Polymorphisms of chitinases are not associated with asthma
2010; Elsevier BV; Volume: 125; Issue: 3 Linguagem: Inglês
10.1016/j.jaci.2009.12.995
ISSN1097-6825
AutoresAnn Chen Wu, Jessica Lasky‐Su, Christine A. Rogers, Barbara J. Klanderman, Augusto A. Litonjua,
Tópico(s)Insect symbiosis and bacterial influences
ResumoTo the Editor:One of the most exciting findings recently in the pathophysiology of asthma is that mammalian chitinases might play an important role in the pathogenesis of asthma. Some researchers hypothesize that mammalian chitinases and a chitinase homologue might contribute to the pathogenesis of type 2 helper immune responses, which play an important role in asthma.1Chupp G.L. Lee C.G. Jarjour N. Shim Y.M. Holm C.T. He S. et al.A chitinase-like protein in the lung and circulation of patients with severe asthma.N Engl J Med. 2007; 357: 2016-2027Crossref PubMed Scopus (455) Google Scholar, 2Zhu Z. Zheng T. Homer R.J. Kim Y.K. Chen N.Y. Cohn L. et al.Acidic mammalian chitinase in asthmatic Th2 inflammation and IL-13 pathway activation.Science. 2004; 304: 1678-1682Crossref PubMed Scopus (680) Google Scholar Chitinases are enzymes that cleave chitin, a polysaccharide that is present in fungal cells, crustaceans, insects, and parasitic nematodes.3Boot R.G. Blommaart E.F. Swart E. Ghauharali-van der Vlugt K. Bijl N. Moe C. et al.Identification of a novel acidic mammalian chitinase distinct from chitotriosidase.J Biol Chem. 2001; 276: 6770-6778Crossref PubMed Scopus (413) Google Scholar Although chitin does not exist in human subjects, 2 chitinases, acidic mammalian chitinase (CHIA) and chitotriosidase (CHIT1), have been described in human subjects.3Boot R.G. Blommaart E.F. Swart E. Ghauharali-van der Vlugt K. Bijl N. Moe C. et al.Identification of a novel acidic mammalian chitinase distinct from chitotriosidase.J Biol Chem. 2001; 276: 6770-6778Crossref PubMed Scopus (413) Google Scholar A third protein, chitinase-like protein YKL-40 (also known as human cartilage glycoprotein 39 and chitinase 3–like 1 [CHI3L1]), also appears to be important in asthma.1Chupp G.L. Lee C.G. Jarjour N. Shim Y.M. Holm C.T. He S. et al.A chitinase-like protein in the lung and circulation of patients with severe asthma.N Engl J Med. 2007; 357: 2016-2027Crossref PubMed Scopus (455) Google ScholarThe objectives of this study were to assess whether single nucleotide polymorphisms (SNPs) in CHIT1, CHIA, and CHI3L1 and one CHIT1 duplication are associated with asthma, changes in lung physiology that are associated with asthma, or allergy-related phenotypes. We used data from the Childhood Asthma Management Program (CAMP), a multicenter trial that enrolled children between the ages of 5 and 12 years with mild-to-moderate persistent asthma and their parents.4The Childhood Asthma Management Program Research Group Long-term effects of budesonide or nedocromil in children with asthma.N Engl J Med. 2000; 343: 1054-1063Crossref PubMed Scopus (1292) Google Scholar Subjects were followed every 2 to 4 months for 4 years to study the long-term use of budesonide, nedocromil, and placebo.4The Childhood Asthma Management Program Research Group Long-term effects of budesonide or nedocromil in children with asthma.N Engl J Med. 2000; 343: 1054-1063Crossref PubMed Scopus (1292) Google ScholarSNPs in CHIT1, CHIA, and CHI3L1 (see Fig E1 in this article's Online Repository at www.jacionline.org for linkage disequilibrium plots) were genotyped by using the Infinium HumanHap550 genotyping at Illumina (San Diego, Calif). Genotyping quality was evaluated by using the program PLINK (version 1.01). SNPs with low Illumina GenCall scores, poor completion rates, or 4 or more parent-offspring genotyped inconsistencies were dropped. Using the Basic Local Alignment Search Tool, SNPs were further limited to those whose flanking sequences were reliably mapped to unique autosomal locations in the hg17 reference genome sequence. The CHIT1 fragment analysis5Seibold M.A. Donnelly S. Solon M. Innes A. Woodruff P.G. Boot R.G. et al.Chitotriosidase is the primary active chitinase in the human lung and is modulated by genotype and smoking habit.J Allergy Clin Immunol. 2008; 122 (e3): 944-950Abstract Full Text Full Text PDF PubMed Scopus (80) Google Scholar was performed by using the Applied Biosystems (Foster City, Calif) 3100 Genetic Analyzer platform. Primers CHIT1_A1FGTCTGGATGAGGGGGTATCG-FAM and CHIT1 A1RGTTTCTTCCCTGCACAGGTCAGCTATC were used to PCR amplify the region containing the 24-bp duplication, and peaks were analyzed with Applied Biosystems GeneMapper software. The genotyping completion rate was 94%.Family-Based Association Test–Principal Components (FBAT-PC) is a method that has the ability to use genetic data from family members to assess associations between a disease phenotype and a gene allele while maximizing the genetic information when multiple phenotypes are tested.6Lasky-Su J. Biederman J. Doyle A.E. Wilens T. Monuteaux M. Smoller J.W. et al.Family based association analysis of statistically derived quantitative traits for drug use in ADHD and the dopamine transporter gene.Addict Behav. 2006; 31: 1088-1099Crossref PubMed Scopus (7) Google Scholar We performed association analyses for each SNP and each phenotype using the FBAT-PC approach. FBAT-PC uses principal components analysis to construct an overall phenotype that amplifies the trait heritability by aggregating the genetic components of all measurements into a single univariate phenotype with maximal heritability.6Lasky-Su J. Biederman J. Doyle A.E. Wilens T. Monuteaux M. Smoller J.W. et al.Family based association analysis of statistically derived quantitative traits for drug use in ADHD and the dopamine transporter gene.Addict Behav. 2006; 31: 1088-1099Crossref PubMed Scopus (7) Google ScholarAfter the univariate phenotype is generated at each SNP, FBAT-PC uses a screening procedure to select the SNPs to be tested by using a univariate quantitative FBAT statistic, the FBAT-PC statistic. For each SNP, the power to detect the association with the generated univariate phenotype is calculated, a group of SNPs with their associated phenotypes are selected based on the power to detect a genetic association, and then the FBAT-PC statistic is calculated on the SNPs and their associated phenotypes. In the analysis for this study, the additive genetic model was used, and a minimum of 20 informative families were required. We used an FBAT approach with generalized estimating equations7Lange C. Silverman E.K. Xu X. Weiss S.T. Laird N.M. A multivariate family-based association test using generalized estimating equations: FBAT-GEE.Biostatistics. 2003; 4: 195-206Crossref PubMed Scopus (156) Google Scholar for our outcomes, which were assessed at one time point.Power calculations were conducted by using the FBAT Power Calculator (HelixTree version 6.4.2, 2008; see Table E1 in this article's Online Repository at www.jacionline.org). Assuming a significance level of .05, we had an 80% or greater power to detect an association between each SNP and a single continuous measure for a heritability of 4% or greater. We had greater power to detect smaller effect sizes for our outcomes with repeated measures. For example, we had an 80% or greater power to detect an association for a heritability of 4% or greater for the outcomes FEV1 and FEV1 percent predicted, which had 16 repeated measures.Table I provides the baseline demographic characteristics measured in our study population of 422 children. None of the polymorphisms were associated with asthma after Bonferroni correction. We found no associations between the SNPs and the total number of hospitalizations and emergency department visits over 4 years (Table II). The results were not significantly different after adjusting for age, sex, and treatment group.Table IDemographics (n = 422)Age (y [range])8.7 (2.1 [5.2-13.2])Treatment group Budesonide28% (118) Nedocromil29% (122) Placebo43% (182)Sex, n = 422 Male63% (266) Female37% (156)Weight at baseline (kg), n = 41931.87 (10.56)Height at baseline (cm), n = 417132.45 (13.50)Total number of hospitalization and ED visits over 4-y period, n = 422 069% (291) 114% (60) 27% (31) ≥39.5% (40)Baseline pre-FEV1, n = 4211.694 (0.473)Baseline bronchodilator Response, n = 4210.104 (0.098)Baseline FEV1 percent predicted, n = 41693.370 (13.954)Baseline lnPC20, n = 4200.025 (1.153)Baseline log10 IgE level, n = 4172.616 (0.671)Baseline log10 eosinophil count, n = 4142.561 (0.488)Values are presented as means (SDs) or percentages (numbers), where shown.ED, Emergency department. Open table in a new tab Table IIFBAT-PC results from the SNPs using the PBAT Power ScreenUnadjusted FBAT-PC P value∗The results were not significantly different, even after adjusting for age, sex, and treatment group.GeneMarkerMinor allele frequencyNo. of informative familiesPre-FEV1BDRlnPC20log10 Eosinophil countlog10 IgE levelTotal no. of hospitalizations and ED visitsCHIT1rs49509340.108161.036.526.879.221.715.144rs24869530.473341.403.483.080.175.084.646rs24869540.196251.233.570.590.776.117.299rs121413750.197252.221.621.573.774.107.282rs49509360.474341.443.524.083.170.121.640rs49509370.280276.697.854.752.089.699.668rs8725830.195253.262.728.694.796.050.239rs14171490.471340.441.609.079.106.096.679rs3831317†rs3831317 is a 24-bp duplication in CHIT1.0.174273.913.693.799.490.420.922rs24869580.492340.570.753.102.935.872.591rs15568540.485341.516.697.087.560.815.556rs24869590.174235.263.775.837.702.244.265rs9462570.309290.387.913.372.860.325.951rs24860680.171234.275.875.724.868.223.253rs22979500.308289.456.886.676.746.233.984rs24860700.171233.312.840.702.799.209.269rs37665370.192241.218.148.842.117.106.957rs14171500.467331.781.970.177.237.077.305rs24860720.353323.703.533.784.471.098.844rs127471100.01428.774.567.427.405.896.798rs24942870.128177.149.937.348.602.529.999CHIArs42405290.283222.256.622.538.594.331.589rs42726220.190167.126.900.369.018.049.178rs111022330.258208.052.839.101.167.466.550rs124017370.460264.979.078.764.992.028.172rs108578710.212188.847.514.787.493.091.146rs38064480.481261.844.293.891.930.527.666rs104941320.221208.449.263.378.234.257.072rs38064460.450270.590.651.868.891.510.331rs74113870.401239.978.319.775.018.018.064rs115842910.313243.940.502.691.144.191.636rs42405300.288245.533.779.777.060.213.758rs121273130.136149.487.477.625.870.261.214rs104941330.143159.188.417.528.036.039.362rs38188220.101124.547.714.592.395.930.906rs120345760.326242.567.007.610.860.566.524rs104941340.463269.058.000.204.807.631.805rs22752530.288236.603.692.577.028.501.751rs22752540.396261.679.011.400.493.645.718rs22567210.286225.708.764.593.050.432.787rs28200930.102126.663.857.515.457.716.877rs22822900.469267.576.119.767.077.253.268rs120341770.328241.562.007.597.858.558.534rs107767240.454262.815.232.958.088.560.156rs121376970.128141.840.724.594.935.075.105CH13L1rs75422940.145168.953.616.171.985.257.797rs8806330.485254.130.436.007.560.272.903rs103998050.126149.448.999.047.757.060.192rs9462610.401252.200.687.010.811.291.970ED, Emergency department.∗ The results were not significantly different, even after adjusting for age, sex, and treatment group.† rs3831317 is a 24-bp duplication in CHIT1. Open table in a new tab Although there is increasing evidence that chitinases play a role in asthma, our analysis suggests that variations in chitinase genes are not associated with asthma. Our study found no associations between SNPs in the genes CHIT1, CHIA, and CHI3L1 and any of the outcomes studied: asthma, changes in lung physiology, or allergy-related phenotypes in subjects with mild-to-moderate asthma. Another strength of our study was the use of repeated measures of the asthma- and allergy-related phenotypes using a family-based design that accounts for these repeated measures, thus providing greater power to detect associations than a single measurement of the outcome.Our finding that SNPs in CHIT1 and CHI3L1 are not associated with asthma is consistent with the findings of other studies.8Bierbaum S. Superti-Furga A. Heinzmann A. Genetic polymorphisms of chitotriosidase in Caucasian children with bronchial asthma.Int J Immunogenet. 2006; 33: 201-204Crossref PubMed Scopus (28) Google Scholar, 9Sohn M.H. Lee J.H. Kim K.W. Kim S.W. Lee S.H. Kim K.E. et al.Genetic variation in the promoter region of chitinase 3-like 1 is associated with atopy.Am J Respir Crit Care Med. 2009; 179: 449-456Crossref PubMed Scopus (67) Google Scholar On the other hand, our study findings are in contrast to previous studies that found that polymorphisms in CHIA are associated with asthma and IgE levels10Bierbaum S. Nickel R. Koch A. Lau S. Deichmann K.A. Wahn U. et al.Polymorphisms and haplotypes of acid mammalian chitinase are associated with bronchial asthma.Am J Respir Crit Care Med. 2005; 172: 1505-1509Crossref PubMed Scopus (107) Google Scholar, 11Chatterjee R. Batra J. Das S. Sharma S.K. Ghosh B. Genetic association of acidic mammalian chitinase with atopic asthma and serum total IgE levels.J Allergy Clin Immunol. 2008; 122 (e1-7): 202-208Abstract Full Text Full Text PDF PubMed Scopus (49) Google Scholar and a previous study that concluded that CHI3L1 is associated with asthma.12Ober C. Tan Z. Sun Y. Possick J.D. Pan L. Nicolae R. et al.Effect of variation in CHI3L1 on serum YKL-40 level, risk of asthma, and lung function.N Engl J Med. 2008; 358: 1682-1691Crossref PubMed Scopus (403) Google Scholar One potential reason for the discrepant findings might be that the studies that found positive associations used a case-control design, did not evaluate for population stratification, or did not adjust for multiple testing. Alternatively, environmental exposures in our cohort interacting with these genes might be different than in other cohorts.Despite the strengths of our study, we were limited by our relatively small sample size of 422 subjects. Nevertheless, our power calculations suggest we had adequate power to detect small-to-moderate effect sizes.The human chitinases and chitinase-like proteins have received attention in recent years because of their potential role in the pathogenesis of asthma. Nevertheless, polymorphisms in CHIT1, CHIA, and CHI3L1 are not associated with asthma, changes in lung physiology, or allergy-related phenotypes, suggesting that the effects of variation in these genes alone are weak without the appropriate environmental exposure. To the Editor: One of the most exciting findings recently in the pathophysiology of asthma is that mammalian chitinases might play an important role in the pathogenesis of asthma. Some researchers hypothesize that mammalian chitinases and a chitinase homologue might contribute to the pathogenesis of type 2 helper immune responses, which play an important role in asthma.1Chupp G.L. Lee C.G. Jarjour N. Shim Y.M. Holm C.T. He S. et al.A chitinase-like protein in the lung and circulation of patients with severe asthma.N Engl J Med. 2007; 357: 2016-2027Crossref PubMed Scopus (455) Google Scholar, 2Zhu Z. Zheng T. Homer R.J. Kim Y.K. Chen N.Y. Cohn L. et al.Acidic mammalian chitinase in asthmatic Th2 inflammation and IL-13 pathway activation.Science. 2004; 304: 1678-1682Crossref PubMed Scopus (680) Google Scholar Chitinases are enzymes that cleave chitin, a polysaccharide that is present in fungal cells, crustaceans, insects, and parasitic nematodes.3Boot R.G. Blommaart E.F. Swart E. Ghauharali-van der Vlugt K. Bijl N. Moe C. et al.Identification of a novel acidic mammalian chitinase distinct from chitotriosidase.J Biol Chem. 2001; 276: 6770-6778Crossref PubMed Scopus (413) Google Scholar Although chitin does not exist in human subjects, 2 chitinases, acidic mammalian chitinase (CHIA) and chitotriosidase (CHIT1), have been described in human subjects.3Boot R.G. Blommaart E.F. Swart E. Ghauharali-van der Vlugt K. Bijl N. Moe C. et al.Identification of a novel acidic mammalian chitinase distinct from chitotriosidase.J Biol Chem. 2001; 276: 6770-6778Crossref PubMed Scopus (413) Google Scholar A third protein, chitinase-like protein YKL-40 (also known as human cartilage glycoprotein 39 and chitinase 3–like 1 [CHI3L1]), also appears to be important in asthma.1Chupp G.L. Lee C.G. Jarjour N. Shim Y.M. Holm C.T. He S. et al.A chitinase-like protein in the lung and circulation of patients with severe asthma.N Engl J Med. 2007; 357: 2016-2027Crossref PubMed Scopus (455) Google Scholar The objectives of this study were to assess whether single nucleotide polymorphisms (SNPs) in CHIT1, CHIA, and CHI3L1 and one CHIT1 duplication are associated with asthma, changes in lung physiology that are associated with asthma, or allergy-related phenotypes. We used data from the Childhood Asthma Management Program (CAMP), a multicenter trial that enrolled children between the ages of 5 and 12 years with mild-to-moderate persistent asthma and their parents.4The Childhood Asthma Management Program Research Group Long-term effects of budesonide or nedocromil in children with asthma.N Engl J Med. 2000; 343: 1054-1063Crossref PubMed Scopus (1292) Google Scholar Subjects were followed every 2 to 4 months for 4 years to study the long-term use of budesonide, nedocromil, and placebo.4The Childhood Asthma Management Program Research Group Long-term effects of budesonide or nedocromil in children with asthma.N Engl J Med. 2000; 343: 1054-1063Crossref PubMed Scopus (1292) Google Scholar SNPs in CHIT1, CHIA, and CHI3L1 (see Fig E1 in this article's Online Repository at www.jacionline.org for linkage disequilibrium plots) were genotyped by using the Infinium HumanHap550 genotyping at Illumina (San Diego, Calif). Genotyping quality was evaluated by using the program PLINK (version 1.01). SNPs with low Illumina GenCall scores, poor completion rates, or 4 or more parent-offspring genotyped inconsistencies were dropped. Using the Basic Local Alignment Search Tool, SNPs were further limited to those whose flanking sequences were reliably mapped to unique autosomal locations in the hg17 reference genome sequence. The CHIT1 fragment analysis5Seibold M.A. Donnelly S. Solon M. Innes A. Woodruff P.G. Boot R.G. et al.Chitotriosidase is the primary active chitinase in the human lung and is modulated by genotype and smoking habit.J Allergy Clin Immunol. 2008; 122 (e3): 944-950Abstract Full Text Full Text PDF PubMed Scopus (80) Google Scholar was performed by using the Applied Biosystems (Foster City, Calif) 3100 Genetic Analyzer platform. Primers CHIT1_A1FGTCTGGATGAGGGGGTATCG-FAM and CHIT1 A1RGTTTCTTCCCTGCACAGGTCAGCTATC were used to PCR amplify the region containing the 24-bp duplication, and peaks were analyzed with Applied Biosystems GeneMapper software. The genotyping completion rate was 94%. Family-Based Association Test–Principal Components (FBAT-PC) is a method that has the ability to use genetic data from family members to assess associations between a disease phenotype and a gene allele while maximizing the genetic information when multiple phenotypes are tested.6Lasky-Su J. Biederman J. Doyle A.E. Wilens T. Monuteaux M. Smoller J.W. et al.Family based association analysis of statistically derived quantitative traits for drug use in ADHD and the dopamine transporter gene.Addict Behav. 2006; 31: 1088-1099Crossref PubMed Scopus (7) Google Scholar We performed association analyses for each SNP and each phenotype using the FBAT-PC approach. FBAT-PC uses principal components analysis to construct an overall phenotype that amplifies the trait heritability by aggregating the genetic components of all measurements into a single univariate phenotype with maximal heritability.6Lasky-Su J. Biederman J. Doyle A.E. Wilens T. Monuteaux M. Smoller J.W. et al.Family based association analysis of statistically derived quantitative traits for drug use in ADHD and the dopamine transporter gene.Addict Behav. 2006; 31: 1088-1099Crossref PubMed Scopus (7) Google Scholar After the univariate phenotype is generated at each SNP, FBAT-PC uses a screening procedure to select the SNPs to be tested by using a univariate quantitative FBAT statistic, the FBAT-PC statistic. For each SNP, the power to detect the association with the generated univariate phenotype is calculated, a group of SNPs with their associated phenotypes are selected based on the power to detect a genetic association, and then the FBAT-PC statistic is calculated on the SNPs and their associated phenotypes. In the analysis for this study, the additive genetic model was used, and a minimum of 20 informative families were required. We used an FBAT approach with generalized estimating equations7Lange C. Silverman E.K. Xu X. Weiss S.T. Laird N.M. A multivariate family-based association test using generalized estimating equations: FBAT-GEE.Biostatistics. 2003; 4: 195-206Crossref PubMed Scopus (156) Google Scholar for our outcomes, which were assessed at one time point. Power calculations were conducted by using the FBAT Power Calculator (HelixTree version 6.4.2, 2008; see Table E1 in this article's Online Repository at www.jacionline.org). Assuming a significance level of .05, we had an 80% or greater power to detect an association between each SNP and a single continuous measure for a heritability of 4% or greater. We had greater power to detect smaller effect sizes for our outcomes with repeated measures. For example, we had an 80% or greater power to detect an association for a heritability of 4% or greater for the outcomes FEV1 and FEV1 percent predicted, which had 16 repeated measures. Table I provides the baseline demographic characteristics measured in our study population of 422 children. None of the polymorphisms were associated with asthma after Bonferroni correction. We found no associations between the SNPs and the total number of hospitalizations and emergency department visits over 4 years (Table II). The results were not significantly different after adjusting for age, sex, and treatment group. Values are presented as means (SDs) or percentages (numbers), where shown. ED, Emergency department. ED, Emergency department. Although there is increasing evidence that chitinases play a role in asthma, our analysis suggests that variations in chitinase genes are not associated with asthma. Our study found no associations between SNPs in the genes CHIT1, CHIA, and CHI3L1 and any of the outcomes studied: asthma, changes in lung physiology, or allergy-related phenotypes in subjects with mild-to-moderate asthma. Another strength of our study was the use of repeated measures of the asthma- and allergy-related phenotypes using a family-based design that accounts for these repeated measures, thus providing greater power to detect associations than a single measurement of the outcome. Our finding that SNPs in CHIT1 and CHI3L1 are not associated with asthma is consistent with the findings of other studies.8Bierbaum S. Superti-Furga A. Heinzmann A. Genetic polymorphisms of chitotriosidase in Caucasian children with bronchial asthma.Int J Immunogenet. 2006; 33: 201-204Crossref PubMed Scopus (28) Google Scholar, 9Sohn M.H. Lee J.H. Kim K.W. Kim S.W. Lee S.H. Kim K.E. et al.Genetic variation in the promoter region of chitinase 3-like 1 is associated with atopy.Am J Respir Crit Care Med. 2009; 179: 449-456Crossref PubMed Scopus (67) Google Scholar On the other hand, our study findings are in contrast to previous studies that found that polymorphisms in CHIA are associated with asthma and IgE levels10Bierbaum S. Nickel R. Koch A. Lau S. Deichmann K.A. Wahn U. et al.Polymorphisms and haplotypes of acid mammalian chitinase are associated with bronchial asthma.Am J Respir Crit Care Med. 2005; 172: 1505-1509Crossref PubMed Scopus (107) Google Scholar, 11Chatterjee R. Batra J. Das S. Sharma S.K. Ghosh B. Genetic association of acidic mammalian chitinase with atopic asthma and serum total IgE levels.J Allergy Clin Immunol. 2008; 122 (e1-7): 202-208Abstract Full Text Full Text PDF PubMed Scopus (49) Google Scholar and a previous study that concluded that CHI3L1 is associated with asthma.12Ober C. Tan Z. Sun Y. Possick J.D. Pan L. Nicolae R. et al.Effect of variation in CHI3L1 on serum YKL-40 level, risk of asthma, and lung function.N Engl J Med. 2008; 358: 1682-1691Crossref PubMed Scopus (403) Google Scholar One potential reason for the discrepant findings might be that the studies that found positive associations used a case-control design, did not evaluate for population stratification, or did not adjust for multiple testing. Alternatively, environmental exposures in our cohort interacting with these genes might be different than in other cohorts. Despite the strengths of our study, we were limited by our relatively small sample size of 422 subjects. Nevertheless, our power calculations suggest we had adequate power to detect small-to-moderate effect sizes. The human chitinases and chitinase-like proteins have received attention in recent years because of their potential role in the pathogenesis of asthma. Nevertheless, polymorphisms in CHIT1, CHIA, and CHI3L1 are not associated with asthma, changes in lung physiology, or allergy-related phenotypes, suggesting that the effects of variation in these genes alone are weak without the appropriate environmental exposure. We thank Brooke Schuemann, MPH, for her assistance with preparation of the phenotype data. We thank all subjects for their ongoing participation in this study. We acknowledge the CAMP investigators and research team, supported by the National Heart, Lung, and Blood Institute , for collection of CAMP Genetic Ancillary Study data. All work on data collected from the CAMP Genetic Ancillary Study was conducted at Channing Laboratory of the Brigham and Women's Hospital under appropriate CAMP policies and human subject's protections. CAMP is supported by U01 HL076419 , U01 HL65899 , P01 HL083069 , and T32 HL07427 from the National Heart, Lung, and Blood Institute, National Institutes of Health . Fig E1. Table E1. Tabled 1Power for varying numbers of repeated measures and heritabilityHeritabilityPower2%3%4%6%10%No. of repeated measures 10.520.690.810.941.00 2 (log10 IgE level and log10 eosinophil count had 2 repeated measures)0.650.810.910.981.00 5 (lnPC20 had 5 repeated measures)0.961.001.001.001.00 10 (BDR had 10 repeated measures)1.001.001.001.001.00 16 (FEV1 had 16 repeated measures)1.001.001.001.001.00Calculations assume an allele frequency of 10% and an α value of .05. Open table in a new tab Calculations assume an allele frequency of 10% and an α value of .05.
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