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Keywords:

  • African Americans;
  • African ancestry;
  • fibrinogen;
  • genetic admixture;
  • Hispanics;
  • plasmin–antiplasmin

Abstract

  1. Top of page
  2. Abstract
  3. Introduction
  4. Methods
  5. Results
  6. Discussion
  7. Acknowledgements
  8. Disclosure of Conflict of Interests
  9. References
  10. Supporting Information

Summary. Background: Epidemiologic studies report that self-identified African Americans typically have higher hemostatic factor levels than do self-identified Caucasians or Hispanics.Objective: To enhance understanding of phenotypic variation in hemostatic factor levels by race/ethnicity, we evaluated the relationship between genetic ancestry and hemostatic factor levels among Multi-Ethnic Study of Atherosclerosis (MESA) study participants.Patients/methods: Our sample included 712 African American and 701 Hispanic men and women aged 45 to 84 years. Individual global ancestry was estimated from 199 genetic markers using STRUCTURE. Linear regression models were used to evaluate the relationship between ancestry and hemostatic factor levels, adjusting for age, gender, education, income and study site.Results: Among African Americans, mean ± standard deviation (SD) ancestry was estimated as 79.9% ± 15.9% African and 20.1% ± 15.9% European. Each SD (16%) greater African ancestry was associated with 2.1% higher fibrinogen levels (= 0.007) and 3.5% higher plasmin–antiplasmin (PAP) levels (= 0.02). Ancestry among African Americans was not related to levels of factor (F)VIII or D-dimer. Mean ± SD estimated ancestry among Hispanics was 48.3% ± 23.8% Native American, 38.8% ± 21.9% European, and 13.0% ± 8.9% African. In Hispanics, each SD (19%) greater African ancestry was associated with 2.7% higher fibrinogen levels (= 0.009) and 7.9% higher FVIII levels (= 0.0002). In Hispanics, there was no relation between African ancestry and D-dimer or PAP levels, or between European ancestry and hemostatic factor levels.Conclusions: Greater African ancestry among African Americans and Hispanics was associated with higher levels of several hemostatic factors, notably fibrinogen. These results suggest that genetic heterogeneity contributes, albeit modestly, to racial/ethnic differences in hemostatic factor levels.


Introduction

  1. Top of page
  2. Abstract
  3. Introduction
  4. Methods
  5. Results
  6. Discussion
  7. Acknowledgements
  8. Disclosure of Conflict of Interests
  9. References
  10. Supporting Information

We recently reported that in the Multi-Ethnic Study of Atherosclerosis (MESA), racial/ethnic variation in hemostatic factor levels [1] coincided with rank ordering of cardiovascular disease (CVD) risk across racial/ethnic groups [2]. African Americans generally had the most thrombogenic profile, followed by Hispanic and Caucasian participants with similar levels, and then Chinese participants [1]. For example, among female MESA participants percent factor (F)VIII was 185 among African Americans, 166 among Hispanics, 162 among Caucasians and 159 among Chinese. Results were similar for men. The MESA findings are in accordance with results reported by others [3–12]. In MESA, adjustment for socio-economic, lifestyle and physiologic characteristics did not fully explain racial/ethnic differences in levels of hemostatic factors, suggesting that there may be racial/ethnic-specific genetic determinants that contribute to the observed racial/ethnic differences. Conferring additional support for this concept, genetic variants have been identified that influence hemostatic factor levels, and racial/ethnic differences in frequencies of these variants exist [7,13,14].

In the US there has been significant admixture among racial/ethnic groups creating populations with multiple ancestral backgrounds. In these admixed populations, estimates of individual global ancestry can be obtained using a series of genetic markers, termed ancestry informative markers, known to have substantial allele frequency differences between ancestral populations. Individual global ancestry quantifies the proportion of an individual’s ancestors who came from a specific ancestral population [15], and thus is a measure of genetic admixture. Previous work has found genetic admixture to be related to several CVD risk factors [16–20], subclinical CVD [21,22] and clinical CVD [23,24].

Little is presently known about whether genetic ancestry is associated with hemostatic factor levels. Using individual ancestry estimates for MESA African Americans and Hispanics, we tested the hypothesis that greater African ancestry would be associated with higher hemostatic factor levels. Results from the present study offer insights into whether racial/ethnic differences in hemostatic factor levels are a consequence of genetic ancestry.

Methods

  1. Top of page
  2. Abstract
  3. Introduction
  4. Methods
  5. Results
  6. Discussion
  7. Acknowledgements
  8. Disclosure of Conflict of Interests
  9. References
  10. Supporting Information

Study population

MESA is a prospective epidemiologic cohort which began in July 2000 [25]. In total, 6814 men and women between the ages of 45 and 84 years, all free of clinical CVD at baseline, were recruited in six US field centers. Participants were classified as Hispanic, non-Hispanic African American, non-Hispanic Caucasian or non-Hispanic Chinese on the basis of their responses to questions on race, ethnicity and nationality that were modeled after the 2000 US census. African American participants were recruited from Forsyth County, NC; Chicago, IL; New York, NY; Baltimore, MD; and Los Angeles, CA. Hispanic participants were recruited from Saint Paul, MN; New York, NY; and Los Angeles, CA. Local institutional review committees approved the MESA protocol, and all participants gave informed consent.

From participants who gave informed consent for genetic analyzes, a subsample of 2847 MESA participants was randomly selected within self-reported racial/ethnic groups for a candidate gene study that included 712 African American, 705 Hispanic, 718 Chinese and 712 Caucasian participants and approximately equal numbers of men and women. In general, Chinese groups and Caucasians of Northern European descent, such as those in MESA, show very little admixture with other populations (< 5%); hence, the present study concentrates only on estimating ancestry and examining associations with hemostatic factors in the African American and Hispanic groups.

Individual ancestry estimates

Our analyzes utilize individual ancestry estimates previously created in MESA by Wassel et al. [21]. Briefly, 199 ancestry informative markers were chosen to maximize allele frequency differences between ethnic groups, and were genotyped in the MESA candidate gene subsample in two separate panels: Panel 1 included 96 ancestry informative markers selected from an Illumina SNP database to maximize differences in allele frequencies between Caucasian and African, Caucasian and Chinese, or African and Chinese groups; Panel 2 included an additional 103 ancestry informative markers informative for Hispanic ancestry, which were selected from published lists to be informative for Hispanic ancestry [26,27]. A full listing of ancestry informative markers, together with minor allele frequencies among the four MESA racial/ethnic groups, has been published previously (see Wassel et al. [21] Table S1). Illumina Genotyping Services (Illumina, Inc., San Diego, CA, USA) performed genotyping using the GoldenGate assay. Standard quality control criteria were employed. Individual ancestry estimates were created from these ancestry informative markers using STRUCTURE version 2.2 software, which employs a Bayesian Markov Chain Monte Carlo simulation approach. STRUCTURE was selected as in ‘information rich’ scenarios (i.e. where pseudo-ancestral groups are relatively large and markers are, overall, highly informative), such as this, it performs similarly to other software programs such as ADMIXMAP, as well as frequentist maximum likelihood approaches. Furthermore, STRUCTURE has the added benefit of being able to model the linkage disequilibrium between ancestry informative markers, and thus can handle situations where these markers are not independent.

Individual ancestry estimates were obtained in STRUCTURE by utilizing pseudoancestral population genotype data obtained from HapMap (60 Yoruban Nigerians) and previous genotype data collected on 345 individuals from Native American populations [27]. The 712 MESA Caucasians were also used as pseudoancestors [21]. In determining the appropriate K (i.e. number of populations) for both the African American and Hispanic groups, K was varied between 1 and 5 with multiple iterations per K. A K of 2 was deemed most appropriate for African Americans, whereas a K of 3 was most appropriate for the Hispanic group [21]. Additional details on ancestry estimation in MESA have been reported previously [21].

Hemostatic factor assessment

Levels of baseline fibrinogen, factor (F)VIII, D-dimer and plasmin–antiplasmin (PAP) were measured on the full MESA cohort at the Laboratory for Clinical Biochemistry Research (University of Vermont, Burlington, VT, USA). Fibrinogen was measured using a BN™II nephelometer (N Antiserum to Human Fibrinogen; Dade Behring Inc., Deerfield, IL, USA); the inter-assay CV was 2.6%. FVIII coagulant activity was assessed using the Sta-R analyzer (STA-Deficient VIII; Diagnostica Stago, Parsippany, NJ, USA); the inter-assay CV was 8.8% to 14.6%. D-dimer was measured by immuno-turbidometric methods on the Sta-R analyzer (Liatest D-DI; Liatest VWF; Diagnostica Stago); the inter-assay CV ranged from 5.8% to 18.6%. PAP was measured using a two-site ELISA that utilizes two monoclonal antibodies; the inter-assay CV was 6.7 to 11.1%. Laboratory technicians were blinded to the race/ethnicity of the samples.

Additional covariates

Age, gender, education, income, smoking status, current alcohol use, body mass index, statin use and the use of postmenopausal hormones (hormone replacement therapy [HRT]) were self-reported. The leisure physical activity score was computed as the sum of metabolic equivalent min per week of active behaviors [28]. Prevalent diabetes was defined by the use of diabetes medications or fasting glucose of ≥ 126 mg dL–1. Hypertension was defined as diastolic blood pressure ≥ 90 mmHg, systolic blood pressure ≥ 140 mmHg or a self-reported history of hypertension and use of hypertensive medications.

Statistical analysis

After excluding participants taking warfarin at baseline (0 African American, 4 Hispanics and 4 Caucasians), our final analytic sample included 712 African Americans, 701 Hispanics and 708 Caucasians. For the primary analysis, hemostatic factor distributions were log transformed and geometric means were reported. Although fibrinogen and FVIII were not skewed, we elected to log transform these variables as doing so did not impair model fit or stability, and it permitted use of a consistent outcome (percent difference) and direct comparison of results across biomarkers.

Means and frequencies of unadjusted covariates and hemostatic factors are reported, stratified by race/ethnicity. Linear regression was used to assess the percent difference (95% confidence interval [CI]) in hemostatic factor levels per standard deviation (SD) increase in African ancestry among African Americans, and in European and African ancestry among Hispanics. The African Americans and Hispanics were modeled separately. As only K-1 ancestry estimates are needed to fully describe ancestry if K populations are assumed, we simultaneously include European and African ancestry estimates as continuous variables in the Hispanic models, while not including Native American ancestry estimates in the models. For African Americans, we included African ancestry in the models, omitting European ancestry.

Staged models were employed with the first model adjusting for demographic characteristics, including age, gender, education, income and field site. Our second model additionally controlled for the following major CVD risk factors: current smoking, current alcohol use, body mass index, leisure physical activity, diabetes status, hypertension status, statin use and a three-level variable modeling gender and HRT use (i.e. men, women not on HRT and women on HRT) in lieu of a dichotomous gender variable. Additive interactions of the admixture and hemostatic factor relations by gender and socioeconomic status were assessed. Detectable percent differences per SD of African ancestry at 80% power, and alpha of 0.05 are shown in Table S1. We had reasonable power (80%) to detect percents that are small (i.e. 1.5–5.0%) for all of the hemostatic markers, with possibly the exception of D-dimer which is more in the 10% range.

Restricted cubic spline models were used to graphically depict the relation between African ancestry and select hemostatic factors, adjusted for demographic characteristics. Among MESA African Americans, the distribution of African ancestry was sparse for ancestry proportions below 0.5 (n = 39). Therefore, we conducted the spline analysis on African Americans with percent of African ancestry ≥ 0.5. Analogously, among MESA Hispanic Americans very few had African ancestry proportions higher than 0.5 (n = 44). Thus, analyzes for MESA Hispanic participants were restricted to those with a proportion of African ancestry ≤ 0.5. The natural scale was used for spline analyzes, unless otherwise noted.

Results

  1. Top of page
  2. Abstract
  3. Introduction
  4. Methods
  5. Results
  6. Discussion
  7. Acknowledgements
  8. Disclosure of Conflict of Interests
  9. References
  10. Supporting Information

Characteristics of MESA participants selected for the MESA candidate gene sub-study, stratified by self-reported racial/ethnic group, are presented in Table 1. Consistent with our previous manuscript [1] which used data from the entire MESA cohort, self-reported race/ethnicity was associated with hemostatic factor levels among substudy participants. Relative to Caucasians, African Americans had 6.5% higher geometric mean fibrinogen (355 vs. 333 mg dL–1; < 0.0001), 10.1% higher FVIII (162 vs. 147%; < 0.0001), 18.8% higher D-dimer (0.26 vs. 0.22 μg mL–1; = 0.0006) and 5.7% higher PAP (4.66 vs. 4.41 nm; = 0.009), after adjustment for age, sex, education, income and site. As compared with Caucasians, Hispanics had 3.5% higher geometric mean fibrinogen levels (345 vs. 333 mg dL–1; < 0.0001), but similar levels of FVIII (149 vs. 147%; = 0.60), D-dimer (0.20 vs. 0.22 μg mL–1; = 0.18) and PAP (4.27 vs. 4.41 nm; = 0.21), after adjusting for demographic variables.

Table 1.   Unadjusted baseline characteristics among self-identified Caucasian, African American and Hispanic participants of the Multi-Ethnic Study of Atherosclerosis Candidate Gene Study: 2000–2002
 CaucasianAfrican AmericanHispanic
= 708= 712= 701
  1. *MET, work metabolic rate/resting metabolic rate; 1 MET = 3.5 mL kg–1 h–1. Natural log. Geometric mean.

Demographics
 Age, years ± SD61.5 ± 10.461.5 ± 9.961.1 ± 10.2
 Male, n (%)329 (46.5)321 (45.1)321 (45.8)
 Education, n (%)
  < High school diploma33 (4.7)91 (12.9)318 (45.4)
  High school or some college323 (45.8)395 (55.9)317 (45.2)
  College degree350 (49.6)221 (31.3)66 (9.4)
 Income, n (%)
  < $20K68 (9.8)131 (19.7)285 (42.0)
  $20K to < $50K226 (32.6)273 (41.1)276 (40.7)
  ≥ $50K400 (57.6)260 (39.2)118 (17.4)
Behaviors
 Smoked within past 30 days, n (%)112 (15.8)135 (19.0)105 (15.0)
 Leisure physical activity, mean MET* min per week ± SD2651 ± 30212817 ± 33312064 ± 2545
 Alcohol, current use, n (%)517 (79.7)344 (58.0)337 (64.1)
 HRT, current use, n (%)164 (49.6)101 (28.9)76 (21.8)
 Statins, current use, n (%)97 (13.7)113 (15.9)96 (13.7)
Physiologic characteristics
 Body mass index, kg m–2 ± SD27.8 ± 5.330.1 ± 5.829.5 ± 5.0
 Diabetes, n (%)46 (6.5)119 (16.8)118 (16.8)
 Hypertension, n (%)276 (39.0)398 (55.9)292 (41.7)
 Ln Fibrinogen ± SD5.79 ± 0.215.86 ± 0.215.87 ± 0.20
 Fibrinogen, mg dL–1328351355
 Ln Factor VIII ± SD4.97 ± 0.425.09 ± 0.435.02 ± 0.39
 Factor VIII, %144163151
 Ln D-dimer ± SD−1.56 ± 0.91−1.37 ± 0.99−1.50 ± 0.90
 D-dimer, μg mL–10.210.260.22
 Ln Plasmin-antiplasmin ± SD1.48 ± 0.381.54 ± 0.401.46 ± 0.37
 Plasmin–antiplasmin, nm4.374.674.32

Among self-identified African Americans, mean ± SD ancestry was estimated as 79.9% ± 15.9% African and 20.1% ± 15.9% European. After adjustment for demographic factors (age, sex, education, income and field site), greater African ancestry (per 1 SD, or 16%) was associated with 2.12% (95% CI: 0.58%, 3.64%) higher fibrinogen levels and 3.49% (95% CI: 0.61%, 6.29%) higher PAP levels, whereas there was no relationship between ancestry and levels of factor VIII or D-Dimer (Table 2). The results were similar with additional adjustment for behaviors and physiologic characteristics. Utilizing results from a cubic spline model, Fig. 1 provides a visual depiction of the relationship between African ancestry and levels of fibrinogen and PAP among African Americans, with adjustment for demographic characteristics.

Table 2.   Percent difference in hemostatic factor levels per 1 standard deviation*† greater African ancestry among 712 self-identified African Americans: Multi-Ethnic Study of Atherosclerosis Candidate Gene Study 2000–2002
 % Difference (95% CI)P-value
  1. *1 standard deviation = 15.9%. Adjusted for age, gender, education, income and field site.

Fibrinogen2.12 (0.58, 3.64)0.007
Factor VIII0.02 (−3.45, 3.37)0.99
D-Dimer−0.15 (−7.65, 6.83)0.97
PAP3.49 (0.61, 6.29)0.02
image

Figure 1.  Association of African ancestry with mean [95% confidence interval (CI)] fibrinogen (panel A) and plasmin–antiplasmin levels (panel B) among 704 self-identified African Americans*: MESA 2000–2002. *Adjusted for age, gender, education, income and field site. Geometric mean.

Download figure to PowerPoint

Mean ± SD estimated ancestry in self-identified Hispanics was 48.3% ± 23.8% Native American, 38.8% ± 21.9% European and 13.0% ± 18.9% African. Each SD (19%) greater African ancestry was associated with 2.73% (95% CI: 0.68%, 4.82%) higher fibrinogen levels and 7.94% (95% CI: 3.67%, 12.39%) higher FVIII levels, after adjustment for demographics (Table 3). There was no relationship between African ancestry and D-dimer or PAP levels among Hispanics. Further adjustment for behaviors and physiologic characteristics did not appreciably change our estimates. Cubic spline model results of the demographic-adjusted relationship between African ancestry and levels of fibrinogen and FVIII among Hispanics are shown in Fig. 2.

Table 3.   Percent difference in hemostatic factor levels per 1 standard deviation*† greater African ancestry and European ancestry among 712 self-identified Hispanic Americans: Multi-Ethnic Study of Atherosclerosis Candidate Gene Study 2000–2002
 % Difference (95% CI)P-value
  1. *1 standard deviation African ancestry = 18.9%; 1 standard deviation European ancestry = 21.9%. Adjusted for age, gender, education, income and field site.

African ancestry
 Fibrinogen2.73 (0.68, 4.82)0.009
 Factor VIII7.94 (3.67, 12.39)0.0002
 D-dimer−0.29 (−8.53, 8.69)0.95
 PAP3.46 (−0.23, 7.29)0.07
European ancestry  
 Fibrinogen1.16 (−0.53, 2.88)0.18
 Factor VIII1.93 (−1.47, 5.44)0.27
 D-dimer−5.38 (−11.97, 1.71)0.13
 Plasmin–antiplasmin2.33 (−0.72, 5.46)0.14
image

Figure 2.  Association of African ancestry with geometric mean fibrinogen (panel A) and factor VIII levels (panel B) among 701 self-identified Hispanic Americans*: MESA 2000–2002. *Adjusted for age, gender, education, income and field site.

Download figure to PowerPoint

There was minimal evidence of a relationship between European ancestry and hemostatic factor levels in Hispanics. The only statistically significant association we observed was that each SD (22%) greater European ancestry was associated with 4.53% (95% CI: 0.74%, 8.47%) higher FVIII levels in the fully-adjusted model (adjusted for demographics, behaviors and physiologic characteristics).

There was no evidence to suggest that relationships between genetic admixture and hemostatic factor levels were modified by sex, educational attainment or income in either self-identified African Americans or Hispanics.

Discussion

  1. Top of page
  2. Abstract
  3. Introduction
  4. Methods
  5. Results
  6. Discussion
  7. Acknowledgements
  8. Disclosure of Conflict of Interests
  9. References
  10. Supporting Information

In this sample of MESA participants self-identified as African Americans and Hispanic Americans, we found modest evidence that genetic admixture is associated with hemostatic factor levels. Among African Americans, greater African ancestry was associated with higher levels of fibrinogen and PAP, but not with higher levels of FVIII and D-Dimer. In Hispanics, greater African ancestry was associated with higher levels of fibrinogen and FVIII, but not D-Dimer and PAP. In spite of some inconsistencies, the present results suggest that genetic differences in allele frequencies or variants contribute to racial/ethnic differences in hemostatic factor levels. Family studies previously established that hemostatic factor levels are heritable [29–31]. However, the finding that ancestry is itself a predictor of hemostatic factor levels provides a more global picture of the role of ancestry-related genetic differences underlying racial/ethnic categories in explaining racial/ethnic differences in hemostatic factor levels.

The absolute magnitudes of the associations of ancestry with hemostatic factor levels were not large; the greatest percent difference of any hemostatic factor per SD ancestry was 7.9%. However, this is to be expected as the magnitudes of racial/ethnic differences in hemostatic factor levels also tend to be relatively modest when race/ethnicity is self-reported. In the MESA population, levels of these hemostatic factors were 5.7% to 18.8% higher among self-identified African Americans than Caucasians. Furthermore, it is well established that within-population differences among individuals account for the vast majority of genetic variation, with differences between major ancestral groups only accounting for 3–5% of variation [32]. In spite of this, Figs 1 and 2 demonstrate that the association between ancestry and hemostatic factor levels is of a magnitude which translates to disease rates. For instance, among Africans Americans, fibrinogen levels were over 20 mg dL–1 higher among African Americans with almost exclusively African ancestry relative to those with greater admixture. A 20 mg dL–1 higher fibrinogen level (about equal to 1 SD higher) is associated with an approximately 19% greater risk of coronary heart disease [33].

There is limited literature on genetic admixture and hemostatic factor levels with which to compare our results. Among self-reported African American participants of the Cardiovascular Health Study (CHS), each SD greater European ancestry was associated with approximately 10% lower D-dimer levels [34]. We did not observe a relation between admixture and D-dimer in the MESA population; however, MESA differs from CHS in that CHS participants were older and had a greater prevalence of coronary heart disease. D-dimer is also unique relative to the other markers we studied in that it is reflective of fibrinolysis as well as thrombosis. It is possible that genetic admixture may be more strongly related to thrombotic than fibrinolytic activity. Consistent with our findings, in a Brazilian study of a racially mixed sample of 125 males, greater Caucasian admixture, as defined by skin pigmentation, was associated with lower levels of FVIII [35].

Several studies have documented that self-reported race/ethnicity is associated with hemostatic factors levels [3–12], but uncertainty exists in that the associations may have been confounded by other factors that correlate with race/ethnicity, in spite of statistical adjustment. Self-reported race/ethnicity is a broad, discrete categorization which often encompasses characteristics such as geographic location of ancestry, cultural tradition, common history and religion, and sometimes a shared genetic heritage [36]. Ancestry refers to a continuous objective measure of genetic similarities and/or differences between and among populations [37]. Given that ancestry is an objective measure based on genetics, it is less likely to be confounded by behaviors and physiologic characteristics than is self-reported race/ethnicity.

Strengths of the present study include evaluation of both African Americans and Hispanic Americans, good pseudoancestral data from African, European and Native American samples which helps to prevent biased estimates in ancestry [38], and MESA’s standardized and extensive data collection protocols, which made it possible to adjust for potential confounders of the relationship between ancestry and hemostatic factor levels. Several limitations of our study should also be noted. First, though self-reported racial/ethnic variation in hemostatic factor levels have been consistently reported [3–12], the magnitudes of these associations have often been small, and our power may have been limited to detect weak effects, especially as we were only evaluating the proportion of racial/ethnic variation owing to genetics. This may have been particularly true for D-Dimer, which had the greatest relative variability among the biomarkers explored. The proportions of ancestry in MESA may also differ from the general population as highly admixed individuals may be less likely to participate in a study such as MESA, which explicitly recruited individuals who self-identified as being African American, Hispanic American, Chinese or Caucasian. An additional limitation is that individuals who self-identify as Hispanic are very heterogeneous [39], and we lacked statistical power to stratify by Hispanic subgroups. Other drawbacks of the present study are that hemostatic factor levels were measured only once, and that even although we attempted to account for confounders, it is possible that residual or unknown confounders may have influenced our results.

To conclude, in this sample of African Americans and Hispanic Americans we found evidence that greater African ancestry was associated with higher levels of several hemostatic factors. Notably, the association for fibrinogen was observed in both groups, although relations between ancestry and other hemostatic factors were less consistent. These results suggest that genetic variation may contribute to variation in hemostatic factor levels by self-reported race/ethnicity. Furthermore, these results indicate that hemostatic factors may be reasonable traits to be explored in admixture mapping. Admixture mapping is a technique which capitalizes on differences in local ancestry to identify novel genetic variants which may be related to phenotypes [40,41], such as hemostatic factor levels.

Acknowledgements

  1. Top of page
  2. Abstract
  3. Introduction
  4. Methods
  5. Results
  6. Discussion
  7. Acknowledgements
  8. Disclosure of Conflict of Interests
  9. References
  10. Supporting Information

This research was supported by contracts N01-HC-95159 through N01-HC-95169 from the National Heart, Lung, and Blood Institute. The authors thank the other investigators, the staff and the participants of the MESA study for their valuable contributions. A full list of participating MESA investigators and institutions can be found at http://www.mesa-nhlbi.org.

Disclosure of Conflict of Interests

  1. Top of page
  2. Abstract
  3. Introduction
  4. Methods
  5. Results
  6. Discussion
  7. Acknowledgements
  8. Disclosure of Conflict of Interests
  9. References
  10. Supporting Information

The authors state that they have no conflict of interest.

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  2. Abstract
  3. Introduction
  4. Methods
  5. Results
  6. Discussion
  7. Acknowledgements
  8. Disclosure of Conflict of Interests
  9. References
  10. Supporting Information
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Supporting Information

  1. Top of page
  2. Abstract
  3. Introduction
  4. Methods
  5. Results
  6. Discussion
  7. Acknowledgements
  8. Disclosure of Conflict of Interests
  9. References
  10. Supporting Information

Table S1. Detectable percent difference per SD* of African ancestry at 80% power, and alpha of 0.05.

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JTH_4663_sm_TableS1.doc40KSupporting info item

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