Immunogenetics

, Volume 68, Issue 6–7, pp 391–400 | Cite as

Novel genetic risk factors for asthma in African American children: Precision Medicine and the SAGE II Study

  • Marquitta J. White
  • O. Risse-Adams
  • P. Goddard
  • M. G. Contreras
  • J. Adams
  • D. Hu
  • C. Eng
  • S. S. Oh
  • A. Davis
  • K. Meade
  • E. Brigino-Buenaventura
  • M. A. LeNoir
  • K. Bibbins-Domingo
  • M. Pino-Yanes
  • E. G. Burchard
Original Article

Abstract

Asthma, an inflammatory disorder of the airways, is the most common chronic disease of children worldwide. There are significant racial/ethnic disparities in asthma prevalence, morbidity, and mortality among US children. This trend is mirrored in obesity, which may share genetic and environmental risk factors with asthma. The majority of asthma biomedical research has been performed in populations of European decent. We sought to identify genetic risk factors for asthma in African American children. We also assessed the generalizability of genetic variants associated with asthma in European and Asian populations to African American children. Our study population consisted of 1227 (812 asthma cases, 415 controls) African American children with genome-wide single nucleotide polymorphism (SNP) data. Logistic regression was used to identify associations between SNP genotype and asthma status. We identified a novel variant in the PTCHD3 gene that is significantly associated with asthma (rs660498, p = 2.2 × 10−7) independent of obesity status. Approximately 5 % of previously reported asthma genetic associations identified in European populations replicated in African Americans. Our identification of novel variants associated with asthma in African American children, coupled with our inability to replicate the majority of findings reported in European Americans, underscores the necessity for including diverse populations in biomedical studies of asthma.

Keywords

Health disparities Children Asthma Genetics GWAS 

Supplementary material

251_2016_914_Fig4_ESM.gif (23 kb)
Figure S1

Post-hoc Power Calculations for Detectable Effect Sizes in the SAGE II population. (GIF 22 kb)

251_2016_914_MOESM1_ESM.tif (161 kb)
High Resolution Image (TIF 161 kb)
251_2016_914_MOESM2_ESM.docx (15 kb)
ESM 1(DOCX 14 kb)
251_2016_914_MOESM3_ESM.docx (38 kb)
ESM 2(DOCX 37 kb)

References

  1. Acock AC (2014) A gentle introduction to stata. Stata Press, College StationGoogle Scholar
  2. Akhabir L, Sandford AJ (2011) Genome-wide association studies for discovery of genes involved in asthma. Respirology 16:396–406CrossRefPubMedGoogle Scholar
  3. Akinbami LJ, Moorman JE, Simon AE, Schoendorf KC (2014) Trends in racial disparities for asthma outcomes among children 0 to 17 years, 2001–2010. J Allergy Clin Immunol 134(547–553), e5PubMedGoogle Scholar
  4. Alexander DH, Novembre J, Lange K (2009) Fast model-based estimation of ancestry in unrelated individuals. Genome Res 19:1655–1664CrossRefPubMedPubMedCentralGoogle Scholar
  5. Barnes PJ (2001) Th2 cytokines and asthma: an introduction. Respir Res 2:64–65CrossRefPubMedPubMedCentralGoogle Scholar
  6. Borrell LN, Nguyen EA, Roth LA, Oh SS, Tcheurekdjian H, Sen S, Davis A, Farber HJ, Avila PC, Brigino-Buenaventura E, Lenoir MA, Lurmann F, Meade K, Serebrisky D, Rodriguez-Cintron W, Kumar R, Rodriguez-Santana JR, Thyne SM, Burchard EG (2013) Childhood obesity and asthma control in the GALA II and SAGE II studies. Am J Respir Crit Care Med 187:697–702CrossRefPubMedPubMedCentralGoogle Scholar
  7. Burchard EG (2014) Medical research: missing patients. Nature 513:301–302CrossRefPubMedGoogle Scholar
  8. Burchard EG, Oh SS, Foreman MG, Celedon JC (2015) Moving toward true inclusion of racial/ethnic minorities in federally funded studies. A key step for achieving respiratory health equality in the United States. Am J Respir Crit Care Med 191:514–521CrossRefPubMedPubMedCentralGoogle Scholar
  9. Burdett TE, Hall PN (NHGRI), Hasting E (EBI), Hindorff LA (NHGRI), Junkins HA (NHGRI), Kiemm AK (NHGRI), MacArthur J (EBI), Manolio TA (NHGRI), Morales J (EBI), Parkinson H (EBI), Welter D (EBI) (2014) The NHGRI-EBI Catalog of published genome-wide association studies. www.ebi.ac.uk/gwas. Accessed 3 Feb 2016
  10. Bustamante CD, Burchard EG, De la Vega FM (2011) Genomics for the world. Nature 475:163–165CrossRefPubMedPubMedCentralGoogle Scholar
  11. Castro-Giner F, de Cid R, Gonzalez JR, Jarvis D, Heinrich J, Janson C, Omenaas ER, Matheson MC, Pin I, Anto JM, Wjst M, Estivill X, Kogevinas M (2010) Positionally cloned genes and age-specific effects in asthma and atopy: an international population-based cohort study (ECRHS). Thorax 65:124–131CrossRefPubMedGoogle Scholar
  12. Center for Disease Control and Prevention (2014) How is BMI calculated? http://www.cdc.gov/healthyweight/assessing/bmi/adult_bmi/. Accessed 4 Oct 2015
  13. Chang CC, Chow CC, Tellier LC, Vattikuti S, Purcell SM, Lee JJ (2015) Second-generation PLINK: rising to the challenge of larger and richer datasets. Gigascience 4:7CrossRefPubMedPubMedCentralGoogle Scholar
  14. Delaneau O, Marchini J, Zagury JF (2012) A linear complexity phasing method for thousands of genomes. Nat Methods 9:179–181CrossRefGoogle Scholar
  15. Development Core Team R (2010) R: a language and environment for statistical computing. R Foundation for Statistical Computing, ViennaGoogle Scholar
  16. Drake KA, Torgerson DG, Gignoux CR, Galanter JM, Roth LA, Huntsman S, Eng C, Oh SS, Yee SW, Lin L, Bustamante CD, Moreno-Estrada A, Sandoval K, Davis A, Borrell LN, Farber HJ, Kumar R, Avila PC, Brigino-Buenaventura E, Chapela R, Ford JG, Lenoir MA, Lurmann F, Meade K, Serebrisky D, Thyne S, Rodriguez-Cintron W, Sen S, Rodriguez-Santana JR, Hernandez RD, Giacomini KM, Burchard EG (2014) A genome-wide association study of bronchodilator response in Latinos implicates rare variants. J Allergy Clin Immunol 133:370–378CrossRefPubMedGoogle Scholar
  17. Fagnani C, Annesi-Maesano I, Brescianini S, D’Ippolito C, Medda E, Nistico L, Patriarca V, Rotondi D, Toccaceli V, Stazi MA (2008) Heritability and shared genetic effects of asthma and hay fever: an Italian study of young twins. Twin Res Hum Genet 11:121–131CrossRefPubMedGoogle Scholar
  18. Fahy JV (2015) Type 2 inflammation in asthma—present in most, absent in many. Nat Rev Immunol 15:57–65CrossRefPubMedPubMedCentralGoogle Scholar
  19. Furmanski AL, Saldana JI, Ono M, Sahni H, Paschalidis N, D’Acquisto F, Crompton T (2013) Tissue-derived hedgehog proteins modulate Th differentiation and disease. J Immunol 190:2641–2649CrossRefPubMedPubMedCentralGoogle Scholar
  20. Galanter JM, Gignoux CR, Torgerson DG, Roth LA, Eng C, Oh SS, Nguyen EA, Drake KA, Huntsman S, Hu D, Sen S, Davis A, Farber HJ, Avila PC, Brigino-Buenaventura E, LeNoir MA, Meade K, Serebrisky D, Borrell LN, Rodriguez-Cintron W, Estrada AM, Mendoza KS, Winkler CA, Klitz W, Romieu I, London SJ, Gilliland F, Martinez F, Bustamante C, Williams LK, Kumar R, Rodriguez-Santana JR, Burchard EG (2014) Genome-wide association study and admixture mapping identify different asthma-associated loci in Latinos: the Genes-environments & Admixture in Latino Americans study. J Allergy Clin Immunol 134:295–305CrossRefPubMedPubMedCentralGoogle Scholar
  21. Genomes Project C, Abecasis GR, Altshuler D, Auton A, Brooks LD, Durbin RM, Gibbs RA, Hurles ME, McVean GA (2010) A map of human genome variation from population-scale sequencing. Nature 467:1061–1073CrossRefGoogle Scholar
  22. Ghahramani Seno MM, Kwan BY, Lee-Ng KK, Moessner R, Lionel AC, Marshall CR, Scherer SW (2011) Human PTCHD3 nulls: rare copy number and sequence variants suggest a non-essential gene. BMC Med Genet 12:45CrossRefPubMedPubMedCentralGoogle Scholar
  23. Global Asthma Network (2014) The Global Asthma Report 2014. Auckland, New ZealandGoogle Scholar
  24. Gonzalez JR, Caceres A, Esko T, Cusco I, Puig M, Esnaola M, Reina J, Siroux V, Bouzigon E, Nadif R, Reinmaa E, Milani L, Bustamante M, Jarvis D, Anto JM, Sunyer J, Demenais F, Kogevinas M, Metspalu A, Caceres M, Perez-Jurado LA (2014) A common 16p11.2 inversion underlies the joint susceptibility to asthma and obesity. Am J Hum Genet 94:361–372CrossRefPubMedPubMedCentralGoogle Scholar
  25. Gorina Y (2012) QuickStats: asthma* death rates, by race and age group - United States, 2007–2009. In (MMWR) MaMWR (ed.). Centers for Disease Control and PreventionGoogle Scholar
  26. Guerrero AD, Mao C, Fuller B, Bridges M, Franke T, Kuo AA (2016) Racial and ethnic disparities in early childhood obesity: growth trajectories in body mass index. J Racial Ethn Health Disparities 3:129–137CrossRefPubMedGoogle Scholar
  27. Hoffjan S, Nicolae D, Ober C (2003) Association studies for asthma and atopic diseases: a comprehensive review of the literature. Respir Res 4:14CrossRefPubMedPubMedCentralGoogle Scholar
  28. Hoffmann TJ, Zhan Y, Kvale MN, Hesselson SE, Gollub J, Iribarren C, Lu Y, Mei G, Purdy MM, Quesenberry C, Rowell S, Shapero MH, Smethurst D, Somkin CP, Van den Eeden SK, Walter L, Webster T, Whitmer RA, Finn A, Schaefer C, Kwok PY, Risch N (2011) Design and coverage of high throughput genotyping arrays optimized for individuals of East Asian, African American, and Latino race/ethnicity using imputation and a novel hybrid SNP selection algorithm. Genomics 98:422–430CrossRefPubMedPubMedCentralGoogle Scholar
  29. Howie BN, Donnelly P, Marchini J (2009) A flexible and accurate genotype imputation method for the next generation of genome-wide association studies. PLoS Genet 5, e1000529CrossRefPubMedPubMedCentralGoogle Scholar
  30. Howie B, Marchini J, Stephens M (2011) Genotype imputation with thousands of genomes. G3 (Bethesda) 1:457–70CrossRefGoogle Scholar
  31. Imai K, Keele L, Tingley D (2010) A general approach to causal mediation analysis. Psychol Methods 15:309–334CrossRefPubMedGoogle Scholar
  32. International HapMap C, Altshuler DM, Gibbs RA, Peltonen L, Altshuler DM, Gibbs RA, Peltonen L, Dermitzakis E, Schaffner SF, Yu F, Peltonen L, Dermitzakis E, Bonnen PE, Altshuler DM, Gibbs RA, de Bakker PI, Deloukas P, Gabriel SB, Gwilliam R, Hunt S, Inouye M, Jia X, Palotie A, Parkin M, Whittaker P, Yu F, Chang K, Hawes A, Lewis LR, Ren Y, Wheeler D, Gibbs RA, Muzny DM, Barnes C, Darvishi K, Hurles M, Korn JM, Kristiansson K, Lee C, McCarrol SA, Nemesh J, Dermitzakis E, Keinan A, Montgomery SB, Pollack S, Price AL, Soranzo N, Bonnen PE, Gibbs RA, Gonzaga-Jauregui C, Keinan A, Price AL, Yu F, Anttila V, Brodeur W, Daly MJ, Leslie S, McVean G, Moutsianas L, Nguyen H, Schaffner SF, Zhang Q, Ghori MJ, McGinnis R, McLaren W, Pollack S, Price AL, Schaffner SF, Takeuchi F, Grossman SR, Shlyakhter I, Hostetter EB, Sabeti PC, Adebamowo CA, Foster MW, Gordon DR, Licinio J, Manca MC, Marshall PA, Matsuda I, Ngare D, Wang VO, Reddy D, Rotimi CN, Royal CD, Sharp RR, Zeng C, Brooks LD, McEwen JE (2010) Integrating common and rare genetic variation in diverse human populations. Nature 467:52–58CrossRefGoogle Scholar
  33. Joseph M, Elliott M, Zelicoff A, Qian Z, Trevathan E, Chang JJ (2016) Racial disparity in the association between body mass index and self-reported asthma in children: a population-based study. J Asthma:17Google Scholar
  34. Lloyd CM, Hessel EM (2010) Functions of T cells in asthma: more than just T(H)2 cells. Nat Rev Immunol 10:838–848CrossRefPubMedGoogle Scholar
  35. Manning AK, Hivert MF, Scott RA, Grimsby JL, Bouatia-Naji N, Chen H, Rybin D, Liu CT, Bielak LF, Prokopenko I, Amin N, Barnes D, Cadby G, Hottenga JJ, Ingelsson E, Jackson AU, Johnson T, Kanoni S, Ladenvall C, Lagou V, Lahti J, Lecoeur C, Liu Y, Martinez-Larrad MT, Montasser ME, Navarro P, Perry JR, Rasmussen-Torvik LJ, Salo P, Sattar N, Shungin D, Strawbridge RJ, Tanaka T, van Duijn CM, An P, de Andrade M, Andrews JS, Aspelund T, Atalay M, Aulchenko Y, Balkau B, Bandinelli S, Beckmann JS, Beilby JP, Bellis C, Bergman RN, Blangero J, Boban M, Boehnke M, Boerwinkle E, Bonnycastle LL, Boomsma DI, Borecki IB, Bottcher Y, Bouchard C, Brunner E, Budimir D, Campbell H, Carlson O, Chines PS, Clarke R, Collins FS, Corbaton-Anchuelo A, Couper D, de Faire U, Dedoussis GV, Deloukas P, Dimitriou M, Egan JM, Eiriksdottir G, Erdos MR, Eriksson JG, Eury E, Ferrucci L, Ford I, Forouhi NG, Fox CS, Franzosi MG, Franks PW, Frayling TM, Froguel P, Galan P, de Geus E, Gigante B, Glazer NL, Goel A, Groop L, Gudnason V, Hallmans G, Hamsten A, Hansson O, Harris TB, Hayward C, Heath S, Hercberg S, Hicks AA, Hingorani A, Hofman A, Hui J, Hung J et al (2012) A genome-wide approach accounting for body mass index identifies genetic variants influencing fasting glycemic traits and insulin resistance. Nat Genet 44:659–669CrossRefPubMedPubMedCentralGoogle Scholar
  36. McGarry ME, Castellanos E, Thakur N, Oh SS, Eng C, Davis A, Meade K, LeNoir MA, Avila PC, Farber HJ, Serebrisky D, Brigino-Buenaventura E, Rodriguez-Cintron W, Kumar R, Bibbins-Domingo K, Thyne SM, Sen S, Rodriguez-Santana JR, Borrell LN, Burchard EG (2015) Obesity and bronchodilator response in black and Hispanic children and adolescents with asthma. Chest 147:1591–1598CrossRefPubMedPubMedCentralGoogle Scholar
  37. McGeachie MJ, Stahl EA, Himes BE, Pendergrass SA, Lima JJ, Irvin CG, Peters SP, Ritchie MD, Plenge RM, Tantisira KG (2013) Polygenic heritability estimates in pharmacogenetics: focus on asthma and related phenotypes. Pharmacogenet Genomics 23:324–328CrossRefPubMedPubMedCentralGoogle Scholar
  38. Melen E, Himes BE, Brehm JM, Boutaoui N, Klanderman BJ, Sylvia JS, Lasky-Su J (2010) Analyses of shared genetic factors between asthma and obesity in children. J Allergy Clin Immunol 126(631–7):e1–e8PubMedGoogle Scholar
  39. Melen E, Granell R, Kogevinas M, Strachan D, Gonzalez JR, Wjst M, Jarvis D, Ege M, Braun-Fahrlander 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, Celedon JC, Brehm JM, Cloutier MM, Canino G, Acosta-Perez E, Soto-Quiros M, Avila L, Bergstrom A, Magnusson J, Soderhall 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 (2013) Genome-wide association study of body mass index in 23 000 individuals with and without asthma. Clin Exp Allergy 43:463–474CrossRefPubMedPubMedCentralGoogle Scholar
  40. Mohanan S, Tapp H, McWilliams A, Dulin M (2014) Obesity and asthma: pathophysiology and implications for diagnosis and management in primary care. Exp Biol Med (Maywood) 239:1531–1540CrossRefGoogle Scholar
  41. National Center for Biotechnology Information (2009) Database of Genotypes and Phenotypes (dbGAP). National Library of Medicine, BethesdaGoogle Scholar
  42. National Institutes of Health (2015) Precision medicine initiative cohort programGoogle Scholar
  43. Nieminen MM, Kaprio J, Koskenvuo M (1991) A population-based study of bronchial asthma in adult twin pairs. Chest 100:70–75CrossRefPubMedGoogle Scholar
  44. Nishimura KK, Galanter JM, Roth LA, Oh SS, Thakur N, Nguyen EA, Thyne S, Farber HJ, Serebrisky D, Kumar R, Brigino-Buenaventura E, Davis A, LeNoir MA, Meade K, Rodriguez-Cintron W, Avila PC, Borrell LN, Bibbins-Domingo K, Rodriguez-Santana JR, Sen S, Lurmann F, Balmes JR, Burchard EG (2013) Early-life air pollution and asthma risk in minority children. The GALA II and SAGE II studies. Am J Respir Crit Care Med 188:309–318CrossRefPubMedPubMedCentralGoogle Scholar
  45. Ober C, Yao TC (2011) The genetics of asthma and allergic disease: a 21st century perspective. Immunol Rev 242:10–30CrossRefPubMedPubMedCentralGoogle Scholar
  46. Oh SS, White MJ, Gignoux CR, Burchard EG (2016) Making Precision Medicine Socially Precise. Take a Deep Breath. Am J Respir Crit Care Med 193:348–350CrossRefPubMedGoogle Scholar
  47. Pankov Iu A (2013) Major gene mutations associated with obesity and diabetes mellitus. Mol Biol (Mosk) 47:38–49Google Scholar
  48. Parekh N, Guffanti G, Lin Y, Ochs-Balcom HM, Makarem N, Hayes R (2015) Insulin receptor variants and obesity-related cancers in the Framingham Heart Study. Cancer Causes Control 26:1189–1195CrossRefPubMedGoogle Scholar
  49. Pino-Yanes M, Corrales A, Cumplido J, Poza P, Sanchez-Machin I, Sanchez-Palacios A, Figueroa J, Acosta-Fernandez O, Buset N, Garcia-Robaina JC, Hernandez M, Villar J, Carrillo T, Flores C (2013) Assessing the validity of asthma associations for eight candidate genes and age at diagnosis effects. PLoS One 8, e73157CrossRefPubMedPubMedCentralGoogle Scholar
  50. Pino-Yanes M, Thakur N, Gignoux CR, Galanter JM, Roth LA, Eng C, Nishimura KK, Oh SS, Vora H, Huntsman S, Nguyen EA, Hu D, Drake KA, Conti DV, Moreno-Estrada A, Sandoval K, Winkler CA, Borrell LN, Lurmann F, Islam TS, Davis A, Farber HJ, Meade K, Avila PC, Serebrisky D, Bibbins-Domingo K, Lenoir MA, Ford JG, Brigino-Buenaventura E, Rodriguez-Cintron W, Thyne SM, Sen S, Rodriguez-Santana JR, Bustamante CD, Williams LK, Gilliland FD, Gauderman WJ, Kumar R, Torgerson DG, Burchard EG (2015) Genetic ancestry influences asthma susceptibility and lung function among Latinos. J Allergy Clin Immunol 135:228–235CrossRefPubMedGoogle Scholar
  51. Purcell SM, Chang CC (2015) PLINK [Version 1.9]Google Scholar
  52. Schaafsma D, Gosens R, Ris JM, Zaagsma J, Meurs H, Nelemans SA (2007) Insulin induces airway smooth muscle contraction. Br J Pharmacol 150:136–142CrossRefPubMedGoogle Scholar
  53. Sheehan WJ, Phipatanakul W (2015) Difficult-to-control asthma: epidemiology and its link with environmental factors. Curr Opin Allergy Clin Immunol 15:397–401CrossRefPubMedPubMedCentralGoogle Scholar
  54. Shifman S, Kuypers J, Kokoris M, Yakir B, Darvasi A (2003) Linkage disequilibrium patterns of the human genome across populations. Hum Mol Genet 12:771–776CrossRefPubMedGoogle Scholar
  55. Shimizu I, Yoshida Y, Moriya J, Nojima A, Uemura A, Kobayashi Y, Minamino T (2013) Semaphorin3E-induced inflammation contributes to insulin resistance in dietary obesity. Cell Metab 18:491–504CrossRefPubMedGoogle Scholar
  56. Singh S, Prakash YS, Linneberg A, Agrawal A (2013) Insulin and the lung: connecting asthma and metabolic syndrome. J Allergy (Cairo) 2013:627384Google Scholar
  57. Sobota RS, Shriner D, Kodaman N, Goodloe R, Zheng W, Gao YT, Edwards TL, Amos CI, Williams SM (2015) Addressing population-specific multiple testing burdens in genetic association studies. Ann Hum Genet 79:136–147CrossRefPubMedPubMedCentralGoogle Scholar
  58. StataCorp (2011) Stata statistical software: release 12. StataCorp LP, College StationGoogle Scholar
  59. Thakur N, Oh SS, Nguyen EA, Martin M, Roth LA, Galanter J, Gignoux CR, Eng C, Davis A, Meade K, LeNoir MA, Avila PC, Farber HJ, Serebrisky D, Brigino-Buenaventura E, Rodriguez-Cintron W, Kumar R, Williams LK, Bibbins-Domingo K, Thyne S, Sen S, Rodriguez-Santana JR, Borrell LN, Burchard EG (2013) Socioeconomic status and childhood asthma in urban minority youths. The GALA II and SAGE II studies. Am J Respir Crit Care Med 188:1202–1209CrossRefPubMedPubMedCentralGoogle Scholar
  60. Thomsen SF, Ulrik CS, Kyvik KO, Sorensen TI, Posthuma D, Skadhauge LR, Steffensen I, Backer V (2007) Association between obesity and asthma in a twin cohort. Allergy 62:1199–1204CrossRefPubMedGoogle Scholar
  61. Tingley D, Yamamato T, Hirose K, Keele L, Imai K (2014) mediation: R Package for Causal Mediation Analysis. J Stat Softw 59:1–38CrossRefGoogle Scholar
  62. 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, Celedon 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 (2011) Meta-analysis of genome-wide association studies of asthma in ethnically diverse North American populations. Nat Genet 43:887–892CrossRefPubMedPubMedCentralGoogle Scholar
  63. Turner SD (2014) qqman: an R package for visualizing GWAS results using Q-Q and manhattan plots. biorXivGoogle Scholar
  64. Wang D (2000) sg154: confidence intervals for the ratio of two binomial proportions by Koopman’s method. Stata Technical Bulletin, 58 edn. Stata Press, College Station, TXGoogle Scholar
  65. Wang L, Murk W, DeWan AT (2015) Genome-wide gene by environment interaction analysis identifies common SNPs at 17q21.2 that are associated with increased body mass index only among asthmatics. PLoS One 10, e0144114CrossRefPubMedPubMedCentralGoogle Scholar
  66. Ward LD, Kellis M (2012) HaploReg: a resource for exploring chromatin states, conservation, and regulatory motif alterations within sets of genetically linked variants. Nucleic Acids Res 40:D930–D934CrossRefPubMedGoogle Scholar
  67. Welter D, MacArthur J, Morales J, Burdett T, Hall P, Junkins H, Klemm A, Flicek P, Manolio T, Hindorff L, Parkinson H (2014) The NHGRI GWAS Catalog, a curated resource of SNP-trait associations. Nucleic Acids Res 42:D1001–D1006CrossRefPubMedGoogle Scholar
  68. Xu Z, Taylor JA (2009) SNPinfo: integrating GWAS and candidate gene information into functional SNP selection for genetic association studies. Nucleic Acids Res 37:W600–W605CrossRefPubMedPubMedCentralGoogle Scholar
  69. Xu S, Huang W, Wang H, He Y, Wang Y, Wang Y, Qian J, Xiong M, Jin L (2007) Dissecting linkage disequilibrium in African-American genomes: roles of markers and individuals. Mol Biol Evol 24:2049–2058CrossRefPubMedGoogle Scholar
  70. Xu M, Tantisira KG, Wu A, Litonjua AA, Chu JH, Himes BE, Damask A, Weiss ST (2011) Genome Wide Association Study to predict severe asthma exacerbations in children using random forests classifiers. BMC Med Genet 12:90CrossRefPubMedPubMedCentralGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2016

Authors and Affiliations

  • Marquitta J. White
    • 1
  • O. Risse-Adams
    • 1
    • 2
  • P. Goddard
    • 1
  • M. G. Contreras
    • 1
    • 3
  • J. Adams
    • 1
  • D. Hu
    • 1
  • C. Eng
    • 1
  • S. S. Oh
    • 1
  • A. Davis
    • 4
  • K. Meade
    • 4
  • E. Brigino-Buenaventura
    • 5
  • M. A. LeNoir
    • 6
  • K. Bibbins-Domingo
    • 1
  • M. Pino-Yanes
    • 7
    • 8
  • E. G. Burchard
    • 1
    • 9
  1. 1.Department of MedicineUniversity of California, San FranciscoSan FranciscoUSA
  2. 2.Lowell Science Research ProgramLowell High SchoolSan FranciscoUSA
  3. 3.SF BUILDSan Francisco State UniversitySan FranciscoUSA
  4. 4.Children’s Hospital and Research Center OaklandOaklandUSA
  5. 5.Department of Allergy and ImmunologyKaiser Permanente Vallejo Medical CenterVallejoUSA
  6. 6.Bay Area PediatricsOaklandUSA
  7. 7.Research UnitHospital Universitario N.S. de CandelariaTenerifeSpain
  8. 8.CIBER de Enfermedades RespiratoriasInstituto de Salud Carlos IIIMadridSpain
  9. 9.Department of Bioengineering and Therapeutic SciencesUniversity of CaliforniaSan FranciscoUSA

Personalised recommendations