: 2018-03-06 Impact factor: 2.183
Authors: Laura M Huckins; Vesna Boraska; Christopher S Franklin; James A B Floyd; Lorraine Southam; Patrick F Sullivan; Cynthia M Bulik; David A Collier; Chris Tyler-Smith; Eleftheria Zeggini; Ioanna Tachmazidou Journal: Eur J Hum Genet Date: 2014-02-19 Impact factor: 4.246