Genome-wide linkage analysis of pulmonary function in families of children with asthma in Costa Rica
- Craig P Hersh1,
- Manuel E Soto-Quirós2,
- Lydiana Avila2,
- Stephen L Lake1,
- Catherine Liang1,
- Eduardo Fournier2,
- Mitzi Spesny2,
- Jody S Sylvia1,
- Ross Lazarus1,
- Thomas Hudson3,
- Andrei Verner3,
- Barbara J Klanderman1,
- Nelson B Freimer4,
- Edwin K Silverman1,
- Juan C Celedón1
- 1Channing Laboratory, Department of Medicine, Brigham and Women’s Hospital, Boston, Massachusetts, USA
- 2Division of Pediatric Pulmonology, Hospital Nacional de Niños, San José, Costa Rica
- 3McGill University and Genome Quebec Innovation Centre, Montreal, Canada
- 4Department of Psychiatry, University of California at Los Angeles, Los Angeles, California
- Correspondence to:
Dr J C Celedón
Channing Laboratory, Brigham and Women’s Hospital, 181 Longwood Avenue, Boston, MA 02115, USA;
- Received 29 June 2006
- Accepted 27 September 2006
- Published Online First 10 November 2006
Background: Although asthma is highly prevalent among certain Hispanic subgroups, genetic determinants of asthma and asthma-related traits have not been conclusively identified in Hispanic populations. A study was undertaken to identify genomic regions containing susceptibility loci for pulmonary function and bronchodilator responsiveness (BDR) in Costa Ricans.
Methods: Eight extended pedigrees were ascertained through schoolchildren with asthma in the Central Valley of Costa Rica. Short tandem repeat (STR) markers were genotyped throughout the genome at an average spacing of 8.2 cM. Multipoint variance component linkage analyses of forced expiratory volume in 1 second (FEV1) and FEV1/ forced vital capacity (FVC; both pre-bronchodilator and post-bronchodilator) and BDR were performed in these eight families (pre-bronchodilator spirometry, n = 640; post-bronchodilator spirometry and BDR, n = 624). Nine additional STR markers were genotyped on chromosome 7. Secondary analyses were repeated after stratification by cigarette smoking.
Results: Among all subjects, the highest logarithm of the odds of linkage (LOD) score for FEV1 (post-bronchodilator) was found on chromosome 7q34–35 (LOD = 2.45, including the additional markers). The highest LOD scores for FEV1/FVC (pre-bronchodilator) and BDR were found on chromosomes 2q (LOD = 1.53) and 9p (LOD = 1.53), respectively. Among former and current smokers there was near-significant evidence of linkage to FEV1/FVC (post-bronchodilator) on chromosome 5p (LOD = 3.27) and suggestive evidence of linkage to FEV1 on chromosomes 3q (pre-bronchodilator, LOD = 2.74) and 4q (post-bronchodilator, LOD = 2.66).
Conclusions: In eight families of children with asthma in Costa Rica, there is suggestive evidence of linkage to FEV1 on chromosome 7q34–35. In these families, FEV1/FVC may be influenced by an interaction between cigarette smoking and a locus (loci) on chromosome 5p.
- BDR, bronchodilator responsiveness
- COPD, chronic obstructive pulmonary disease
- FEV1, forced expiratory volume in 1 second
- FVC, forced vital capacity
- LOD, logarithm of the odds of linkage
- SOLAR, Sequential Oligogenic Linkage Analysis Routines
- STR, short tandem repeat
Published Online First 10 November 2006
Funding: This work was supported by US National Institutes of Health (NIH) grants HL66289, HL04370 and HL073373. Dr Hersh is supported by NIH grant HL080242 and a grant from the Alpha-1 Foundation. The study sponsors had no role in study design, data collection, data analysis, manuscript preparation or submission.
Competing interests: Edwin K Silverman received grant support, consulting fees and honoraria from GlaxoSmithKline for studies of COPD genetics. He has received a speaker fee from Wyeth for a talk on COPD genetics and has also received honoraria from Bayer. None of the other authors declare any competing interests.