African Ancestry is a Risk Factor for Asthma and High Total IgE Levels in African Admixed Populations.
ABSTRACT Characterization of genetic admixture of populations in the Americas and the Caribbean is of interest for anthropological, epidemiological, and historical reasons. Asthma has a higher prevalence and is more severe in populations with a high African component. Association of African ancestry with asthma has been demonstrated. We estimated admixture proportions of samples from six trihybrid populations of African descent and determined the relationship between African ancestry and asthma and total serum IgE levels (tIgE). We genotyped 237 ancestry informative markers in asthmatics and nonasthmatic controls from Barbados (190/277), Jamaica (177/529), Brazil (40/220), Colombia (508/625), African Americans from New York (207/171), and African Americans from Baltimore/Washington, D.C. (625/757). We estimated individual ancestries and evaluated genetic stratification using Structure and principal component analysis. Association of African ancestry and asthma and tIgE was evaluated by regression analysis. Mean ± SD African ancestry ranged from 0.76 ± 0.10 among Barbadians to 0.33 ± 0.13 in Colombians. The European component varied from 0.14 ± 0.05 among Jamaicans and Barbadians to 0.26 ± 0.08 among Colombians. African ancestry was associated with risk for asthma in Colombians (odds ratio (OR) = 4.5, P = 0.001) Brazilians (OR = 136.5, P = 0.003), and African Americans of New York (OR: 4.7; P = 0.040). African ancestry was also associated with higher tIgE levels among Colombians (β = 1.3, P = 0.04), Barbadians (β = 3.8, P = 0.03), and Brazilians (β = 1.6, P = 0.03). Our findings indicate that African ancestry can account for, at least in part, the association between asthma and its associated trait, tIgE levels.
- SourceAvailable from: Gabriel De Jesus Bedoya[Show abstract] [Hide abstract]
ABSTRACT: The wide variation in severity displayed during Dengue Virus (DENV) infection may be influenced by host susceptibility. In several epidemiological approaches, differences in disease outcomes have been found between some ethnic groups, suggesting that human genetic background has an important role in disease severity. In the Caribbean, It has been reported that populations of African descent present considerable less frequency of severe forms compared with Mestizo and White self-reported groups. Admixed populations offer advantages for genetic epidemiology studies due to variation and distribution of alleles, such as those involved in disease susceptibility, as well to provide explanations of individual variability in clinical outcomes. The current study analysed three Colombian populations, which like most of Latin American populations, are made up of the product of complex admixture processes between European, Native American and African ancestors; having as a main goal to assess the effect of genetic ancestry, estimated with 30 Ancestry Informative Markers (AIMs), on DENV infection severity. We found that African Ancestry has a protective effect against severe outcomes under several systems of clinical classification: Severe Dengue (OR: 0.963 for every 1% increase in African Ancestry, 95% confidence interval (0.934 - 0.993), p-value: 0.016), Dengue Haemorrhagic Fever (OR: 0.969, 95% CI (0.947 - 0.991), p-value: 0.006), and occurrence of haemorrhages (OR: 0.971, 95% CI (0.952 - 0.989), p-value: 0.002). Conversely, decrease from 100% to 0% African ancestry significantly increases the chance of severe outcomes: OR is 44-fold for Severe Dengue, 24-fold for Dengue Haemorrhagic Fever, and 20-fold for occurrence of haemorrhages. Furthermore, several warning signs also showed statistically significant association given more evidences in specific stages of DENV infection. These results provide consistent evidence in order to infer statistical models providing a framework for future genetic epidemiology and clinical studies.Infection Genetics and Evolution 10/2014; · 3.26 Impact Factor
- [Show abstract] [Hide abstract]
ABSTRACT: There are few birth cohort studies analyzing IgE sensitization in the tropics. We aimed to describe the evolution of total IgE and specific IgE responses to house-dust mite (HDM) allergens and Ascaris in a birth cohort (Risk Factors for Asthma and Allergy in the Tropics, FRAAT), analyzing their relationships with wheezing. Total and specific IgE were measured by ImmunoCap in mothers and children at four different time points (S1-S4) between 0 and 42 months. Parasite infection was evaluated by stool examination. Maternal total IgE (aOR: 2.43, 95% CI: 1.09-5.43; p = 0.03) and socio-demographic factors were associated with high cord blood (CB) total IgE. High CB total IgE was positively associated with higher Blomia tropicalis and Ascaris-specific IgE values during lifetime, but protected from recurrent wheezing (aOR: 0.26, 95% CI: 0.08-0.88, p = 0.03). Prevalence rates of IgE sensitization were high; at around 3 yr old, they were 33.3, 18.6, and 26.5% for B. tropicalis, Dermatophagoides pteronyssinus, and Ascaris, respectively. Indicators of unhygienic conditions were risk factors for HDM and Ascaris sensitization in children. A weak statistical association between B. tropicalis-specific IgE and ever wheezing was found (aOR: 1.47 95% CI: 1.00-2.28, p = 0.05). In a socioeconomically deprived community from the tropics, sensitization to HDM allergens was very frequent at early life, especially to B. tropicalis. In contrast to expected according to the hygiene hypothesis, unhygienic/poverty conditions were risk factors for allergen sensitization. High CB total IgE levels were a risk factor for allergen sensitization but protected from recurrent wheezing.Pediatric Allergy and Immunology 12/2013; · 3.38 Impact Factor
African Ancestry is a Risk Factor for Asthma and High
Total IgE Levels in African Admixed Populations
Candelaria Vergara,1Tanda Murray,2Nicholas Rafaels,1Rachel Lewis,1Monica Campbell,1Cassandra Foster,1Li Gao,1
Mezbah Faruque,3Ricardo Riccio Oliveira,4Edgar Carvalho,4Maria Ilma Araujo,4Alvaro A. Cruz,5Harold Watson,6
Dilia Mercado,7Jennifer Knight-Madden,8Ingo Ruczinski,9Georgia Dunston,3Jean Ford,2Luis Caraballo,7Terri H. Beaty,2
Rasika A. Mathias,1and Kathleen C. Barnes1∗
1Division of Allergy and Clinical Immunology, Department of Medicine, Johns Hopkins University (JHU), Baltimore, Maryland;2Department of
Epidemiology, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, Maryland;3National Genome Center at Howard
University, Washington, DC;4Servico de Imunologia, Hospital Universitario Professor Edgard Santos, Salvador, Bahia, Brazil;5ProAR – Nucleo de
Excelencia em Asma, Federal University of Bahia and CNPq, Salvador, Bahia, Brazil;6Faculty of Medicine, University of the West Indies, Cave Hill
Campus, Barbados;7Institute for Immunological Research, University of Cartagena, Cartagena, Colombia;8Tropical Medicine Research Institute,
The University of the West Indies, Jamaica, West Indies;9Biostatistics, Bloomberg School of Public Health, Johns Hopkins University, Baltimore,
Received 13 June 2012; Revised 21 November 2012; accepted revised manuscript 22 November 2012.
Published online 2 April 2013 in Wiley Online Library (wileyonlinelibrary.com). DOI 10.1002/gepi.21702
anthropological, epidemiological, and historical reasons. Asthma has a higher prevalence and is more severe in populations
with a high African component. Association of African ancestry with asthma has been demonstrated. We estimated admixture
proportions of samples from six trihybrid populations of African descent and determined the relationship between African
ancestry and asthma and total serum IgE levels (tIgE). We genotyped 237 ancestry informative markers in asthmatics
and nonasthmatic controls from Barbados (190/277), Jamaica (177/529), Brazil (40/220), Colombia (508/625), African
Americans from New York (207/171), and African Americans from Baltimore/Washington, D.C. (625/757). We estimated
individual ancestries and evaluated genetic stratification using Structure and principal component analysis. Association of
African ancestry and asthma and tIgE was evaluated by regression analysis. Mean ± SD African ancestry ranged from
0.76 ± 0.10 among Barbadians to 0.33 ± 0.13 in Colombians. The European component varied from 0.14 ± 0.05 among
Jamaicans and Barbadians to 0.26 ± 0.08 among Colombians. African ancestry was associated with risk for asthma in
Colombians (odds ratio (OR) = 4.5, P = 0.001) Brazilians (OR = 136.5, P = 0.003), and African Americans of New York
(OR: 4.7; P = 0.040). African ancestry was also associated with higher tIgE levels among Colombians (β = 1.3, P = 0.04),
Barbadians (β = 3.8, P = 0.03), and Brazilians (β = 1.6, P = 0.03). Our findings indicate that African ancestry can account
for, at least in part, the association between asthma and its associated trait, tIgE levels.
Genet Epidemiol 37:393–401, 2013.C ?2013 Wiley Periodicals, Inc.
KEY WORDS: African; asthma; ancestry
Characterization of genetic admixture of populations in the Americas and the Caribbean is of interest for
Race and ethnicity are complex constructs incorporating
social, cultural, and genetic factors. Populations that mi-
were dispersed across the Americas, and their contemporary
Contract grant sponsor: National Institutes of Health; Contract grant number:
Contract grant sponsor: University Hospital of West Indies. Contract grant sponsor:
grant sponsor: Mary Beryl Patch Turnbull Scholar Program. Contract grant sponsor:
Brazilian National Research Council (CNPq).
∗Correspondence to: Kathleen C. Barnes, 5501 Hopkins Bayview Circle, Baltimore,
MD 21224. E-mail: email@example.com
ancestors have varying proportions of African admixture de-
pending upon local demographic history and patterns of ad-
mixture, geographical location, and other factors [Via et al.,
2011; Wang et al., 2008]. Determination of the ancestral ori-
epidemiological, and historical interest and affords opportu-
nities to study the evolutionary biology of the ancestral as
well as the admixed populations.
Differences in African or other ancestry proportions be-
tween cases and controls is a confounding factor in ge-
netic association studies of admixed populations because
differences in admixture proportions among subgroups
can erroneously suggest association with disease instead of
ancestry at loci where allele frequencies differ between the
ancestral populations (e.g., population stratification) [Car-
don and Palmer, 2003; Spielman et al., 1993; Ziv and
Burchard, 2003]. This situation is typically addressed by
C ?2013 WILEY PERIODICALS, INC.
genotyping ancestry informative markers (AIMs) to esti-
mate the individual ancestral proportions for major putative
parental populations in admixed groups, and even though
admixture or eigenvalues derived from principal component
analysis (PCA) in the model used to evaluate genetic associ-
ations [McKeigue, 2007; Patterson et al., 2006; Pritchard and
Alternatively, admixed populations provide a unique op-
different prevalences or degrees of severity among specific
the prevalence, morbidity, and mortality of allergic airway
diseases, such as asthma, is disproportionately high among
et al., 2005, 2011; El-Ekiaby et al., 2006; Gold et al., 1993;
Lang et al., 2009; Lester et al., 2001; Moorman et al., 2007;
in African countries and countries with African admixture
(i.e., Latin America) [Pearce et al., 2007]. The Global Strat-
egy for Asthma Management and Prevention report suggests
that African ancestry itself is a risk factor [GINA, 2008]. The
usual source of airway inflammation in asthma is an im-
munoglobulin E (IgE)-mediated reaction initiated by expo-
ated with serum total IgE (tIgE) levels [Burrows et al., 1989;
Marsh et al., 1974]. Higher serum tIgE levels have also been
observed among African Americans with persistent asthma
compared to whites and other ethnic groups [Grant et al.,
2000; Grundbacher and Massie, 1985]. The differences are
noticeable even early in life as described in a children cohort
selected from a multiethnic society, where black newborns
had significantly higher concentrations of cord blood serum
shown to have significantly higher frequencies in individuals
[Barnes et al., 2007; Caggana et al., 1999; Green et al., 1998;
Maxwell et al., 2005; Ness et al., 2004]. Also, a significant
ancestry association peak on chromosome 6q14 (rs1361549)
was associated with asthma exclusively in African American
subjects with local European admixture [Torgerson et al.].
Previously, we observed an association between a well-
et al., 2008]. Analyzing 44 AIMs, Choudhry and colleagues
risk for asthma among Puerto Ricans with higher socioeco-
nomic status compared to those with lower socioeconomic
status [Choudhry et al., 2006]. Kumar et al. demonstrated
that African ancestry was inversely related to forced expira-
participants self-identified as African American in the Coro-
Genetic Epidemiology, Vol. 37, No. 4, 393–401, 2013
nary Artery Risk Development in Young Adults (CARDIA)
study, the Health, Aging, and Body Composition (HABC)
study, and the Cardiovascular Health Study (CHS) [Kumar
et al., 2010], and in a recent publication, African ancestry
we estimated individual African ancestry using a panel of
52 AIMs in asthmatics and nonasthmatics from Cartagena
(Colombia, South America), and determined that African
high tIgE levels [Vergara et al., 2009]. Taking in account the
relevance of replicating genetic associations [Chanock et al.,
of theassociation accordingto thedegreeof Africanancestry
markers, and extended these studies to include additional,
independent African Caribbean and African American pop-
ulations from Colombia, Barbados, Jamaica, Brazil, and the
lationship between African ancestry and asthma and serum
We included 467 Barbadian nonrelated individuals (190
cases and 277 nonasthmatic controls) from a study on the
genetics of asthma as previously described [Barnes et al.,
1996; Mathias et al., 2010] and in supplementary material
A sample of 706 unrelated individuals (177 asthmatics,
529 nonasthmatic controls) was recruited from Kingston, St.
Andrew, and St. Catherine, Jamaica as part of the Jamaican
terials and methods and in references [Ashley et al., 1988;
Tulloch-Reid et al., 2010]. All subjects provided informed
written consent to participate as approved by the University
of the West Indies, Mona campus.
Asthmatic (N = 40) and nonasthmatic (N = 220) nonre-
Camarao, Genipapo, Sempre Viva, and Cobo) in the district
of Conde, Bahia, located in the North East Coast of Brazil
as described in detail elsewhere [Grant et al., 2011; Vergara
et al., 2008] and in Supporting Information material and
methods. Written consent was obtained from adult individ-
uals or parent or guardian of children as approved by the
Johns Hopkins Bayview Medical Center and Universidade de
Federal de Bahia IRBs.
A sample of 1,133 unrelated individuals (508 asthmatics
and 625 nonasthmatic controls) were recruited from the
Caribbean coastal city of Cartagena as described in detail
elsewhere [Vergara et al., 2008, 2009] and in Supporting
Information materials and methods. All subjects or their
guardian/responsible adult gave written consent for their in-
clusion in the present study as approved by the Bioethics
Committee of the School of Medicine of The University of
Two samples of self-reported African Americans were in-
A group of 1,382 individuals (625 asthma cases and 757 un-
related, unaffected controls) ascertained participating in Ge-
nomic Research on Asthma in the African Diaspora (GRAAD)
recruited in the Baltimore-Washington D.C. metropolitan
area and participants in the Baltimore Asthma Severity Study
matic controls) were recruited in New York and participated
study. Details of these samples are described elsewhere [Ford
et al., 2001; Mathias et al., 2007; Murray et al., 2010; Pesola
et al., 2004] and in Supporting Information material and
methods. The study protocols, recruitment procedures, and
consent forms were approved by the Institutional Review
Board of Columbia University, Johns Hopkins University,
and Howard University.
Sera were available in the Barbadian, Jamaican, Brazilian,
Colombian, and African American samples from Baltimore-
For all datasets, tIgE values were log-transformed to reduce
the skewness of the distribution. Measurements were not
available for African Americans from New York and for par-
ticipants of the BASS study.
Selection of AIMs and genotyping
We selected 237 AIMs distributed across 22 autosomes as
presented in Supporting Information Table SI. The mark-
ers were a subset of 416 AIMs previously selected [Murray
et al., 2010] from the 650Y panel based on a published list
of AIMs [Cheng et al., 2009] showing large allelic frequency
difference (δ) among the three putative parental populations
(European, African, and Asians) using HapMap Phase 2 ref-
erence populations (CEU, YRI, CHB), respectively.
Due to limitations in the availability of Native Ameri-
cans DNA samples, for this analysis, we used Asians as a
proxy for Native Americans because they are closely related
downloaded from HapMart (http://hapmart.hapmap.org/
BioMart/martview), an extension of the HapMap data re-
source. A marker was considered informative if 0.30 differ-
ence of the allelic frequencies existed between any of two
parental groups. Blood samples were collected from all sub-
jects and genomic DNA was extracted using standard pro-
tocols. Samples were genotyped according to the manufac-
turer’s protocol at the Center for Inherited Disease Research
on an Illumina BeadStation 500G Golden Gate genotyping
platform using a custom panel (GS0011473-OPA). Geno-
typing plates were balanced by gender and asthma status
and HapMap DNA samples and duplicates were included as
Comparisons of the demographic characteristics among
asthmatics and nonasthmatics were performed by means of
Student’s t-test and χ2test as needed using STATA software
(StataCorp. 2009. Stata Statistical Software: Release 11. Col-
lege Station, TX: StataCorp LP.). Arlequin version 3.11 soft-
ware [Excoffier et al., 2005] was used to calculate allele and
genotype frequency of the AIMs, departure of genotype fre-
quencies from Hardy-Weinberg equilibrium (HWE), link-
age disequilibrium between each pair of markers (as an in-
dicator of stratification) independently for each sample set
and genetic differentiation among the analyzed populations
using FSTgenetic distances [Reynolds et al., 1983; Slatkin,
1995]. Average population admixture and individual admix-
ture estimates for each sample set were determined using
a model-based clustering method by grouping data for the
total sample in three ancestral populations (K = 3) to re-
flect the admixture history in the Caribbean and North and
South America with the software Structure (version 2.3.3,
http://pritch.bsd.uchicago.edu/software) and assessment of
gram from the software package eigenstrat [Patterson et al.,
2006] including the three putative ancestral populations as
reference. We investigated the relationship between disease
status and African ancestry by logistic regression analysis us-
cestry as independent variable, while adjusting for potential
confounders (age, sex). To determine associations of African
ancestry with tIgE levels, a linear regression model was used
needed, Glmperm and lmperm packages in R were used to
perform permutation analysis to confirm the association re-
African ancestry and tIgE levels, meta-analysis P-values were
Genetic Epidemiology, Vol. 37, No. 4, 393–401, 2013
computed using Stouffer’s Z-score method [Stouffer et al.,
nonasthmatics in each sample are presented in Table I. Mean
described previously [Grant et al., 2008; Vergara et al., 2009,
2008], wherein Brazilians showed higher tIgE levels than the
of extracellular parasitic disease in this population [de Jesus
et al., 1993]. tIgE was significantly higher in asthmatics com-
pared to nonasthmatics in all samples sets (P≤0.001) except
Brazilians (P = 0.64). Results about allelic frequencies, HWE,
are presented in Table II and individual admixture estimates
are presented in Figure 1. The distribution of the African an-
cestry proportions are displayed as box plots in Supporting
try was highest in West Indians (Jamaicans, 0.76±0.10; Bar-
badians, 0.76±0.10) and African Americans from New York
(0.70 ± 0.15) and Baltimore-Washington D.C. (0.69 ±0.12)
and lowest in the two South American samples (Brazilians,
0.45 ± 0.12; Colombians, 0.33 ± 0.13). The average Euro-
pean component ranged from a low of 0.14 ± 0.005 among
Jamaicans and Barbadians to a high of 0.26 ± 0.08 among
Colombians. The average Asian ancestry ranged from 0.08±
0.06 among Barbadians to 0.40 ± 0.13 among Colombians.
component and the estimates of individual African ancestry
in each of the samples (Spearman’s ρ > 0.98, P < 0.0001 for
each pair of comparisons).
Association of African Ancestry and Asthma and tIgE
Table III summarizes results of regression analyses of
African ancestry and asthma and tIgE. African ancestry was
associated with a significant risk for asthma among several
populations. The odds ratio (OR) for asthma is associated
with a unit increase in African admixture proportion (from
0 to 1). It was significant for Colombians (OR: 4.5; 95% CI:
1.79–11.27; P = 0.001), Brazilians (OR: 136.5; 95% CI: 5.4–
3405.6; P = 0.003), and African Americans of New York (OR:
4.7; 95% CI: 1.07–21.0; P = 0.04). In Brazilians, permutation
Table I. Descriptive characteristics of six African ancestry populations
Male gender Age Total IgE†
PopulationsN (%)N (%) P value Mean (SE)P value Geom. mean (95%CI)P value
African American (New York†) Asthmatics
*NA: Not available;†Plus-minus values are means±SE. Log-transformed total IgE concentrations measured in ng/ml.†REACH, Reducing Emergency Asthma Care in Harlem.
‡BASS, Baltimore Asthma Severity Study; GRAAD, Genomic Research on Asthma in the African Diaspora.
Table II. African, European and Asian ancestry proportions for Barbadians, Jamaicans, Brazilians, Colombians and African Americans
Ancestry proportions (Mean, SD)
Controls PopulationTotal AsthmaticsTotal AsthmaticsTotal Asthmatics
African Americans (New York)
Genetic Epidemiology, Vol. 37, No. 4, 393–401, 2013
populations available in HapMap (CEU, CHB, and YRI).
Table III. Results of regression analyses of African ancestry
proportions and asthma and tIgE levels for Barbadians,
Jamaicans, Brazilians, Colombians and two African American
Asthma Total serum IgE levels
(β, 95% CI, P value)**
Population (OR, 95% CI, P value)*
African Americans (New York)
*Adjusted by age and sex; **Adjusted by age, sex and asthma status. #NA = Not
available. The odds ratio (OR) for asthma is associated with a unit increase in African
admixture proportion (from 0 to 1).
ponent plots for each sample of each population are shown
in Supporting Information Figure S2. The plotted individ-
uals are discriminated by affection status. For the Jamaican
and the two African American populations, cases and con-
in the distribution of the first principal component among
York, a significant difference was found when comparing the
distribution of the first principal component among cases
and nonasthmatic controls (P<0.001).
Of the five samples with tIgE data available, African an-
cestry was associated with tIgE levels in Colombians (β: 1.3;
95% CI: 1.01–1.7; P = 0.04), Barbadians (β: 3.8; 95% CI:
1.1–13.1; P = 0.030), and Brazilians (β: 1.6; 95% CI: 1.1–2.6;
P = 0.03; Permutation P = 0.05). No relationship between
African ancestry and asthma or tIgE was detected among the
Jamaicans or African American of Baltimore-Washington,
D.C. No relationship between ancestry and asthma or tIgE
was detected among the Jamaicans or African American of
Baltimore-Washington, D.C. No associations were observed
the datasets. Supporting Information Figure S4 graphically
ancestry and tIgE levels in each one of the analyzed popu-
lation and the P-value calculated for all populations. The
P-value of the meta-analysis of the five analyzed populations
was statistically significant (P = 0.019).
In this study, we determined the admixture propor-
tion of six samples from populations of African descent
Genetic Epidemiology, Vol. 37, No. 4, 393–401, 2013
representing geographical regions across Continental Amer-
ica and two islands in the Caribbean, for which the African
Diaspora figured prominently in the demographic history
of these populations. We also investigated the association
of African ancestry and asthma and tIgE levels including a
sample of considerable size for each population and a com-
prehensive panel of AIMs distributed across the genome.
We included only self-reported unrelated individuals in
each of the analyzed populations to minimize the potential
effect of relatedness in calculations of allelic frequencies of
the AIMs and consequently in the ancestry estimates and as-
sociation analysis. Also, African Americans from Baltimore-
a Genome Wide Association Study (GWAS) panel of and all
from the dataset prior to this analysis [Mathias et al., 2010].
it would have a significant effect on our association analysis.
We observed a wide range of average proportions of parental
populations across the samples and a significant association
of African ancestry and asthma and serum tIgE levels. To
date, measured by number of populations included, sample
size per populations, and number of AIMs, this is one of the
largest studies to analyze ancestry proportions and the rela-
and the Caribbean.
Although each one of the analyzed populations has a
unique history, they share certain characteristics regarding
to the dynamics of the admixture process. Historical records
West Africans, Europeans, and Native Americans. The pro-
cess of admixture extended across Latin America and the
Caribbean during the 15th through 19th centuries, includ-
ing the arrival of Europeans (predominantly Spanish, Por-
tuguese, and British) and the extinction of Native Americans
converging with the arrival and expansion of African slaves,
largely from West Africa during the 16th and 19th centuries.
Nevertheless, the analyzed populations underwent diverse
patterns of admixture given the location of settlement of the
parental populations approximately 500 years ago [Curtin,
1969; Salzano, 2002; Sanchez-Albornoz, 1974; Thomas
cluded in the current study, ancestry estimates vary by re-
eral factors contributed to make up the current genetic pool
including admixture, genetic drift, migration, and recent ge-
netic flow [Winkler et al., 2010]. Asian ancestry estimates,
which are a surrogate for Native American ancestry are the
lowest of the three parental components in Barbadians, Ja-
maicans, and African Americans. Asian ancestry estimates
obtained with this set of AIMs showed a large variation, and,
we conclude these estimates may well be erroneous rather
than indicative of admixture in contrast to estimates for the
other two parental populations. It is well known that the Na-
Genetic Epidemiology, Vol. 37, No. 4, 393–401, 2013
tive American population was decimated and exterminated
along the whole continent either by disease or labor [De las
was a rapid annihilation of the Arawak population following
colonization of the Spaniards from 1494 to 1655 in Jamaica;
Barbados [Rouse, 1992] and for the Caribs and Taironas in
Cartagena [Meisel and Aguilera, 1997].
We found a predominant proportion of African ancestry
and a low proportion of European ancestry in the popula-
tions of the Caribbean Islands. According to the records, the
tion in Barbados was around 900,000 [Pepin, 2005] and out-
numbered European settlers by a proportion of 20:1 [Simms
et al., 2010]. Europeans were also decimated by disease and
the predominant population that finally contributed to the
contemporary genetic pool was of African origin [Benn-
Torres et al., 2008; Knight, 1997]. A history that is very
similar to that described in the island of Jamaica [Benn-
Torres et al., 2008]. In continental America, a highly diverse
genetic makeup has been noted previously including territo-
ries of Colombia and Brazil (Supporting Information Table
SIII). Local history, diversity of the geography, as well as so-
cial and economic factors may have played a crucial role in
the dynamic of admixture after the first admixture event.
African admixture is especially pronounced in the coastal
states, which underwent a social history similar to the rest
of the Caribbean, whereby African slaves were imported as
(Cartagena, Choco) or located in the route of transportation
of slaves trough the inner country and those regions close
to the original sugar cane plantations [Rojas et al., 2010].
A high variation in admixture proportions has also been
observed in different regions of Brazil among and within
studies, however there has been a pattern observed indicat-
ing higher European ancestry in southern Brazil compared
to the north as well as isolated populations of predominant
African descent that do not follow this pattern [Pena et al.,
2009; Santos et al., 2010]. If we compare our results to pre-
vious ones in the included populations (Supporting Infor-
mation Table SIII), the estimates obtained are slightly differ-
ent to those described before which can be attributable to
the markers chosen, the samples analyzed, and the statistical
methods used in the studies. Nevertheless, we consider that
is accurate. The current estimates are very consistent with
those obtained with a significant higher number of markers
mates obtained for the Colombian population were different
compared with those obtained in the same individuals using
a panel of 52 AIMs [Vergara et al., 2009]. These patterns of
variation in ancestry across countries seem to be a common
feature across the Americas even in small islands as Puerto
association studies in Latin American populations, given the
highprobability ofpopulation stratification,eveninsamples
from a single country or a geographic region, and highlights
genetic association study in these populations.
We observed a pattern correlating the geographic prox-
imity of the samples and the genetic differentiation values
observed with two independent statistical approaches (FST
values and PCAs, Supporting Information Table SII and Fig-
(FST: 0.02, P = 0.001), close to the CEU samples and fur-
ther apart from the West African cluster. In contrast, African
Americans, Barbadians, and Jamaicans clustered very closely
to each other and to the YRI samples, which is consistent
with the low level of genetic differentiation detected by the
FSTstatistic in those groups.
In this study, we found that African ancestry conferred a
significant risk for asthma and higher levels of serum tIgE
incomparison withnon-African ancestries.Theassociations
were not due to potential confounders as gender and age. We
previously observed the association of African ancestry with
in the gene encoding the DARC, a well-known marker of
African ancestry as conferring risk for asthma and tIgE in a
similar group of populations [Vergara et al., 2008]. In sub-
sequent analyses, we investigated a Colombian case/control
database and genotyped a set of 52 AIMs with similar re-
sults (OR for asthma associated with African admixture was
2.97 (95% CI: 1.08–8.08) and for tIgE 1.9 (95% CI: 1.17–
3.12) [Vergara et al., 2009]. In this case, we replicated our
findings with the same direction of the effect for asthma
and tIgE in Brazilians and in Colombians (this time using
a larger dataset and a higher number of AIMs), for asthma
in African Americans from New York, and for tIgE in Bar-
badians. When comparing our results to those described in
other admixed populations, we found that outcomes varied
according to the populations and phenotype analyzed, de-
sign of the studies, and covariates included. Our results are
highly consistent with those recently published for African
Americans of the REACH cohort, where it was determined
an OR of 1.16 (95% CI: 1.06–1.28; P = 0.002) for the risk of
asthma per 10% increase of African ancestry after correcting
by age, gender, and study site [Flores et al., 2012]. Similarly,
in a Puerto Rican population, asthma risk increased with
African ancestry among individuals with higher socioeco-
nomic status [Choudhry et al., 2006] and European ancestry
vere asthma as measured by both FEV1 and by a clinical as-
and the current study, however, that may explain the dis-
crepancy in the results, including the analyzed phenotypes
(FEV1 vs. asthma/IgE) and the ancestries analyzed (Euro-
pean compared to Native American vs. African compared to
even though the phenotype is not identical, our result are
similar to those described by Kumar et al., who determined
that African ancestry was associated with increased odds of
peanut and milk specific IgE levels of≥5 kUA/L in children
Individual genetic ancestries as determined by AIMs have
been also described as an important determinant of vari-
ation of multiple traits and/or susceptibility to other dis-
eases. Among African American, Hispanic American, and
European American children, a greater African admix-
ture proportion has been associated with lower fat mass,
lower total abdominal adipose tissue, lower intraabdominal
adipose tissue, lower subcutaneous abdominal adipose tis-
sue, and higher bone mineral content, after adjusting for
socioeconomic status, sex, age, height, race/ethnicity, and
pubertal status [Cardel et al., 2010]. Percentage of African
ments (FEV1, FVC) in three independent cohorts of African
Americans across a wide range of ages [Kumar et al., 2010].
In our study, we observed no associations between African
ancestry and asthma in the African American group from
lack of association with asthma observed these populations
could be attributed to the low variance of the African ances-
try proportions in these populations (Supporting Informa-
tion Figure S1) and low proportions of European and Asian
ancestries, which in turn underpowered the comparisons.
Among African Americans from the Baltimore-Washington
D.C. metropolitan area, the sample size had power of only
0.25 to detect an OR of 4, given the European ancestry pro-
portions and the case/control relation in those populations
[Gauderman, 2006]. Power was even lower for Jamaicans
and Barbadians, where a considerably larger sample size
(N = 2,757 for Barbados and N = 2,182 for Jamaica) would
be required to adequately evaluate the effect. Environmental
recruiting that potentially determine light differences in the
in those groups.
The replication of our results in several populations with
the same direction of the effect provide evidence that ge-
netic factors contained in the African genetic component
of hybrid populations contribute to ethnic disparities for
asthma, and that studying populations of West African de-
sociated with asthma susceptibility. For example, Choudhry
et al. performed admixture mapping for asthma including
Puerto Rican individuals with moderate-to-severe asthma
and nonasthmatic controls and identified chromosomal re-
gions 5q23.3 and 13q13.3 as potential regions harboring
genes for asthma in this population [Choudhry et al., 2008].
Differences in association in candidate genes for asthma ac-
cording to ancestry have also been identified, indicating that
specific and maybe different genetic risk factors account for
asthma susceptibility in African descent populations com-
pared with European descent populations [Barnes et al.,
2007; Baye et al.]. We are aware of several caveats in our
study design, one of which is the use of Asian populations
as representative of Native American populations. Another
Genetic Epidemiology, Vol. 37, No. 4, 393–401, 2013
limitation is the lack of adjustment by socioeconomic status,
a potentially critical confounder. Even though the Colom-
bian samples used in this study were selected using the same
approach as a previous report, in which the association of
African ancestry and asthma remained after correcting for
socioeconomic status [Vergara et al., 2009], we did not have
access to the same level of socioeconomic status in the other
populations in this study, and were therefore unable to eval-
uate the effect of this potential confounder. In summary,
among populations of African descent distributed in differ-
be efficiently corrected with this comprehensive set of mark-
ers in any future association studies. These populations are
an excellent tool to examine loci associated with asthma and
tIgE by admixture mapping.
We thank all the individuals participating in this study. We thank Jane
Romm, Roxann Ashworth, Alan Scott, Kim Doheny, Jie Zhang and Corinne
Boehm, members of the Center for Inherited Disease Research for the valu-
preparation of the samples. We also thank Patricia Oldewurtel for technical
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