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Rare Diseases Epidemiology pp 17–39Cite as

Rare Diseases Epidemiology Research

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Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 686))

Abstract

Rare Diseases Epidemiology is a novel action field still largely unexplored. However, Rare Diseases is a topic of growing interest at world level. The aims of this chapter are to revise useful epidemiological tools and define areas where epidemiology can help improve the rare disease knowledge, and facilitate policy decisions taking into account the real burden of rare diseases in society. This chapter also seeks to describe: the problems of coding and classification of diseases, measuring disease frequency, the study designs and association studies, the causality, the evolution from descriptive to epigenetic epidemiology and the natural history of disease. One of the major challenges facing analytical epidemiology and clinical epidemiological research into rare diseases is that genes can be involved in both aetiology and prognosis. Despite the many similarities between genetic association studies and classic observational epidemiological studies, the former pose several specific limitations, including an unprecedented volume of new data and the likelihood of very small individual effects, as well other limitations. Selecting the appropriate pathway from among all those available, i.e. the one that best relates genes from the various known regions and disease mechanisms, is crucial for the success of this type of studies

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References

  1. Alison A, Motsinger-Reif AA, Reif DM, Fanelli TJ, Ritchie MD (2008) Comparison of analytical methods for genetic association studies. Genet Epidemiol 32:767–778

    Article  Google Scholar 

  2. Bermejo E, Cuevas L, Grupo Periférico del ECEMC, Martínez-Frías ML (2009) Vigilancia epidemiológica de anomalías congénitas en España: Análisis de los datos del registro del ECEMC en el período 1980–2008. Bol ECEMC Rev Dismor Epidemiol V(8):4–91. [access: January 2010]. Available: http://bvs.isciii.es/mono/pdf/CIAC_08.pdf

  3. Boutron I, Moher D, Altman DG, Schulz KF, Ravaud P; CONSORT Group (2008) Methods and processes of the CONSORT Group: example of an extension for trials assessing nonpharmacologic treatments. Ann Intern Med 148(4):W60–W66

    PubMed  Google Scholar 

  4. Burton PR, Tobin MD, Hopper JL (2005) Key concepts in genetic epidemiology. Lancet 366:941–951

    Article  PubMed  Google Scholar 

  5. Breslow NE, Lumley T, Ballantyne CM, Chambless LE, Kulich M (2009) Using the whole cohort in the analysis of case-cohort data. Am J Epidemiol 169(11):1398–1405

    Article  PubMed  Google Scholar 

  6. Bruce S, Hannula-Jouppi K, Peltonen J, Kere J, Lipsanen-Nyman M (2009) Clinically distinct epigenetic subgroups in Silver–Russell syndrome: the degree of H19 hypomethylation associates with phenotype severity and genital and skeletal anomalies. J Clin Endocrinol Metab 94(2):579–587

    Article  PubMed  CAS  Google Scholar 

  7. Campbell MK, Elbourne DR, Altman DG; CONSORT Group (2004) CONSORT statement: extension to cluster randomised trials. BMJ 328(7441):702–708

    Article  PubMed  Google Scholar 

  8. Centers for Disease Control (CDC) (1990) Guidelines for investigating clusters of health events. MMWR 39(RR-11):1–16. [access: January 2010]. Available: http://wonder.cdc.gov/wonder/prevguid/m0001797/m0001797.asp

  9. Commission of the European Communities (1999) Decision No 1295/1999/EC of the European Parliament and of the Council of 29 April 1999 adopting a programme of Community action on rare diseases within the framework for action in the field of public health (1999–2003). April 1999 [access: January 2010]. Available: http://eur-lex.europa.eu/pri/en/oj/dat/1999/l_155/l_15519990622en00010005.pdf

  10. Commission of the European Communities. Communication from the Commission to the European Parliament, the Council, the European Economic and Social Committee and the Committee of the Regions on Rare Diseases: Europe’s challenges (2008) [access: January 2010]. Available: http://ec.europa.eu/health/ph_threats/non_com/docs/rare_com_en.pdf

  11. Council Recommendation of 8 June 2009 on an action in the field of rare diseases (2009/C 151/02) Official Journal of the European Union, C 151/7- C 151/10 [access: January 2010]. Available: http://eur-lex.europa.eu/LexUriServ/LexUriServ.do?uri=OJ:C:2009:151:0007:0010:en:pdf

  12. Davey Smith G, Ebrahim S, Lewis S, Hansell AL, Palmer LJ, Burton PR (2005) Genetic epidemiology and public health: hope, hype, and future prospects. Lancet 366(9495): 1484–1498

    Article  PubMed  Google Scholar 

  13. DG Health and Consumer Protection Programme of Community action in the field of public health (2003–2008) [access: January 2010]. Available: http://ec.europa.eu/health/ph_programme/programme_en.htm

  14. DisMod II. Software developed by J. Barendregt, Department of Public Health, Erasmus University Holland, in collaboration with the WHO. [Access January 2010]. Available: http://www.who.int/healthinfo/global_burden_disease/tools_software/en/index.html

  15. E-RARE. ERA-Net for research programs on rare diseases. http://www.e-rare.eu/

  16. EUGLOREH 2007 (2009) Chapter 9.1.2 Congenital malformations. In: The Status of Health in the European Union: towards a healthier Europe, EU Public Health Programme Project, Global Report on the Health Status in the European Union. [access: January 2010]. Available: http://www.eugloreh.it/ActionPagina_993.do

  17. EUROCAT-Cluster Advisory Service (2003) Cluster Investigation Protocols. [access: January 2010]. Available: http://www.eurocat.ulster.ac.uk/clusterinvprot.html

  18. EUROCAT (2008) EUROCAT Statistical Monitoring Protocol. http://www.eurocat.ulster.ac.uk/pubdata/Stat-Mon.html

  19. EUROPLAN. The European Project for Rare Diseases National Plans Development. http://www.europlanproject.eu/

  20. European Medicines Agency (EMEA) (2000) Regulation (EC) No 141/2000 of the European Parliament and of the Council of 16 December 1999 on orphan medicinal products [access: January 2010]. Available: http://eur-lex.europa.eu/LexUri-Serv/site/es/oj/2000/l_018/l_01820000122es00010005.pdf

  21. European Medicines Agency (EMEA) (2002) Points to consider on the calculations and reporting of prevalence of a condition for orphan designation. London 26 Mar 2002 COMP/ 436/01. [access: January 2010]. Available: http://www.ema.europa.eu/pdfs/human/comp/043601.pdf

  22. Faucett WA, Hart S, Pagon RA, Neall LF, Spinella G (2008) A model program to increase translation of rare disease genetic tests: collaboration, education, and test translation program. Genet Med 10(5):343–348

    Article  PubMed  CAS  Google Scholar 

  23. Feinberg AP, Tycko B (2004) The history of cancer epigenetics. Nat Rev Cancer 4(2): 143–153

    Article  PubMed  CAS  Google Scholar 

  24. Feinberg AP (2010) Genome-scale approaches to the epigenetics of common human disease. Virchows Arch 456(1):13–21

    Article  PubMed  CAS  Google Scholar 

  25. Foley DL, Craig JM, Morley R, Olsson CA, Dwyer T, Smith K, Saffery R (2009) Prospects for Epigenetic Epidemiology. Am J Epidemiol 169(4):389–400

    Article  PubMed  Google Scholar 

  26. Greenhouse JB (2009) Commentary: cornfield, epidemiology and causality. Int J Epidemiol 38:1199–1201

    Article  PubMed  Google Scholar 

  27. Greenland S, Brumback B (2002) An overview of relations among causal modelling methods. Int J Epidemiol 31(5):1030–1037

    Article  PubMed  Google Scholar 

  28. Håberg SE, London SJ, Stigum H, Nafstad P, Nystad W (2009) Folic acid supplements in pregnancy and early childhood respiratory health. Arch Dis Child 94:180–184.

    Article  PubMed  Google Scholar 

  29. Hampton T (2006) Rare disease research gets boost. JAMA 295(24):2836–2838

    Article  PubMed  CAS  Google Scholar 

  30. Hennekens CH, Buring JE (1987) Epidemiology in medicine. Little, Brown and Company, Boston, MA

    Google Scholar 

  31. Hill AB (1965) The environment and disease: association or causation? Proc Roy Soc Med 58:295–300

    PubMed  CAS  Google Scholar 

  32. Hobbs CA, Hopkins SE, Simmons CJ (2001) Sources of variability in birth defects prevalence rates. Teratology 64 (Suppl 1):S8–S13

    Article  PubMed  Google Scholar 

  33. International Conferences on Rare Diseases and Orphan Drugs (ICORD). http://www.icord.se/

  34. Ioannidis JP (2007) Genetic and molecular epidemiology. J Epidemiol Community Health 61:757–758

    Article  PubMed  Google Scholar 

  35. Ioannidis JP, Boffetta P, Little J, O’Brien TR, Uitterlinden AG, Vineis P, Balding DJ, Chokkalingam A, M Dolan SM, Flanders WD, Higgins Julian PT, McCarthy MI, McDermott David H, Page Grier P, Rebbeck TR, Seminara D, Khoury MJ (2008) Assessment of cumulative evidence on genetic associations: interim guidelines. Int J Epidemiol 37(1):120–132

    Article  PubMed  Google Scholar 

  36. Jorgensen TJ, Ruczinski I, Kessing B, Smith MW, Shugart YY, Alberg AJ (2009) Hypothesis-driven candidate gene association studies: practical design and analytical considerations. Am J Epidemiol 170(8):986–993

    Article  PubMed  Google Scholar 

  37. Khoury MJ, Little J, Gwinn M, Ioannidis JP (2007) On the synthesis and interpretation of consistent but weak gene-disease associations in the era of genome-wide association studies. Int J Epidemiol 36:439–445

    Article  PubMed  Google Scholar 

  38. Kleinbaum DG, Kupper LL, Morggenstern H (1982) Epidemiologic Research. Principles and quantitative methods. Van Nostrand Reinhold, New York

    Google Scholar 

  39. Last J (2001) A dictionary of epidemiology, 4th edn. Oxford University Press, New York

    Google Scholar 

  40. Little J, Higgins JPT, Ioannidis JPA, Moher D, Gagnon F, von Elm E, Khoury MJ, et al (2009) STrengthening the REporting of Genetic Association Studies (STREGA) An Extension of the STROBE Statement. Plos Med 6(2):151–163.

    Article  Google Scholar 

  41. Martínez-Frías ML (2007) Postmarketing analysis of medicines: methodology and value of the Spanish case-control study and surveillance system in preventing birth defects. Drug Safety 30(4):307–316

    Article  PubMed  Google Scholar 

  42. Mason CA, Kirby RS, Sever LE, Langlois PH (2005) Prevalence is preferred measures of frequency of birth defects. Birth Defects Res A Clin Mol Teratol 73(10):690–692

    Article  PubMed  CAS  Google Scholar 

  43. Miettinen OS (2004) Epidemiology: quo vadis? Eur J Epidemiol 19(8):713–718

    Article  PubMed  Google Scholar 

  44. Moher D, Schulz KF, Altman DG, CONSORT Group (2001) The CONSORT statement: revised recommendations for improving the quality of reports of parallel-group randomised trials. Lancet 357:1191–1194

    Article  PubMed  CAS  Google Scholar 

  45. Murray CJ, Acharya AK (1997) Understanding DALYs (disability-adjusted life years) J Health Econ. 16(6):703–730

    Article  PubMed  CAS  Google Scholar 

  46. National Institutes of Health. Library National of Medicine (2010) Medical Subject Headings. http://www.nlm.nih.gov/mesh/meshhome.html

  47. Online Mendelian Inheritance in Man (OMIM): http://www.ncbi.nlm.nih.gov/Omim/

  48. Orphanet Report Series (2010) Prevalence of rare diseases: bibliographic data. [access: June 2010]. Available: http://www.orpha.net/orphacom/cahiers/docs/GB/Prevalence_of_rare_diseases_by_alphabetical_list.pdf

  49. ORPHANET (2010). [Access: June, 2010]: http://www.orpha.net/

  50. Rare Diseases Task Force (RDTF) Working Group Coding, classification and data confidentiality: [access: January 2010]. Available: http://www.orpha.net/testor/cgi-bin/OTmain.php?PHPSESSID=cea107c54dc7d292c2e5775ca686dd16&UserCell=workingGroup

  51. RARECARE. Surveillance of Rare Cancers in Europe. Rationale & Questions for Consensus [Access January 2010]. Available: http://www.rarecare.eu/rarecancers/Rationales_and_questions_for_consensus_24-12-08.pdf

  52. Rose G (1985) Sick individuals and sick populations. Inter J Epidemiol 14:32–38

    Article  CAS  Google Scholar 

  53. Rothman KJ, Greenland S, Lash TL (2008) Modern epidemiology. Lippincott Williams & Wilkins, Philadelphia

    Google Scholar 

  54. Sanderson S, Tatt ID, Higgins JP (2007) Tools for assessing quality and susceptibility to bias in observational studies in epidemiology: a systematic review and annotated bibliography. Int J Epidemiol 36:666–676

    Article  PubMed  Google Scholar 

  55. Schieppati A, Henter JI, Daina E, Aperia A (2008) Why rare diseases are an important medical and social issue. Lancet 371(9629):2039–241

    Article  PubMed  Google Scholar 

  56. Systematized Nomenclature of Medicine (SNOMED) http://www.ihtsdo.org/snomed-ct/

  57. Thomas DC (2006) Are we ready for genome-wide association studies? Cancer Epidemiol Biomarkers Prev 15:595–598

    Article  PubMed  Google Scholar 

  58. Vandenbroucke JP, von Elm E, Altman DG, Gøtzsche PC, Mulrow CD, Pocock SJ, Poole C, Schlesselman JJ, Egger M; STROBE initiative (2007) Strengthening the reporting of observational studies in epidemiology (STROBE): explanation and elaboration. Ann Intern Med 147(8):163–194 W.

    Google Scholar 

  59. Villaverde-Hueso A, Sánchez-Valle E, Álvarez E, Morant C, Carreira PE, Martín-Arribas MC, Gènova R, Ramírez-González A, Posada de la Paz M (2007) Estimating the Burden of Scleroderma Disease in Spain. J Rheumatol 34(11):2236–2242

    PubMed  Google Scholar 

  60. von Elm E, Altman D G, Egger M, Pocock SJ, Gøtzsche PC, Vandenbroucke JP for the STROBE Initiative (2008) Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) statement: guidelines for reporting observational studies. J Clin Epidemiol 61(4):344–349

    Article  Google Scholar 

  61. von Elm E, Moher D, Little J and STREGA collaboration (2009) Reporting genetic association studies: the STREGA statement. Lancet 374(9684):98–100

    Article  Google Scholar 

  62. Wacholder S (2009) Nested case-control studies: commentary. Bias in Full Cohort and Nested Case-Control Studies? Epidemiology 3:339–340

    Article  Google Scholar 

  63. Washington State Department of Health (2007) Guidelines for Investigating Clusters of Chronic Disease and Adverse Birth Outcomes. [access: January 2010]. Available: http://www.doh.wa.gov/EHSPHL/Epidemiology/NICE/publications/ClusterProtocol.pdf

  64. Webb P, Bain C, Pirozzo S (2005) How long is a piece of string? Measuring diseases frequency. In: Webb P, Bain C, Pirozzo S (eds) Essential epidemiology: an introduction for students and health proffesionals. Cambridge University Press, Cambridge, pp 28–60

    Google Scholar 

  65. WHOFIC Network. Production of ICD-11: the overall revision process. March 2007 [access January 2010]. Available: http://www.who.int/classifications/icd/ICDRevision.pdf

  66. Wolf SH (2008) The meaning of translational research and why it matters. JAMA 299(2): 211–213

    Article  Google Scholar 

  67. World Health Organization. International Statistical Classification of Diseases and Related Health Problems 10th Revision. Version for 2006. [access: January 2010]. Available: http://www.who.int/classifications/apps/icd/icd10online/

  68. Wynne JW, Harris J, Bentley S, Stierman L (1999) California Birth Defects Monitoring Program (CBDMP). Investigating clusters of birth defects: a systematic approach. [access: January 2010]. Available: http://www.cbdmp.org/pdf/investbdclusters.pdf

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Author information

Authors and Affiliations

  1. Instituto de Investigación en Enfermedades Raras (IIER), Instituto de Salud Carlos III and Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), Monforte de Lemos, 5, 28029, Madrid, Spain

    Manuel Posada de la Paz, Ana Villaverde-Hueso PharmD, Verónica Alonso PhD & Ignacio Abaitua-Borda MD

  2. Head of Division, Division of Biostatistics and Epidemiology, Department of Preventive Medicine, University of Debrecen, Debrecen, Hungary

    Sándor János (Faculty of Public Health)

  3. Epidemiology Department, Public Health Authority, and Centro Superior de Investigación en Salud Pública (Public Health Research Centre), Valencia, Spain

    Óscar Zurriaga MD, PhD

  4. Head of Service, Environmental and Cancer Epidemiology, Centro Nacional de Epidemiología. Instituto de Salud Carlos III and CIBER de Salud Pública (CIBERESP), Madrid, Spain

    Marina Pollán MD, PhD

Authors
  1. Manuel Posada de la Paz
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  2. Ana Villaverde-Hueso PharmD
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  3. Verónica Alonso PhD
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  4. Sándor János
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  5. Óscar Zurriaga MD, PhD
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  6. Marina Pollán MD, PhD
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  7. Ignacio Abaitua-Borda MD
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Corresponding author

Correspondence to Manuel Posada de la Paz .

Editor information

Editors and Affiliations

  1. , Instituto de Investigaciñon en Enfermeda, Instituto de Salud Carlos III, Monforte de Lemos 5, Madrid, 28029, Spain

    Manuel Posada de la Paz

  2. , Office of Rare Diseases Research, National Institutes of Health, Executive Boulevard 6100, Bethesda, 20892-7518, USA

    Stephen C. Groft

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de la Paz, M.P. et al. (2010). Rare Diseases Epidemiology Research. In: Posada de la Paz, M., Groft, S. (eds) Rare Diseases Epidemiology. Advances in Experimental Medicine and Biology, vol 686. Springer, Dordrecht. https://doi.org/10.1007/978-90-481-9485-8_2

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