Skip to main content
SpringerLink
Log in

Genome-wide screen for asthma in Puerto Ricans: evidence for association with 5q23 region

  • Original Investigation
  • Published:
Human Genetics Aims and scope Submit manuscript

Abstract

While the number of success stories for mapping genes associated with complex diseases using genome-wide association approaches is growing, there is still much work to be done in developing methods for such studies when the samples are collected from a population, which may not be homogeneous. Here we report the first genome-wide association study to identify genes associated with asthma in an admixed population. We genotyped 96 Puerto Rican moderate to severe asthma cases and 88 controls as well as 109 samples representing Puerto Rico’s founding populations using the Affymetrix GeneChip Human Mapping 100K array sets. The data from samples representing Puerto Rico’s founding populations was used to identify ancestry informative markers for admixture mapping analyses. In addition, a genome-wide association analysis using logistic regression was performed on the data. Although neither admixture mapping nor regression analysis gave any significant association with asthma after correction for multiple testing, an overlap analysis using the top scoring SNPs from different methods suggested chromosomal regions 5q23.3 and 13q13.3 as potential regions harboring genes for asthma in Puerto Ricans. The validation analysis of these two regions in 284 Puerto Rican asthma trios gave significant association for the 5q23.3 region. Our results provide strong evidence that the previously linked 5q23 region is associated with asthma in Puerto Ricans. The detection of causative variants in this region will require fine mapping and functional validation.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5

Similar content being viewed by others

References

  • Bartram U, Speer CP (2004) The role of transforming growth factor beta in lung development and disease. Chest 125:754–765

    Article  PubMed  Google Scholar 

  • Basehore MJ, Howard TD, Lange LA, Moore WC, Hawkins GA, Marshik PL, Harkins MS, Meyers DA, Bleecker ER (2004) A comprehensive evaluation of IL4 variants in ethnically diverse populations: association of total serum IgE levels and asthma in white subjects. J Allergy Clin Immunol 114:80–87

    Article  PubMed  CAS  Google Scholar 

  • Battle N, Choudhry S, Tsai HJ, Eng C, Kumar G, Beckman K, Naqvi M, Meade K, Watson HG, LeNoir M, González Burchard E (2007) Ethnic specific gene–gene interaction between IL-13 and IL4R among African American Asthmatics. Am J Resp Crit Care Med (in press)

  • Benjamini Y, Yekutieli D (2001) The control of the false discovery rate in multiple testing under dependency. Ann Stat 29:1165–1188

    Article  Google Scholar 

  • Buch S, Schafmayer C, Volzke H, Becker C, Franke A, von Eller-Eberstein H, Kluck C, Bassmann I, Brosch M, Lammert F, Miquel JF, Nervi F, Wittig M, Rosskopf D, Timm B, Holl C, Seeger M, ElSharawy A, Lu T, Egberts J, Fandrich F, Folsch UR, Krawczak M, Schreiber S, Nurnberg P, Tepel J, Hampe J (2007) A genome-wide association scan identifies the hepatic cholesterol transporter ABCG8 as a susceptibility factor for human gallstone disease. Nat Genet 39:995–999

    Article  PubMed  CAS  Google Scholar 

  • Burchard EG, Avila PC, Nazario S, Casal J, Torres A, Rodriguez-Santana JR, Toscano M, Sylvia JS, Alioto M, Salazar M, Gomez I, Fagan JK, Salas J, Lilly C, Matallana H, Ziv E, Castro R, Selman M, Chapela R, Sheppard D, Weiss ST, Ford JG, Boushey HA, Rodriguez-Cintron W, Drazen JM, Silverman EK (2004) Lower bronchodilator responsiveness in Puerto Rican than in Mexican subjects with asthma. Am J Respir Crit Care Med 169:386–392

    Article  PubMed  Google Scholar 

  • Burchard EG, Ziv E, Coyle N, Gomez SL, Tang H, Karter AJ, Mountain JL, Perez-Stable EJ, Sheppard D, Risch N (2003) The importance of race and ethnic background in biomedical research and clinical practice. N Engl J Med 348:1170–1175

    Article  PubMed  Google Scholar 

  • Camoretti-Mercado B, Solway J (2005) Transforming growth factor-beta1 and disorders of the lung. Cell Biochem Biophys 43:131–148

    Article  PubMed  CAS  Google Scholar 

  • Cardon LR, Palmer LJ (2003) Population stratification and spurious allelic association. Lancet 361:598–604

    Article  PubMed  Google Scholar 

  • Carter-Pokras OD, Gergen PJ (1993) Reported asthma among Puerto Rican, Mexican-American, and Cuban children, 1982 through 1984. Am J Public Health 83:580–582

    Article  PubMed  CAS  Google Scholar 

  • Chakraborty R, Weiss KM (1988) Admixture as a tool for finding linked genes and detecting that difference from allelic association between loci. Proc Natl Acad Sci USA 85:9119–9123

    Article  PubMed  CAS  Google Scholar 

  • Chen X, Levine L, Kwok PY (1999) Fluorescence polarization in homogeneous nucleic acid analysis. Genome Res 9:492–498

    PubMed  CAS  Google Scholar 

  • Choudhry S, Coyle NE, Tang H, Salari K, Lind D, Clark SL, Tsai HJ, Naqvi M, Phong A, Ung N, Matallana H, Avila PC, Casal J, Torres A, Nazario S, Castro R, Battle NC, Perez-Stable EJ, Kwok PY, Sheppard D, Shriver MD, Rodriguez-Cintron W, Risch N, Ziv E, Burchard EG (2006) Population stratification confounds genetic association studies among Latinos. Hum Genet 118:652–664

    Article  PubMed  Google Scholar 

  • Choudhry S, Seibold MA, Borrell LN, Tang H, Serebrisky D, Chapela R, Rodriguez-Santana JR, Avila PC, Ziv E, Rodriguez-Cintron W, Risch NJ, Burchard EG (2007) Dissecting complex diseases in complex populations: asthma in latino americans. Proc Am Thorac Soc 4:226–233

    Article  PubMed  Google Scholar 

  • Choudhry S, Ung N, Avila PC, Ziv E, Nazario S, Casal J, Torres A, Gorman JD, Salari K, Rodriguez-Santana JR, Toscano M, Sylvia JS, Alioto M, Castro RA, Salazar M, Gomez I, Fagan JK, Salas J, Clark S, Lilly C, Matallana H, Selman M, Chapela R, Sheppard D, Weiss ST, Ford JG, Boushey HA, Drazen JM, Rodriguez-Cintron W, Silverman EK, Burchard EG (2005) Pharmacogenetic differences in response to albuterol between Puerto Ricans and Mexicans with asthma. Am J Respir Crit Care Med 171:563–570

    Article  PubMed  Google Scholar 

  • Colilla S, Nicolae D, Pluzhnikov A, Blumenthal MN, Beaty TH, Bleecker ER, Lange EM, Rich SS, Meyers DA, Ober C, Cox NJ (2003) Evidence for gene-environment interactions in a linkage study of asthma and smoking exposure. J Allergy Clin Immunol 111:840–846

    Article  PubMed  Google Scholar 

  • Devlin B, Roeder K (1999) Genomic control for association studies. Biometrics 55:997–1004

    Article  PubMed  CAS  Google Scholar 

  • Falush D, Stephens M, Pritchard JK (2003) Inference of population structure using multilocus genotype data: linked loci and correlated allele frequencies. Genetics 164:1567–1587

    PubMed  CAS  Google Scholar 

  • Gudmundsson J, Sulem P, Manolescu A, Amundadottir LT, Gudbjartsson D, Helgason A, Rafnar T, Bergthorsson JT, Agnarsson BA, Baker A, Sigurdsson A, Benediktsdottir KR, Jakobsdottir M, Xu J, Blondal T, Kostic J, Sun J, Ghosh S, Stacey SN, Mouy M, Saemundsdottir J, Backman VM, Kristjansson K, Tres A, Partin AW, Albers-Akkers MT, Godino-Ivan Marcos J, Walsh PC, Swinkels DW, Navarrete S, Isaacs SD, Aben KK, Graif T, Cashy J, Ruiz-Echarri M, Wiley KE, Suarez BK, Witjes JA, Frigge M, Ober C, Jonsson E, Einarsson GV, Mayordomo JI, Kiemeney LA, Isaacs WB, Catalona WJ, Barkardottir RB, Gulcher JR, Thorsteinsdottir U, Kong A, Stefansson K (2007) Genome-wide association study identifies a second prostate cancer susceptibility variant at 8q24. Nat Genet 39:631–637

    Article  PubMed  CAS  Google Scholar 

  • Haagerup A, Borglum AD, Binderup HG, Kruse TA (2004) Fine-scale mapping of type I allergy candidate loci suggests central susceptibility genes on chromosomes 3q, 4q and Xp. Allergy 59:88–94

    Article  PubMed  CAS  Google Scholar 

  • Hafler DA, Compston A, Sawcer S, Lander ES, Daly MJ, De Jager PL, de Bakker PI, Gabriel SB, Mirel DB, Ivinson AJ, Pericak-Vance MA, Gregory SG, Rioux JD, McCauley JL, Haines JL, Barcellos LF, Cree B, Oksenberg JR, Hauser SL (2007) Risk alleles for multiple sclerosis identified by a genomewide study. N Engl J Med 357:851–862

    Article  PubMed  CAS  Google Scholar 

  • Hakonarson H, Grant SF, Bradfield JP, Marchand L, Kim CE, Glessner JT, Grabs R, Casalunovo T, Taback SP, Frackelton EC, Lawson ML, Robinson LJ, Skraban R, Lu Y, Chiavacci RM, Stanley CA, Kirsch SE, Rappaport EF, Orange JS, Monos DS, Devoto M, Qu HQ, Polychronakos C (2007) A genome-wide association study identifies KIAA0350 as a type 1 diabetes gene. Nature 448:591–594

    Article  PubMed  CAS  Google Scholar 

  • Hanis CL, Hewett-Emmett D, Bertin TK, Schull WJ (1991) Origins of U.S. Hispanics. Implications for diabetes. Diabetes Care 14:618–627

    Article  PubMed  CAS  Google Scholar 

  • Hinds DA, Stuve LL, Nilsen GB, Halperin E, Eskin E, Ballinger DG, Frazer KA, Cox DR (2005) Whole-genome patterns of common DNA variation in three human populations. Science 307:1072–1079

    Article  PubMed  CAS  Google Scholar 

  • Hirschhorn JN, Daly MJ (2005) Genome-wide association studies for common diseases and complex traits. Nat Rev Genet 6:95–108

    Article  PubMed  CAS  Google Scholar 

  • Hoffjan S, Ober C (2002) Present status on the genetic studies of asthma. Curr Opin Immunol 14:709–717

    Article  PubMed  CAS  Google Scholar 

  • Hoggart CJ, Parra EJ, Shriver MD, Bonilla C, Kittles RA, Clayton DG, McKeigue PM (2003) Control of confounding of genetic associations in stratified populations. Am J Hum Genet 72:1492–1504

    Article  PubMed  CAS  Google Scholar 

  • Hoggart CJ, Shriver MD, Kittles RA, Clayton DG, McKeigue PM (2004) Design and analysis of admixture mapping studies. Am J Hum Genet 74:965–978

    Article  PubMed  CAS  Google Scholar 

  • Homa DM, Mannino DM, Lara M (2000) Asthma mortality in U.S. Hispanics of Mexican, Puerto Rican, and Cuban heritage, 1990–1995. Am J Respir Crit Care Med 161:504–509

    PubMed  CAS  Google Scholar 

  • Howard TD, Koppelman GH, Xu J, Zheng SL, Postma DS, Meyers DA, Bleecker ER (2002) Gene-gene interaction in asthma: IL4RA and IL13 in a Dutch population with asthma. Am J Hum Genet 70:230–206

    Article  PubMed  CAS  Google Scholar 

  • Huang SK, Mathias RA, Ehrlich E, Plunkett B, Liu X, Cutting GR, Wang XJ, Li XD, Togias A, Barnes KC, Malveaux F, Rich S, Mellen B, Lange E, Beaty TH, Asthma CSotGo (2003) Evidence for asthma susceptibility genes on chromosome 11 in an African-American population. Hum Genet 113:71–75

    Article  PubMed  CAS  Google Scholar 

  • Kennedy GC, Matsuzaki H, Dong S, Liu WM, Huang J, Liu G, Su X, Cao M, Chen W, Zhang J, Liu W, Yang G, Di X, Ryder T, He Z, Surti U, Phillips MS, Boyce-Jacino MT, Fodor SP, Jones KW (2003) Large-scale genotyping of complex DNA. Nat Biotechnol 21:1233–1237

    Article  PubMed  CAS  Google Scholar 

  • Koppelman GH, Stine OC, Xu J, Howard TD, Zheng SL, Kauffman HF, Bleecker ER, Meyers DA, Postma DS (2002) Genome-wide search for atopy susceptibility genes in Dutch families with asthma. J Allergy Clin Immunol 109:498–506

    Article  PubMed  CAS  Google Scholar 

  • Laird NM, Horvath S, Xu X (2000) Implementing a unified approach to family-based tests of association. Genet Epidemiol 19 Suppl 1: S36–S42

    Article  Google Scholar 

  • Li H, Romieu I, Wu H, Sienra-Monge JJ, Ramirez-Aguilar M, Del Rio-Navarro BE, Del Lara-Sanchez IC, Kistner EO, Gjessing HK, London SJ (2007) Genetic polymorphisms in transforming growth factor beta-1 (TGFB1) and childhood asthma and atopy. Hum Genet (in press)

  • Lind DL, Choudhry S, Ung N, Ziv E, Avila PC, Salari K, Ha C, Lovins EG, Coyle NE, Nazario S, Casal J, Torres A, Rodriguez-Santana JR, Matallana H, Lilly CM, Salas J, Selman M, Boushey HA, Weiss ST, Chapela R, Ford JG, Rodriguez-Cintron W, Silverman EK, Sheppard D, Kwok PY, Gonzalez Burchard E (2003) ADAM33 is not associated with asthma in Puerto Rican or Mexican populations. Am J Respir Crit Care Med 168:1312–1316

    Article  PubMed  Google Scholar 

  • Mao X, Bigham AW, Mei R, Gutierrez G, Weiss KM, Brutsaert TD, Leon-Velarde F, Moore LG, Vargas E, McKeigue PM, Shriver MD, Parra EJ (2007) A genomewide admixture mapping panel for Hispanic/Latino populations. Am J Hum Genet 80:1171–1178

    Article  PubMed  CAS  Google Scholar 

  • Marchini J, Cardon LR, Phillips MS, Donnelly P (2004) The effects of human population structure on large genetic association studies. Nat Genet 36:512–517

    Article  PubMed  CAS  Google Scholar 

  • Marsh DG, Neely JD, Breazeale DR, Ghosh B, Freidhoff LR, Ehrlich-Kautzky E, Schou C, Krishnaswamy G, Beaty TH (1994) Linkage analysis of IL4 and other chromosome 5q31.1 markers and total serum immunoglobulin E concentrations. Science 264:1152–1156

    Article  PubMed  CAS  Google Scholar 

  • Mathias RA, Gao P, Goldstein JL, Wilson AF, Pugh EW, Furbert-Harris P, Dunston GM, Malveaux FJ, Togias A, Barnes KC, Beaty TH, Huang SK (2006) A graphical assessment of p-values from sliding window haplotype tests of association to identify asthma susceptibility loci on chromosome 11q. BMC Genet 7:38

    Article  PubMed  CAS  Google Scholar 

  • Matsuzaki H, Dong S, Loi H, Di X, Liu G, Hubbell E, Law J, Berntsen T, Chadha M, Hui H, Yang G, Kennedy GC, Webster TA, Cawley S, Walsh PS, Jones KW, Fodor SP, Mei R (2004) Genotyping over 100,000 SNPs on a pair of oligonucleotide arrays. Nat Methods 1:109–111

    Article  PubMed  CAS  Google Scholar 

  • McKeigue PM (1997) Mapping genes underlying ethnic differences in disease risk by linkage disequilibrium in recently admixed populations. Am J Hum Genet 60:188–196

    PubMed  CAS  Google Scholar 

  • McKeigue PM (1998) Mapping genes that underlie ethnic differences in disease risk: methods for detecting linkage in admixed populations, by conditioning on parental admixture. Am J Hum Genet 63:241–251

    Article  PubMed  CAS  Google Scholar 

  • McPherson R, Pertsemlidis A, Kavaslar N, Stewart A, Roberts R, Cox DR, Hinds DA, Pennacchio LA, Tybjaerg-Hansen A, Folsom AR, Boerwinkle E, Hobbs HH, Cohen JC (2007) A common allele on chromosome 9 associated with coronary heart disease. Science 316:1488–1491

    Article  PubMed  CAS  Google Scholar 

  • Moffatt MF, Kabesch M, Liang L, Dixon AL, Strachan D, Heath S, Depner M, von Berg A, Bufe A, Rietschel E, Heinzmann A, Simma B, Frischer T, Willis-Owen SA, Wong KC, Illig T, Vogelberg C, Weiland SK, von Mutius E, Abecasis GR, Farrall M, Gut IG, Lathrop GM, Cookson WO (2007) Genetic variants regulating ORMDL3 expression contribute to the risk of childhood asthma. Nature 448:470–473

    Article  PubMed  CAS  Google Scholar 

  • Montana G, Pritchard JK (2004) Statistical tests for admixture mapping with case-control and cases-only data. Am J Hum Genet 75:771–789

    Article  PubMed  CAS  Google Scholar 

  • Ober C, Cox NJ, Abney M, Di Rienzo A, Lander ES, Changyaleket B, Gidley H, Kurtz B, Lee J, Nance M, Pettersson A, Prescott J, Richardson A, Schlenker E, Summerhill E, Willadsen S, Parry R (1998) Genome-wide search for asthma susceptibility loci in a founder population. The Collaborative Study on the Genetics of Asthma. Hum Mol Genet 7:1393–1398

    Article  PubMed  CAS  Google Scholar 

  • Ober C, Tsalenko A, Parry R, Cox NJ (2000) A second-generation genomewide screen for asthma-susceptibility alleles in a founder population. Am J Hum Genet 67:1154–1162

    PubMed  CAS  Google Scholar 

  • Pfaff CL, Parra EJ, Bonilla C, Hiester K, McKeigue PM, Kamboh MI, Hutchinson RG, Ferrell RE, Boerwinkle E, Shriver MD (2001) Population structure in admixed populations: effect of admixture dynamics on the pattern of linkage disequilibrium. Am J Hum Genet 68:198–207

    Article  PubMed  CAS  Google Scholar 

  • Pillai SG, Chiano MN, White NJ, Speer M, Barnes KC, Carlsen K, Gerritsen J, Helms P, Lenney W, Silverman M, Sly P, Sundy J, Tsanakas J, von Berg A, Whyte M, Varsani S, Skelding P, Hauser M, Vance J, Pericak-Vance M, Burns DK, Middleton LT, Brewster SR, Anderson WH, Riley JH (2006) A genome-wide search for linkage to asthma phenotypes in the genetics of asthma international network families: evidence for a major susceptibility locus on chromosome 2p. Eur J Hum Genet 14:307–316

    Article  PubMed  CAS  Google Scholar 

  • Postma DS, Meyers DA, Jongepier H, Howard TD, Koppelman GH, Bleecker ER (2005) Genomewide screen for pulmonary function in 200 families ascertained for asthma. Am J Respir Crit Care Med 172:446–452

    Article  PubMed  Google Scholar 

  • Price AL, Patterson N, Yu F, Cox DR, Waliszewska A, McDonald GJ, Tandon A, Schirmer C, Neubauer J, Bedoya G, Duque C, Villegas A, Bortolini MC, Salzano FM, Gallo C, Mazzotti G, Tello-Ruiz M, Riba L, Aguilar-Salinas CA, Canizales-Quinteros S, Menjivar M, Klitz W, Henderson B, Haiman CA, Winkler C, Tusie-Luna T, Ruiz-Linares A, Reich D (2007) A genomewide admixture map for Latino populations. Am J Hum Genet 80:1024–1036

    Article  PubMed  CAS  Google Scholar 

  • Pritchard JK, Stephens M, Donnelly P (2000) Inference of population structure using multilocus genotype data. Genetics 155:945–959

    PubMed  CAS  Google Scholar 

  • Risch NJ (2000) Searching for genetic determinants in the new millennium. Nature 405:847–856

    Article  PubMed  CAS  Google Scholar 

  • Samani NJ, Erdmann J, Hall AS, Hengstenberg C, Mangino M, Mayer B, Dixon RJ, Meitinger T, Braund P, Wichmann HE, Barrett JH, Konig IR, Stevens SE, Szymczak S, Tregouet DA, Iles MM, Pahlke F, Pollard H, Lieb W, Cambien F, Fischer M, Ouwehand W, Blankenberg S, Balmforth AJ, Baessler A, Ball SG, Strom TM, Braenne I, Gieger C, Deloukas P, Tobin MD, Ziegler A, Thompson JR, Schunkert H (2007) Genomewide association analysis of coronary artery disease. N Engl J Med 357:443–453

    Article  PubMed  CAS  Google Scholar 

  • Saxena R, Voight BF, Lyssenko V, Burtt NP, de Bakker PI, Chen H, Roix JJ, Kathiresan S, Hirschhorn JN, Daly MJ, Hughes TE, Groop L, Altshuler D, Almgren P, Florez JC, Meyer J, Ardlie K, Bengtsson Bostrom K, Isomaa B, Lettre G, Lindblad U, Lyon HN, Melander O, Newton-Cheh C, Nilsson P, Orho-Melander M, Rastam L, Speliotes EK, Taskinen MR, Tuomi T, Guiducci C, Berglund A, Carlson J, Gianniny L, Hackett R, Hall L, Holmkvist J, Laurila E, Sjogren M, Sterner M, Surti A, Svensson M, Tewhey R, Blumenstiel B, Parkin M, Defelice M, Barry R, Brodeur W, Camarata J, Chia N, Fava M, Gibbons J, Handsaker B, Healy C, Nguyen K, Gates C, Sougnez C, Gage D, Nizzari M, Gabriel SB, Chirn GW, Ma Q, Parikh H, Richardson D, Ricke D, Purcell S (2007) Genome-wide association analysis identifies loci for type 2 diabetes and triglyceride levels. Science 316:1331–1336

    Article  PubMed  CAS  Google Scholar 

  • Scott LJ, Mohlke KL, Bonnycastle LL, Willer CJ, Li Y, Duren WL, Erdos MR, Stringham HM, Chines PS, Jackson AU, Prokunina-Olsson L, Ding CJ, Swift AJ, Narisu N, Hu T, Pruim R, Xiao R, Li XY, Conneely KN, Riebow NL, Sprau AG, Tong M, White PP, Hetrick KN, Barnhart MW, Bark CW, Goldstein JL, Watkins L, Xiang F, Saramies J, Buchanan TA, Watanabe RM, Valle TT, Kinnunen L, Abecasis GR, Pugh EW, Doheny KF, Bergman RN, Tuomilehto J, Collins FS, Boehnke M (2007) A genome-wide association study of type 2 diabetes in Finns detects multiple susceptibility variants. Science 316:1341–1345

    Article  PubMed  CAS  Google Scholar 

  • Smith MW, O’Brien SJ (2005) Mapping by admixture linkage disequilibrium: advances, limitations and guidelines. Nat Rev Genet 6:623–632

    Article  PubMed  CAS  Google Scholar 

  • Smith MW, Patterson N, Lautenberger JA, Truelove AL, McDonald GJ, Waliszewska A, Kessing BD, Malasky MJ, Scafe C, Le E, De Jager PL, Mignault AA, Yi Z, De The G, Essex M, Sankale JL, Moore JH, Poku K, Phair JP, Goedert JJ, Vlahov D, Williams SM, Tishkoff SA, Winkler CA, De La Vega FM, Woodage T, Sninsky JJ, Hafler DA, Altshuler D, Gilbert DA, O’Brien SJ, Reich D (2004) A high-density admixture map for disease gene discovery in african americans. Am J Hum Genet 74:1001–1013

    Article  PubMed  CAS  Google Scholar 

  • Steinthorsdottir V, Thorleifsson G, Reynisdottir I, Benediktsson R, Jonsdottir T, Walters GB, Styrkarsdottir U, Gretarsdottir S, Emilsson V, Ghosh S, Baker A, Snorradottir S, Bjarnason H, Ng MC, Hansen T, Bagger Y, Wilensky RL, Reilly MP, Adeyemo A, Chen Y, Zhou J, Gudnason V, Chen G, Huang H, Lashley K, Doumatey A, So WY, Ma RC, Andersen G, Borch-Johnsen K, Jorgensen T, van Vliet-Ostaptchouk JV, Hofker MH, Wijmenga C, Christiansen C, Rader DJ, Rotimi C, Gurney M, Chan JC, Pedersen O, Sigurdsson G, Gulcher JR, Thorsteinsdottir U, Kong A, Stefansson K (2007) A variant in CDKAL1 influences insulin response and risk of type 2 diabetes. Nat Genet 39:770–775

    Article  PubMed  CAS  Google Scholar 

  • Stephens JC, Briscoe D, O’Brien SJ (1994) Mapping by admixture linkage disequilibrium in human populations: limits and guidelines. Am J Hum Genet 55:809–824

    PubMed  CAS  Google Scholar 

  • Terwilliger JD, Weiss KM (1998) Linkage disequilibrium mapping of complex disease: fantasy or reality? Curr Opin Biotechnol 9:578–594

    Article  PubMed  CAS  Google Scholar 

  • Tian C, Hinds DA, Shigeta R, Adler SG, Lee A, Pahl MV, Silva G, Belmont JW, Hanson RL, Knowler WC, Gregersen PK, Ballinger DG, Seldin MF (2007) A genomewide single-nucleotide-polymorphism panel for Mexican American admixture mapping. Am J Hum Genet 80:1014–1023

    Article  PubMed  CAS  Google Scholar 

  • Tomlinson I, Webb E, Carvajal-Carmona L, Broderick P, Kemp Z, Spain S, Penegar S, Chandler I, Gorman M, Wood W, Barclay E, Lubbe S, Martin L, Sellick G, Jaeger E, Hubner R, Wild R, Rowan A, Fielding S, Howarth K, Silver A, Atkin W, Muir K, Logan R, Kerr D, Johnstone E, Sieber O, Gray R, Thomas H, Peto J, Cazier JB, Houlston R (2007) A genome-wide association scan of tag SNPs identifies a susceptibility variant for colorectal cancer at 8q24.21. Nat Genet 39:984–988

    Article  PubMed  CAS  Google Scholar 

  • Wellcome Trust Care Control Consortium (WTCCC) (2007) Genome-wide association study of 14,000 cases of seven common diseases and 3,000 shared controls. Nature 447:661–678

    Article  CAS  Google Scholar 

  • Wiltshire S, Bhattacharyya S, Faux JA, Leaves NI, Daniels SE, Moffatt MF, James A, Musk AW, Cookson WO (1998) A genome scan for loci influencing total serum immunoglobulin levels: possible linkage of IgA to the chromosome 13 atopy locus. Hum Mol Genet 7:27–31

    Article  PubMed  CAS  Google Scholar 

  • Winkelmann J, Schormair B, Lichtner P, Ripke S, Xiong L, Jalilzadeh S, Fulda S, Putz B, Eckstein G, Hauk S, Trenkwalder C, Zimprich A, Stiasny-Kolster K, Oertel W, Bachmann CG, Paulus W, Peglau I, Eisensehr I, Montplaisir J, Turecki G, Rouleau G, Gieger C, Illig T, Wichmann HE, Holsboer F, Muller-Myhsok B, Meitinger T (2007) Genome-wide association study of restless legs syndrome identifies common variants in three genomic regions. Nat Genet 39:1000–1006

    Article  PubMed  CAS  Google Scholar 

  • Xu J, Postma DS, Howard TD, Koppelman GH, Zheng SL, Stine OC, Bleecker ER, Meyers DA (2000) Major genes regulating total serum immunoglobulin E levels in families with asthma. Am J Hum Genet 67:1163–1173

    Article  PubMed  CAS  Google Scholar 

  • Yeager M, Orr N, Hayes RB, Jacobs KB, Kraft P, Wacholder S, Minichiello MJ, Fearnhead P, Yu K, Chatterjee N, Wang Z, Welch R, Staats BJ, Calle EE, Feigelson HS, Thun MJ, Rodriguez C, Albanes D, Virtamo J, Weinstein S, Schumacher FR, Giovannucci E, Willett WC, Cancel-Tassin G, Cussenot O, Valeri A, Andriole GL, Gelmann EP, Tucker M, Gerhard DS, Fraumeni JF Jr, Hoover R, Hunter DJ, Chanock SJ, Thomas G (2007) Genome-wide association study of prostate cancer identifies a second risk locus at 8q24. Nat Genet 39:645–649

    Article  PubMed  CAS  Google Scholar 

  • Zanke BW, Greenwood CM, Rangrej J, Kustra R, Tenesa A, Farrington SM, Prendergast J, Olschwang S, Chiang T, Crowdy E, Ferretti V, Laflamme P, Sundararajan S, Roumy S, Olivier JF, Robidoux F, Sladek R, Montpetit A, Campbell P, Bezieau S, O’Shea AM, Zogopoulos G, Cotterchio M, Newcomb P, McLaughlin J, Younghusband B, Green R, Green J, Porteous ME, Campbell H, Blanche H, Sahbatou M, Tubacher E, Bonaiti-Pellie C, Buecher B, Riboli E, Kury S, Chanock SJ, Potter J, Thomas G, Gallinger S, Hudson TJ, Dunlop MG (2007) Genome-wide association scan identifies a colorectal cancer susceptibility locus on chromosome 8q24. Nat Genet 39:989–994

    Article  PubMed  CAS  Google Scholar 

  • Zeggini E, Weedon MN, Lindgren CM, Frayling TM, Elliott KS, Lango H, Timpson NJ, Perry JR, Rayner NW, Freathy RM, Barrett JC, Shields B, Morris AP, Ellard S, Groves CJ, Harries LW, Marchini JL, Owen KR, Knight B, Cardon LR, Walker M, Hitman GA, Morris AD, Doney AS, McCarthy MI, Hattersley AT (2007) Replication of genome-wide association signals in UK samples reveals risk loci for type 2 diabetes. Science 316:1336–1341

    Article  PubMed  CAS  Google Scholar 

  • Ziv E, Burchard EG (2003) Human population structure and genetic association studies. Pharmacogenomics 4:431–441

    Article  PubMed  Google Scholar 

Download references

Acknowledgments

The authors would like to acknowledge the families and the patients for their participation. We would also like to thank the numerous health care providers and community clinics for their support and participation in the GALA Study. Finally, we would like to especially thank Jeffrey M. Drazen, M.D., Scott Weiss, M.D., Ed Silverman, M.D., Ph.D., Homer A. Boushey, M.D., Jean G. Ford, M.D. and Dean Sheppard, M.D. for all of their effort towards the creation of the GALA Study. This work was supported by National Institutes of Health (HL078885), RWJ Amos Medical Faculty Development Award, NCMHD Health Disparities Scholar, Extramural Clinical Research, Loan Repayment Program for Individuals from Disadvantaged Backgrounds, 2001–2003, to EGB), American Thoracic Society “Breakthrough Opportunities in Lung Disease” (BOLD) Award and Tobacco-Related Disease Research Program New Investigator Award (15KT-0008) to SC, and the Sandler Center for Basic Research in Asthma, the Sandler Family Supporting Foundation and the Flight Attendant Medical Research Institute (FAMRI).

Author information

Authors and Affiliations

  1. Institute for Human Genetics, University of California, San Francisco, CA, USA

    Shweta Choudhry, Elad Ziv, Neil J. Risch & Esteban González Burchard

  2. UCSF/Lung Biology Center, University of California, San Francisco, San Francisco, CA, 94158-2911, USA

    Shweta Choudhry & Esteban González Burchard

  3. Department of Medicine, University of California, San Francisco, CA, USA

    Shweta Choudhry, Elad Ziv & Esteban González Burchard

  4. Department of Biopharmaceutical Sciences, University of California, San Francisco, CA, USA

    Esteban González Burchard

  5. Department of Epidemiology and Biostatistics, University of California, San Francisco, CA, USA

    Neil J. Risch

  6. Department of Biostatistics, University of California, Berkeley, CA, USA

    Margaret Taub

  7. Affymetrix Inc, Santa Clara, CA, USA

    Rui Mei

  8. Centro de Neumologia Pediatrica, CSP, San Juan, PR, USA

    José Rodriguez-Santana

  9. Veterans Caribbean Health Care System, The University of Puerto Rico School of Medicine, San Juan, PR, USA

    William Rodriguez-Cintron

  10. Department of Anthropology, Pennsylvania State University, University Park, PA, USA

    Mark D. Shriver

  11. Division of Research, Kaiser Permanente, Oakland, CA, USA

    Neil J. Risch & Esteban González Burchard

Authors
  1. Shweta Choudhry
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Margaret Taub
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Rui Mei
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. José Rodriguez-Santana
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. William Rodriguez-Cintron
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Mark D. Shriver
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Elad Ziv
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Neil J. Risch
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Esteban González Burchard
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Shweta Choudhry.

Additional information

S. Choudhry and M. Taub contributed equally to the manuscript.

Electronic supplementary material

Below is the link to the electronic supplementary material.

Supporting material (XLS 686 kb)

Rights and permissions

Reprints and permissions

About this article

Cite this article

Choudhry, S., Taub, M., Mei, R. et al. Genome-wide screen for asthma in Puerto Ricans: evidence for association with 5q23 region. Hum Genet 123, 455–468 (2008). https://doi.org/10.1007/s00439-008-0495-7

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00439-008-0495-7

Keywords

Search

Navigation