Skip Navigation
 

Genetics, Environment & Respiratory Disease Group

Genetic Susceptibility & the Environment

Stephanie J. London, M.D., Dr.P.H.
Stephanie J. London, M.D., Dr.P.H.
Principal Investigator
Tel (919) 541-5772
Fax (919) 541-2511
london2@niehs.nih.gov
Curriculum Vitae (http://www.niehs.nih.gov/businesscards/docs/london_stephanie_j.pdf) (370KB)
P.O. Box 12233
Mail Drop A3-05
Research Triangle Park, North Carolina 27709
Delivery Instructions


Research Summary

The Genetics, Environment & Respiratory Disease Group, headed by Stephanie J. London, M.D, Dr.P.H., focuses on genetic susceptibility and interactions between genetics and the environment in relation to respiratory endpoints, including asthma, pulmonary function and chronic obstructive pulmonary disease.

 

London began work on genetic susceptibility to respiratory disease in 1990 with a study of lung cancer. This population-based case-control study of African-Americans and Caucasians in Los Angeles County investigated candidate genes. Later, working with her collaborators in a cohort of Shanghai men, she reported the first example of a gene-diet interaction based on a dietary biomarker. She found that the protective effect of higher intake of isothiocyanates, a chemopreventive substance in Brassica vegetables, was predominantly seen among individuals with genetically impaired ability to eliminate these compounds (GSTM1 null genotype). This finding has been widely replicated.

 

London now focuses on environmental causes, genetic susceptibility and interactions in relation to nonmalignant respiratory conditions. In the early 1990s, she was part of the small group of investigators at the University of Southern California who established the landmark Children's Health Study, a school-based cohort study of health effects of air pollution among Southern California children. After coming to NIEHS in 1995, she established the genetic component of this study, collecting buccal cells from the children to examine candidate gene polymorphisms. This addition to the study was so successful that it subsequently became the basis for extensive extramural funding for the investigators who replaced her at USC.

 

London established a collaboration to study the role of diet, genetics and the environment in relation to asthma and chronic bronchitis in a cohort of adults of Chinese ethnicity in Singapore. She added assessment and validation of respiratory outcomes to this study. These data have shown a protective effect of dietary fiber on the development of chronic bronchitis symptoms. She and her collaborators corroborated these findings in relation to pulmonary function in the Atherosclerosis Risk in Communities (ARIC) Study. To better understand the complex interplay between correlated intakes of foods and nutrients, London and colleagues studied dietary patterns in relation to chronic bronchitis symptoms in the Singapore study. This work indicated that independent of fiber intake, high intake of a diet high in fresh and preserved red meat, refined carbohydrates, and sodium was associated with increased risk. This was the first examination of dietary patterns in relation to nonmalignant respiratory disease.

 

London established a collaboration with investigators in Norway to study early life factors in relation to asthma and allergies within the Norwegian Mother and Child (MoBa) pregnancy cohort. One of the notable findings of the MoBa asthma group has been an increased risk of early asthma phenotypes in relation to maternal folate levels. London and her colleagues are now following up this finding with a study of genome wide methylation (Illumina 450K) to investigate possible epigenetic mechanisms. London received funding to follow the MoBa cohort at age seven by questionnaire to identify asthma and allergies at an age when they can be more reliably ascertained. This follow-up is ongoing.

 

London worked with Jane Hoppin, Sc.D., at NIEHS to establish a nested case-control study of adult asthma within the Agricultural Health Study (AHS), a cohort of license pesticide applicators, mostly farmers, and their spouses. The study is designed to follow-up questionnaire-based findings from the AHS indicating that exposure to pesticides, especially organophosphates, are related to wheezing phenotypes. The study will also investigate exposure to pathogen associated molecules (PAMPs), such as endotoxin and glucans and peptidoglyan, in relation to asthma. Another goal is to study gene by environment interactions. The study staff are enrolling cases and controls in their homes and measuring pulmonary function, bronchodilator response, exhaled nitric oxide and collecting blood for measurements of atopic status and genetic analyses. Dust samples are collected for measurements of PAMPs. The study is ongoing with over 1,300 subjects enrolled.

 

In the past several years, London’s genetic work has shifted from candidate gene to genome-wide association studies (GWAS). She published a GWAS of asthma within her case-parent triad study of childhood asthma in Mexico City (MCCAS). The study is now part of the EVE consortium of NIH-funded asthma GWASes. She has also collaborated with the Atherosclerosis Risk in Communities Study and the larger CHARGE consortium to do GWASes of pulmonary function and related phenotypes in adults. This work lead to the discovery of a number of novel loci related to pulmonary function. She leads the CHARGE pulmonary group which continues to analyze this rich GWAS dataset in collaboration with the SpiroMeta consortium in the UK and other European collaborators.

 

London earned a B.A. from Harvard College, an M.D. and an M.P.H in occupational health from Harvard Medical School, and a Dr.P.H. in epidemiology from the Harvard School of Public Health. She is licensed in California, and is Board Certified in Internal Medicine and Preventive Medicine, with Specialty in Occupational and Environmental Medicine. London was Assistant Professor, Department of Preventive Medicine at the University of Southern California School of Medicine, Los Angeles, before coming to NIEHS in 1995. She is currently a Principal Investigator at NIEHS and holds a dual appointment in the Laboratory of Respiratory Biology.

Studies

  • CHARGE Consortium Pulmonary Group

  • LA Lung Study
    The LA Lung study was one of the first studies of genetic susceptibility to lung cancer using population controls and including large numbers of African-Americans. Recently, the study has been included in a number of pooled analyses from the Collaborative Studies on the Genetics of Cancer.

  • Mexico Childhood Asthma Study
    The Mexico Childhood Asthma Study is a case-parent triad study of childhood allergic asthma in Mexico City. This study is now part of the EVE consortium of NIH-funded asthma GWAS.

  • Norwegian Mother and Child Cohort Study (MoBa)

  • OBOZ Study
     The OBOZ Study will investigate whether obesity affects respiratory response to ozone. It is a collaborative effort between London’s and investigators from the Center for Environmental Medicine and Lung Biology (CEMALB) at the University of North Carolina at Chapel Hill.

  • Shanghai Study

  • Singapore Chinese Health Study
     The Singapore Chinese Health Study examines the environmental, dietary and genetic risk factors for respiratory disease.

  • Wuhan Study


Back to top Back to top

Selected Publications

  1. London SJ, Yuan J-M, Chung FL, Gao YT, Coetzee GA, Yu MC, Ross RK. Isothiocyanates, glutathione S-transferase M1 and T1 polymorphisms and lung cancer risk: a prospective study of men in Shanghai, China. Lancet. 356:724-729, 2000. [Abstract (http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=AbstractPlus&list_uids=11085692&query_hl=4&itool=pubmed_docsum) ]
  2. London SJ, Gauderman WJ, Avol E, Rappaport E, Peters JM. Family history and the risk of early onset persistent, early onset transient and late onset asthma. Epidemiology. 12:577-583, 2001. [Abstract (http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=AbstractPlus&list_uids=11505179&query_hl=1&itool=pubmed_docsum) ]
  3. London SJ, Yuan J-M, Travlos G, Gao Y-T, Wilson R, Ross RK, Yu MC. Insulin-like growth factor 1, IGF-binding protein 3, and lung cancer risk in a prospective study of men in China. J. Natl Cancer Inst. 15:749-754, 2002. [Abstract (http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=AbstractPlus&list_uids=12011225&query_hl=4&itool=pubmed_docsum) ]
  4. David GL, Romieu I, Sienra-Monge JJ, Collins WJ, Ramirez-Aguilar M, del Rio-Navarro BE, Reyes-Ruiz NI, Morris R, Marzec JM, London SJ. Nicotinamide adenine dinucleotide (phosphate) reduced:quinone oxidoreductase and glutathione S-transferase M1 polymorphisms and childhood asthma. Am J Respir Crit Care Med. 168:1199-1204, 2003. [Abstract (http://www.ncbi.nlm.nih.gov/pubmed/12969868) ] [Full Text (http://ajrccm.atsjournals.org/cgi/content/full/168/10/1199) ] [download the PDF (http://ajrccm.atsjournals.org/cgi/reprint/168/10/1199) ]
  5. Romieu I, Sienra-Monge JJ, Ramirez M, Moreno-Macias H, Reyes-Ruiz NI, del Rio-Navarro BE, Hernandez-Avila M, London SJ. Genetic polymorphism of GSTM1 and antioxidant supplementation influence lung function in relation to ozone exposure among Mexico City children. Thorax. 59:8-10, 2004. [Abstract (http://www.ncbi.nlm.nih.gov/pubmed/14694237) ] [Full Text (http://thorax.bmj.com/content/59/1/8.full) ] [download the PDF (http://thorax.bmjjournals.com/cgi/reprint/59/1/8) ]
  6. Butler LM, Koh WP, Lee HP, Yu MC, London SJ. Dietary fiber and reduced cough with phlegm: a cohort study in Singapore. Am J Respir Crit Care Med. 170:279-287, 2004. [Abstract (http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=15117740) ] [Full Text (http://ajrccm.atsjournals.org/cgi/content/full/170/3/279) ] [download the PDF (http://ajrccm.atsjournals.org/cgi/reprint/170/3/279) ]
  7. David GL, Koh W-P, Lee H-P, Yu MC, London SJ. Childhood exposure to environmental tobacco smoke and chronic respiratory symptoms in nonsmoking adults: Singapore Chinese Health Study. Thorax. 60:1052-1058, 2005. Epub Aug 30, 2005. [Abstract (http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=AbstractPlus&list_uids=16131525&query_hl=10&itool=pubmed_docsum) ]
  8. Butler LM, Koh W-P, Lee H-P, Tseng M, Yu MC, London SJ. Prospective study of dietary patterns and persistent cough with phlegm among Chinese Singaporeans. Am J Respir Crit Care Med. 173:264-270, 2006. Epub Oct 20, 2005. [Abstract (http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=AbstractPlus&list_uids=16239624&query_hl=19&itool=pubmed_docsum) ]
  9. Li H, Romieu I, Sienra-Monge J-J, Ramirez-Aguilar M, del Rio-Navarro BE, Kistner EO, Gjessing HK, Lara-Sanchez IC, Chiu G, London SJ. Genetic polymorphisms in arginase I and II and childhood asthma and atopy. Journal of Allergy and Clinical Immunology. 117:119-126, 2006. [Abstract (http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=AbstractPlus&list_uids=16387594&query_hl=24&itool=pubmed_docsum) ]
  10. Levan TD, Koh WP, Lee HP, Koh D, Yu MC, London SJ. Vapor, Dust and Smoke Exposure in Relation to Adult-Onset Asthma and Chronic Respiratory Symptoms: The Singapore Chinese Health Study. American Journal of Epidemiology. 163:1118-1128, 2006. Epub 2006 May 17. [Abstract (http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=AbstractPlus&list_uids=16707657&query_hl=27&itool=pubmed_docsum) ]
  11. Elliott L, Longnecker MP, Kissling GE, London SJ. Volatile organic compounds and pulmonary function in the Third National Health and Nutrition Examination Survey, 1988-1994. Environmental health perspectives 114(8):1210-1214, 2006. [Abstract (http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16882527) ]
  12. Romieu I, Ramirez-Aguilar M, Sienra-Monge JJ, Moreno-Macias H, Del Rio-Navarro BE, David G, Marzec J, Hernandez-Avila M, London S. GSTM1 and GSTP1 and respiratory health in asthmatic children exposed to ozone. Eur Respir J. 28(5):953-959, Nov 2006. Epub 2006 Jul 26. [Abstract (http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=AbstractPlus&list_uids=16870661&query_hl=33&itool=pubmed_docsum) ]
  13. Wu H, Romieu I, Sienra-Monge JJ, del Rio-Navarro BE, Anderson DM, Dunn EW, Steiner LL, Lara-Sanchez I, London SJ. Parental Smoking Modifies the Relation between Genetic Variation in Tumor Necrosis Factor-? (TNF) and Childhood Asthma.  Environmental Health Perspectives, in press.
  14. Li H, Romieu I, Wu H, Sienra-Monge JJ, Ramírez-Aguilar M, del Río-Navarro BE, Lara-Sánchez I, Kistner EO, Gjessing HK, London SJ. Genetic polymorphisms in transforming growth factor beta-1 (TGFB1) and childhood asthma and atopy. Human Genetics. Epub Feb 28 2007. [Abstract (http://www.ncbi.nlm.nih.gov/pubmed/17333284) ]
  15. Kan H, Heiss G, Rose KM, Whitsel E, Lurmann F, London SJ. Traffic exposure and lung function in adults: the Atherosclerosis Risk in Communities Study. Thorax. 62:873-879, 2007. [Abstract (http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17442705) ]
  16. Bennett WD, Hazucha MJ, Folinsbee LJ, Bromberg PA, Kissling GE, London SJ. Acute pulmonary function response to ozone(O3) in young adults as a function of body mass index (BMI). Inhalation toxicology. 19(14):1147-1154, 2007. [Abstract (http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17987466) ]
  17. Hoppin JA, Valcin M, Henneberger PK, Kullman GJ, Umbach DM, London SJ, Alavanja MCR, Sandler DP. Pesticide use and chronic bronchitis among farmers in the Agricultural Health Study. American journal of industrial medicine 50(12):969-979, 2007. [Abstract (http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17975796) ]
  18. Kan H, Stevens J, Heiss G, Rose KM, London SJ. Dietary fiber, lung function and chronic obstructive pulmonary disease in the Atherosclerosis Risk in Communities Study. American journal of epidemiology. 167(5):570-578, 2007. [Abstract (http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=18063592) ]
  19. Elliott L, Henderson J, Northstone K, Chiu GY, Dunson D, London SJ. Prospective study of breastfeeding in relation to wheeze, atopy, and bronchial hyperresponsiveness in the Avon Longitudinal Study of Parents and Children (ALSPAC). Lancet. 122(1):49-54, 2008. [Abstract (http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=18468669) ]
  20. Kan H, Heiss G, Rose KM, Whitsel EA, Lurmann F, London SJ. Prospective analysis of traffic exposure as a risk factor for incident coronary heart disease: the Atherosclerosis Risk in Communities (ARIC) study. Environmental health perspectives. 116(11):1463-1468, 2008. [Abstract (http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=19057697) ]
  21. Håberg SE, London SJ, Stigum H, Nafstad P, Nystad W. Folic acid supplements in pregnancy and early childhood respiratory health. Archives of disease in childhood. 94(3):180-184, 2009. [Abstract (http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=19052032) ]
  22. Wu H, Romieu I, Sienra-Monge JJ, del Rio-Navarro BE, London SJ. Genetic variation in ORM1-like 3 (ORMDL3) and gasdermin-like (GSDML) and childhood asthma. Allergy. 64(4):629-635, 2009. [Abstract (http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=19133921) ]
  23. Hancock DB, Romieu I, Shi M, Sienra-Monge JJ, Wu H, Chiu GY, Li H, del Rio-Navarro BE, Eng C, Chapela R, Burchard EG, Tang H, Sullivan PF, London SJ. Genome-wide association study implicates chromosome 9q21.31 as a susceptibility locus for asthma in mexican children. PLoS genetics. 5(8):e1000623, 2009. [Abstract (http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=19714205) ]
  24. Hoppin JA, Umbach DM, London SJ, Henneberger PK, Kullman GJ, Coble J, Alavanja MCR, Beane Freeman LE, Sandler DP. Pesticide use and adult-onset asthma among male farmers in the Agricultural Health Study. The European respiratory journal 34(6):1296-1303, 2009. [Abstract (http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=19541724) ]
  25. Wu H, Romieu I, Shi M, Hancock DB, Li H, Sienra-Monge JJ, Chiu GY, del Rio-Navarro BE, London SJ. Evaluation of candidate genes in a genome-wide association study of childhood asthma in Mexicans. The Journal of allergy and clinical immunology. 125(2):321-327, 2010. [Abstract (http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=19910030) ]
  26. Hancock DB, Eijgelsheim M, Wilk JB, Gharib SA, Loehr LR, Marciante KD, Franceschini N, van Durme YMTA, Chen T, Barr RG, Schabath MB, Couper DJ, Brusselle GG, Psaty BM, van Duijn CM, Rotter J, Uitterlinden AG, Hofman A, Punjabi NM, Rivadeneira F, Morrison AC, Enright PL, North KE, Heckbert SR, Lumley T, Stricker BHC, O'Connor GT, London SJ. Meta-analyses of genome-wide association studies identify multiple loci associated with pulmonary function. Nature genetics. 42(1):45-52, 2010. [Abstract (http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=20010835) ]
  27. Tang H, Siegmund DO, Johnson N, Romieu I, London SJ. Joint testing of genotype and ancestry association in admixed families. Genetic epidemiology. 34(8):783-791, 2010. [Abstract (http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=21031451) ]
  28. Itsara A, Wu H, Smith J, Nickerson DA, Romieu I, London S, Eichler EE. De Novo Rates and Selection of Large Copy Number Variation. Genome research. 20(11):1469-1481, 2010. [Abstract (http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=20841430) ]
  29. Aschard H, Hancock DB, London SJ, Kraft P. Genome wide meta-analysis of joint tests for genetic and gene-environment interaction effects. Human heredity. 70(4):292-300, 2010. [Abstract (http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=21293137) ]
  30. Kan H, Folsom AR, Cushman M, Rose KM, Rosamond WD, Liao D, Lurmann F, London SJ. Traffic exposure and incident venous thromboembolism in the Atherosclerosis Risk in Communities (ARIC) Study. Journal of thrombosis and haemostasis. 9(4):672-678, 2011. [Abstract (http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=21255249) ]
  31. Håberg SE, London SJ, Nafstad P, Nilsen RM, Ueland PM, Vollset SE, Nystad W. Maternal folate levels in pregnancy and asthma in children at age three years. Journal of Allergy and Clinical Immunology. 127(1):262-264, 2011. [Abstract (http://www.sciencedirect.com/science?_ob=ArticleURL&_udi=B6WH4-51HCR8S-3&_user=10380239&_coverDate=01%2F31%2F2011&_rdoc=1&_fmt=high&_orig=gateway&_origin=gateway&_sort=d&_docanchor=&view=c&_acct=C000000150&_version=1&_urlVersion=0&_userid=10380239&md5=3da396591a4ce6c9e20b1384cacf234b&searchtype=a) ]
  32. Hancock DB, London SJ, CHARGE Pulmonary Function Working Group. Determinants of lung function, COPD, and asthma. The New England journal of medicine. 364(1):86-87, 2011. [Abstract (http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=21208119) ]
  33. Shi M, London SJ, Chiu GY, Hancock DB, Zaykin D, Weinberg CR. Using imputed genotypes for relative risk estimation in case-parent studies. American journal of epidemiology 173(5):553-559, 2011. [Abstract (http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=%2021296892) ]
  34. Furu K, Karlstad O, Skurtveit S, Håberg SE, Nafstad P, London SJ, Nystad W. High validity of mother-reported use of antiasthmatics among children: a comparison with a population-based prescription database. Journal of clinical epidemiology 64(8):878-884, 2011. [Abstract (http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=21232920) ]
  35. Hancock DB, Haberg SE, Furu K, Whitworth KW, Nafstad P, Nystad W, London SJ. Oral contraceptive pill use before pregnancy and respiratory outcomes in early childhood. Pediatric allergy and immunology 22(5):528-536, 2011. [Abstract (http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=21294776) ]
  36. Schauberger EM, Ewart SL, Arshad SH, Huebner M, Karmaus W, Holloway JW, Friderici KH, Ziegler JT, Zhang H, Rose-Zerilli MJ, Barton SJ, Holgate ST, Kilpatrick JR, Harley JB, Lajoie-Kadoch S, Harley IT, Hamid Q, Kurukulaaratchy RJ, London SJ, Burchard EG, Langefield CD, Wills-Karp M. Identification of ATPAF1 as a novel candidate gene for asthma in children. Journal of Allergy and Clinical Immunology  128(4):753-760.e11, 2011. [Abstract (http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=21696813) ]  
  37. Butler LM, Kan H, London SJ. Dietary fiber prevents both morbidity and mortality from respiratory disease. Archives of internal medicine  171(12):1123, 2011. [Abstract (http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=21709119) ]  


Back to top Back to top


 
Last Reviewed: December 06, 2011