Abstract:
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.
journal_name
Neuroepidemiologyjournal_title
Neuroepidemiologyauthors
Kim H,Hysi PG,Pawlikowska L,Choudhry S,González Burchard E,Kwok PY,Sidney S,McCulloch CE,Young WLdoi
10.1159/000160215subject
Has Abstractpub_date
2008-01-01 00:00:00pages
224-8issue
4eissn
0251-5350issn
1423-0208pii
000160215journal_volume
31pub_type
杂志文章abstract::The incidence rate for primary intracranial neoplasms in the province of Trento (Italy) is 8.5/100,000/year, but the figures in the eleven administrative units ('comprensori') are different. The increased rates in C6 Val di Non and C10 Vallagarina are mainly due to the number of malignant tumors in the 45- to 64-year-...
journal_title:Neuroepidemiology
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更新日期:2007-01-01 00:00:00
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journal_title:Neuroepidemiology
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更新日期:1992-01-01 00:00:00
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journal_title:Neuroepidemiology
pub_type: 杂志文章
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更新日期:2000-07-01 00:00:00
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更新日期:2013-01-01 00:00:00
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更新日期:2018-01-01 00:00:00
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