Working… Menu

Genetic Epidemiology of Asthma in Costa Rica

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00021840
Recruitment Status : Completed
First Posted : August 7, 2001
Last Update Posted : August 4, 2014
National Heart, Lung, and Blood Institute (NHLBI)
Information provided by (Responsible Party):
Scott T. Weiss, Brigham and Women's Hospital

Brief Summary:
To identify genetic factors that influence the development of asthma in Hispanics.

Condition or disease
Asthma Lung Diseases

Detailed Description:


Asthma is a major public health problem in the United States, with particularly high prevalence rates among some Hispanic groups. Genetic linkage studies of this disease are of potentially great utility for the identification of those at risk, the search for new pharmaceutical treatments, and designing interventions to prevent development of asthma. Study power is greatly enhanced if a relatively isolated, homogeneous population with a significant prevalence of asthma can be identified. Such a population does not exist among Hispanics in the United States but is available in the Central Valley of Costa Rica.


The study concentrates on a genetically isolated Hispanic population with high asthma prevalence living in the Central Valley of Costa Rica. A genome screen will be conducted on large pedigrees multiplex for asthma and linkage analysis performed for seven intermediate phenotypes related to asthma including airway responsiveness; FEV1; bronchodilator responsiveness; skin test reactivity to common aeroallergens; serum total and allergen-specific IgE; and peripheral blood eosinophil count. A genome screen will also be conducted in the parent-child trios, and ancestral haplotypes will be reconstructed to identify regions influencing asthma-associated phenotypes. Within candidate regions demonstrating both linkage in extended pedigrees to asthma and/or asthma-related phenotypes and significant linkage disequilibrium within the unrelated asthmatic subjects, fine mapping will be performed by testing for genetic association to single nucleotide polymorphisms within positional candidate genes.

Layout table for study information
Study Type : Observational
Actual Enrollment : 4245 participants
Observational Model: Family-Based
Time Perspective: Cross-Sectional
Official Title: Genetic Epidemiology of Asthma in Costa Rica
Study Start Date : July 2001
Actual Primary Completion Date : July 2011
Actual Study Completion Date : July 2011

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Asthma

Homogen Hispanic pop/Cent Valley CRA
Homogeneous Hispanic population from the Central Valley of Costa Rica

Primary Outcome Measures :
  1. Asthma diagnosis and asthma morbidity [ Time Frame: Baseline/entry to study ]

Secondary Outcome Measures :
  1. Lung function measures [ Time Frame: 11 years ]
    Includes lung function measures via spirometry, pre-/post-bronchodilator (BD) results, methacholine challenge results, specific IgE measurements, exposure measurements (e.g., house dust samples/allergens, endotoxin levels in house dust, questionnaire-based exposures to smoking, pets, siblings, etc.)

Biospecimen Retention:   Samples With DNA
Blood (and its components, e.g., serum, WBC, etc.)

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

Layout table for eligibility information
Ages Eligible for Study:   6 Years and older   (Child, Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Sampling Method:   Probability Sample
Study Population
Homogeneous Hispanic population from the Central Valley of Costa Rica

Selection and Extension of Family Pedigrees

Probands will be selected on the basis of a physician diagnosis of asthma; a history of recurrent asthma attacks or at least 2 respiratory symptoms; and either airway hyperresponsiveness to methacholine or significant response to bronchodilator (Albuterol) administration. At least 15 families, each having at least two siblings and no more than one parent with a physician diagnosis of asthma will be ascertained and enrolled into this study in Costa Rica. All available first- and second-degree relatives of the proband will be enrolled, including affected and unaffected individuals.

Probands will be recruited from 72 asthmatic children ages 6-12 yr that participated in phase II of the International Study of Asthma and Allergies in Childhood (ISAAC). The Principal Investigator for this study in Costa Rica, Dr. Manuel Soto-Quiros, has been collaborating with us for over a year on a pilot study of the genetics of asthma in Costa Rica. Informed consent for this study was approved by the IRB of the Hospital Nacional de Ninos (San Jose, Costa Rica) and the Costa Rican Ministry of Health, and approval was obtained from the Institutional Review Board of the Brigham and Women's Hospital for genotyping and data analysis. The parents of these children provided information on their respiratory health status and that of their children. Lineages for these 72 children (the probands) were traced back at least three generations. All of these children have at least 6 great-grandparents from Central Valley origins, and are therefore descended primarily from the original founders of the population of the Central Valley of Costa Rica. After determining eligibility, Dr. Soto-Quiros will contact the parents of eligible children. If we are unable to recruit 15 such families from the 72 families participating in Phase II of ISAAC, we will apply the same criteria for selection of the family pedigrees to 315 parent-child trios enrolled in the proposed study. We will, however, exclude trios that are selected for pedigree extension from any of the analyses planned on parent-child trios recruited for the present study. Parents of eligible children will be contacted by Dr. Soto-Quiros by mail or by phone, according to their preference. Once an asthmatic child's family is selected for extension, we will give copies of a brief study description to the proband's parents, so that they can keep a copy for themselves and distribute the others to interested relatives. We will then ask the proband's parents to ask their relatives for permission to be contacted regarding the study. Relatives that have given us permission to be contacted through the proband's parents will be called by telephone to explain the study and to set up interviews.

Parent-Child Trios

Probands will be selected using the same criteria outlined above. 1,200 asthmatic children and their parents (3,600 individuals) will be ascertained and enrolled in this study in the Central Valley of Costa Rica. Probands will be recruited from approximately 3,500 schoolchildren ages 6-12 yr from the Central Valley of Costa Rica. A short screening questionnaire will be administered to the parents of these children to obtain information about the child's respiratory health status and the last names of both of his/her parents. The parents will be instructed to have their child take the completed questionnaire back to school in a sealed envelope. Based on this information, we anticipate selecting 800 children with a physician diagnosis of asthma; either >/= 2 respiratory symptoms or history of recurrent asthma attacks; and a high probability of having >/= 6 great-grandparents from Central Valley origins, as determined by our genealogist. Once an asthmatic child's family is selected, we will ask permission of the parents to conduct methacholine challenge testing on the index children to determine whether or not they are true asthmatics.

Inclusion Criteria

A family will be eligible for inclusion in this study only if the asthmatic proband in that family meets all of the following criteria. Each proband must:

  1. Be at least 6 years of age
  2. Have a physician diagnosis of asthma and either >/= 2 respiratory symptoms or a history of recurrent asthma attacks
  3. Have either airway hyperresponsiveness to methacholine (PD20 </= 16 mg/ml) or (if the FEV1 is </= 65% of predicted) a significant bronchodilator response (an increase of at least 12% from baseline FEV1)
  4. Have at least 6 great-grandparents born in the Central Valley of Costa Rica
  5. Have his/her parents give voluntary written consent to participate in the study
  6. Give his/her assent to participate in the study.
  7. Have at least 2 siblings with physician-diagnosed asthma and no more than one parent with a physician diagnosis of asthma

All first- and second-degree relatives of the proband, affected and unaffected will be enrolled in the study of 15 large, multigenerational family pedigrees if available and willing to participate.

The natural mother and father of the proband will be enrolled in the study of 600 parent-child trios if available and willing to participate.

Exclusion Criteria

A subject will not be eligible for inclusion in this study if any of the following criteria apply. Each subject must not:

  1. Be adopted
  2. Have a chronic respiratory disorder other than asthma (e.g., active tuberculosis, bronchiectasis). Inactive tuberculosis is not an exclusion criterion
  3. For the study of large, multigenerational pedigrees only: Have a familial relationship to any of the remaining fourteen (14) families over the last four generations.

Subject reconsideration for Inclusion

Subjects fulfilling the following exclusion criteria below may be eligible for inclusion in the study at a later date provided that the study physician does not feel that their participation will adversely influence the results of the study.

1. Subjects who have taken antibiotics for respiratory disease within one month or have had respiratory infection within 6 weeks of the visit.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00021840

Layout table for location information
Costa Rica
Hospital Nacional de Ninos
San Jose, Costa Rica
Sponsors and Collaborators
Brigham and Women's Hospital
National Heart, Lung, and Blood Institute (NHLBI)
Layout table for investigator information
Principal Investigator: Scott T. Weiss, MD, MS Brigham and Women's Hospital

Publications of Results:
Melén E, Granell R, Kogevinas M, Strachan D, Gonzalez JR, Wjst M, Jarvis D, Ege M, Braun-Fahrländer C, Genuneit J, Horak E, Bouzigon E, Demenais F, Kauffmann F, Siroux V, Michel S, von Berg A, Heinzmann A, Kabesch M, Probst-Hensch NM, Curjuric I, Imboden M, Rochat T, Henderson J, Sterne JA, McArdle WL, Hui J, James AL, William Musk A, Palmer LJ, Becker A, Kozyrskyj AL, Chan-Young M, Park JE, Leung A, Daley D, Freidin MB, Deev IA, Ogorodova LM, Puzyrev VP, Celedón JC, Brehm JM, Cloutier MM, Canino G, Acosta-Pérez E, Soto-Quiros M, Avila L, Bergström A, Magnusson J, Söderhäll C, Kull I, Scholtens S, Marike Boezen H, Koppelman GH, Wijga AH, Marenholz I, Esparza-Gordillo J, Lau S, Lee YA, Standl M, Tiesler CM, Flexeder C, Heinrich J, Myers RA, Ober C, Nicolae DL, Farrall M, Kumar A, Moffatt MF, Cookson WO, Lasky-Su J. Genome-wide association study of body mass index in 23 000 individuals with and without asthma. Clin Exp Allergy. 2013 Apr;43(4):463-74. doi: 10.1111/cea.12054.
Myers RA, Himes BE, Gignoux CR, Yang JJ, Gauderman WJ, Rebordosa C, Xie J, Torgerson DG, Levin AM, Baurley J, Graves PE, Mathias RA, Romieu I, Roth LA, Conti D, Avila L, Eng C, Vora H, LeNoir MA, Soto-Quiros M, Liu J, Celedón JC, Galanter JM, Farber HJ, Kumar R, Avila PC, Meade K, Serebrisky D, Thyne S, Rodriguez-Cintron W, Rodriguez-Santana JR, Borrell LN, Lemanske RF Jr, Bleecker ER, Meyers DA, London SJ, Barnes KC, Raby BA, Martinez FD, Gilliland FD, Williams LK, Burchard EG, Weiss ST, Nicolae DL, Ober C. Further replication studies of the EVE Consortium meta-analysis identifies 2 asthma risk loci in European Americans. J Allergy Clin Immunol. 2012 Dec;130(6):1294-301. doi: 10.1016/j.jaci.2012.07.054. Epub 2012 Oct 4. Erratum in: J Allergy Clin Immunol. 2013 Nov;132(5):1259. Galanter, Joshua M [added].
Torgerson DG, Ampleford EJ, Chiu GY, Gauderman WJ, Gignoux CR, Graves PE, Himes BE, Levin AM, Mathias RA, Hancock DB, Baurley JW, Eng C, Stern DA, Celedón JC, Rafaels N, Capurso D, Conti DV, Roth LA, Soto-Quiros M, Togias A, Li X, Myers RA, Romieu I, Van Den Berg DJ, Hu D, Hansel NN, Hernandez RD, Israel E, Salam MT, Galanter J, Avila PC, Avila L, Rodriquez-Santana JR, Chapela R, Rodriguez-Cintron W, Diette GB, Adkinson NF, Abel RA, Ross KD, Shi M, Faruque MU, Dunston GM, Watson HR, Mantese VJ, Ezurum SC, Liang L, Ruczinski I, Ford JG, Huntsman S, Chung KF, Vora H, Li X, Calhoun WJ, Castro M, Sienra-Monge JJ, del Rio-Navarro B, Deichmann KA, Heinzmann A, Wenzel SE, Busse WW, Gern JE, Lemanske RF Jr, Beaty TH, Bleecker ER, Raby BA, Meyers DA, London SJ; Mexico City Childhood Asthma Study (MCAAS), Gilliland FD; Children's Health Study (CHS) and HARBORS study, Burchard EG; Genetics of Asthma in Latino Americans (GALA) Study, Study of Genes-Environment and Admixture in Latino Americans (GALA2) and Study of African Americans, Asthma, Genes & Environments (SAGE), Martinez FD; Childhood Asthma Research and Education (CARE) Network, Weiss ST; Childhood Asthma Management Program (CAMP), Williams LK; Study of Asthma Phenotypes and Pharmacogenomic Interactions by Race-Ethnicity (SAPPHIRE), Barnes KC; Genetic Research on Asthma in African Diaspora (GRAAD) Study, Ober C, Nicolae DL. Meta-analysis of genome-wide association studies of asthma in ethnically diverse North American populations. Nat Genet. 2011 Jul 31;43(9):887-92. doi: 10.1038/ng.888.

Layout table for additonal information
Responsible Party: Scott T. Weiss, Professor of Medicine, Brigham and Women's Hospital Identifier: NCT00021840     History of Changes
Other Study ID Numbers: 971
R37HL066289 ( U.S. NIH Grant/Contract )
First Posted: August 7, 2001    Key Record Dates
Last Update Posted: August 4, 2014
Last Verified: August 2014
Additional relevant MeSH terms:
Layout table for MeSH terms
Lung Diseases
Bronchial Diseases
Respiratory Tract Diseases
Lung Diseases, Obstructive
Respiratory Hypersensitivity
Hypersensitivity, Immediate
Immune System Diseases