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Evaluation of self-reported ethnicity in a case-control population: the stroke prevention in young women study.

ABSTRACT: Population-based association studies are used to identify common susceptibility variants for complex genetic traits. These studies are susceptible to confounding from unknown population substructure. Here we apply a model-based clustering approach to our case-control study of stroke among young women to examine if self-reported ethnicity can serve as a proxy for genetic ancestry.A population-based case-control study of stroke among women aged 15-49 identified 361 cases of first ischemic stroke and 401 age-comparable control subjects. Thirty single nucleotide polymorphisms (SNPs) throughout the genome unrelated to stroke risk and with established ancestry-based allele frequency differences were genotyped in all participants. The Structure program was used to iteratively evaluate for K = 1 to 5 potential genetic-based subpopulations. Evaluating the population as a whole, the Structure output plateaued at K = 2 clusters. 98% of self-reported Caucasians had an estimated probability >/=50% of belonging to Cluster 1, while 94% of self-reported African-Americans had an estimated probability >/=50% of belonging to Cluster 2. Stratifying the participants by self-reported ethnicity and repeating the analyses revealed the presence of two clusters among Caucasians, suggesting that potential substructure may exist.Among our combined sample of African-American and Caucasian participants there is no large unknown subpopulation and self-reported ethnicity can serve as a proxy for genetic ancestry. Ethnicity-specific analyses indicate that population substructure may exist among the Caucasian participants indicating that further studies are warranted.

SUBMITTER: Mez JB

PROVIDER: S-EPMC2801514 | biostudies-literature | 2009 Dec

REPOSITORIES: biostudies-literature

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Evaluation of self-reported ethnicity in a case-control population: the stroke prevention in young women study.

Mez Jesse B JB Cole John W JW Howard Timothy D TD Macclellan Leah R LR Stine Oscar C OC O'Connell Jeffery R JR Wozniak Marcella A MA Stern Barney J BJ Sorkin John D JD Mitchell Braxton D BD Kittner Steven J SJ

BMC research notes 20091218

<h4>Background</h4>Population-based association studies are used to identify common susceptibility variants for complex genetic traits. These studies are susceptible to confounding from unknown population substructure. Here we apply a model-based clustering approach to our case-control study of stroke among young women to examine if self-reported ethnicity can serve as a proxy for genetic ancestry.<h4>Findings</h4>A population-based case-control study of stroke among women aged 15-49 identified ...[more]

PMID: 20021678

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Project description:BackgroundConflicting findings on the validity of self-reported stroke from existing studies creates uncertainty about the appropriateness of using self-reported stroke in epidemiological research. We aimed to compare self-reported stroke against hospital-recorded stroke, and investigate reasons for disagreement.MethodsWe included participants from the Australian Longitudinal Study on Women's Health born in 1921-26 (n?=?1556) and 1946-51 (n?=?2119), who were living in New South Wales and who returned all survey questionnaires over a defined period of time. We determined agreement between self-reported and hospitalised stroke by calculating sensitivity, specificity and kappa statistics. We investigated whether characteristics including age, education, area of residence, country of birth, language spoken at home, recent mental health at survey completion and proxy completion of questionnaire were associated with disagreement, using logistic regression analysis to obtain odds ratios (ORs) with 95% confidence intervals (CIs).ResultsAgreement between self-report and hospital-recorded stroke was fair in older women (kappa 0.35, 95% CI 0.25 to 0.46) and moderate in mid-aged women (0.56, 95% CI 0.37 to 0.75). There was a high proportion with unverified self-reported stroke, partly due to: reporting of transient ischaemic attacks; strokes occurring outside the period of interest; and possible reporting of stroke-like conditions. In the older cohort, a large proportion with unverified stroke had hospital records of other cerebrovascular disease. In both cohorts, higher education was associated with agreement, whereas recent poor mental health was associated with disagreement.ConclusionAmong women who returned survey questionnaires within the period of interest, validity of self-reported stroke was fair to moderate, but is probably underestimated. Agreement between self-report and hospital-recorded stroke was associated with individual characteristics. Where clinically verified stroke data are unavailable, self-report may be a reasonable alternative method of stroke ascertainment for some epidemiological studies.

Project description:BACKGROUND:Although cigarette smoking is a well-established risk factor for vascular disease, the genetic mechanisms that link cigarette smoking to an increased incidence of stroke are not well understood. Genetic variations within the genes of the inflammatory pathways are thought to partially mediate this risk. Here we evaluate the association of several inflammatory gene single nucleotide polymorphisms (SNPs) with ischemic stroke risk among young women, further stratified by current cigarette smoking status. METHODS:A population-based case-control study of stroke among women aged 15-49 identified 224 cases of first ischemic stroke (47.3% African-American) and 211 age-comparable control subjects (43.1% African-American). Several inflammatory candidate gene SNPs chosen through literature review were genotyped in the study population and assessed for association with stroke and interaction with smoking status. RESULTS:Of the 8 SNPs (across 6 genes) analyzed, only IL6 SNP rs2069832 (allele C, African-American frequency = 92%, Caucasian frequency = 55%) was found to be significantly associated with stroke using an additive model, and this was only among African-Americans (age-adjusted: OR = 2.2, 95% CI = 1.0-5.0, p = 0.049; risk factor adjusted: OR = 2.5, 95% CI = 1.0-6.5, p = 0.05). When stratified by smoking status, two SNPs demonstrated statistically significant gene-environment interactions. First, the T allele (frequency = 5%) of IL6 SNP rs2069830 was found to be protective among non-smokers (OR = 0.30, 95% CI = 0.11-.082, p = 0.02), but not among smokers (OR = 1.63, 95% CI = 0.48-5.58, p = 0.43); genotype by smoking interaction (p = 0.036). Second, the C allele (frequency = 39%) of CD14 SNP rs2569190 was found to increase risk among smokers (OR = 2.05, 95% CI = 1.09-3.86, p = 0.03), but not among non-smokers (OR = 0.93, 95% CI = 0.62-1.39, p = 0.72); genotype by smoking interaction (p = 0.039). CONCLUSION:This study demonstrates that inflammatory gene SNPs are associated with early-onset ischemic stroke among African-American women (IL6) and that cigarette smoking may modulate stroke risk through a gene-environment interaction (IL6 and CD14). Our finding replicates a prior study showing an interaction with smoking and the C allele of CD14 SNP rs2569190.

Dataset Information

Evaluation of self-reported ethnicity in a case-control population: the stroke prevention in young women study.

Publications

Evaluation of self-reported ethnicity in a case-control population: the stroke prevention in young women study.

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