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Genetic epidemiology


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Genetic epidemiology

  1. 1. MBBS Year2 - GeneticEpidemiology 3 March 2011 Page 1 of 7 When genetic epidemiology meets a patient Your patient Brian Simpson,a45 yearoldbus driver,hasmade an appointmentto see you - hisGP - as he is verykeen todiscusshiscardiovascular health. He has no previousmedical historyexceptappendicitisinhis teens. He ismarriedwithtwochildren,liveswithhiswife,smokes around10 cigarettesaday anddrinksonlyat weekends. Part I - Assessing cardiovascular risk, the traditional way Your practice uses the Framingham risk equation to calculate patients' risk of coronary heart disease (CHD) over the following 10 years. Mr Simpson last visited you a fortnight ago for some examinations and blood tests. Visit and, using the results below, calculate Mr Simpson's risk of a CHD event in the next 10 years, according to the Framingham equation. Simpson, Brian Mr. DOB 06/01/1966 Total cholesterol = 5.5mmol/L [normal range <6mmol/L] HDL-cholesterol = 1.1mmol/L [normal range >0.9mmol/L] Systolic blood pressure = 145mmHg [normal range 120-140mmHg] a. What is Mr Simpson's 10-year risk of a CVD event? _____________________ b. Is this i. Relative risk  ii. Absolute risk 
  2. 2. MBBS Year2 - GeneticEpidemiology 3 March 2011 Page 2 of 7 c. Look at the table of 10-year CHD risk below. Is his risk higher, lower, or similar compared to the population average? i. Lower  ii. Similar  iii. Higher  Age (yrs) Average 10yr CHD risk 30-34 3% 35-39 5% 40-44 7% 45-49 11% 50-54 14% 55-59 16% 60-64 21% 64-69 25% 70-74 30% d. What other information would you like to know about Mr Simpson that might influence his risk of CHD? __________________________________________ __________________________________________ __________________________________________ __________________________________________ Mr Simpson mentions that his father had died last year after a heart attack, and his grandfather had died similarly about 20 years before. e. Can we infer that CHD runs in Mr Simpson's family? i. Yes  ii. No  f. Is this 'heredity' due entirely to genes shared between family members? i. Yes  ii. No 
  3. 3. MBBS Year2 - GeneticEpidemiology 3 March 2011 Page 3 of 7 g. What other risk factors might Mr Simpson have 'inherited' from his father? __________________________________________ __________________________________________ __________________________________________ __________________________________________ Part II - Novel methods for assessing cardiovascular risk Mr Simpson rummages in his coat and pulls out a letter from 23andMe - a personal genetic testing service. He tells you that his report says he has 'a gene for heart disease' and wants to know whether he should be worried. Part of the report is shown below: a. According to this report, what is Mr Simpson's, i. absolute risk of CHD? _________________________________ ii. relative risk of CHD? _________________________________
  4. 4. MBBS Year2 - GeneticEpidemiology 3 March 2011 Page 4 of 7 b. Is his absolute risk according to23andMe substantially different from the risk you calculated using the Framingham score? i. Yes  ii. No  One of the reports of the genetic variant used in this report (rs10757278) was in Science in 2007 (Helgadottir et al. Science 2007 316:1491-93 PubMed ID 17478679). In this genome-wide association study in several large groups of CHD cases and healthy controls, the single nucleotide polymorphism (SNP), rs10757278, was found to be associated with risk of coronary heart disease. Some of the results are shown below:
  5. 5. MBBS Year2 - GeneticEpidemiology 3 March 2011 Page 5 of 7 c. What is a genome-wide association study? __________________________________________________________________ __________________________________________________________________ __________________________________________________________________ d. The authors report an odds ratio (OR). What comparison is being made to calculate this odds ratio? __________________________________________________________________ __________________________________________________________________ e. The authors also report 'combined' estimates of the odds ratio (OR), which is the result of meta-analysis. Why did the authors conduct a meta-analysis in their analysis? __________________________________________________________________ __________________________________________________________________ __________________________________________________________________ f. The SNP assessed here is in a region on chromosome 9 containing genes involved in cell proliferation, apoptosis and cell ageing (CDKN2A, CDKN2B). Genes involved in what areas of physiology might you expect tobe associated with risk of CHD? __________________________________________________________________ __________________________________________________________________ Part III - Patients and their genotype a. You are talking to Mr Simpson about reducing his risk for cardiovascular disease. Based on the assessment you made so far, what recommendations would you make? __________________________________________________________________ __________________________________________________________________
  6. 6. MBBS Year2 - GeneticEpidemiology 3 March 2011 Page 6 of 7 b. Even after making recommendations, Mr Simpson appears still more concerned about his genetic risk than other factors influencing his CHD risk. Suggest two reasons of why that may be the case. __________________________________________________________________ __________________________________________________________________ c. From your understanding of geneticrisk prediction for common diseases, do you believe that Mr Simpson’s concerns are justified? i. Yes  ii. No  d. Will Mr Simpson's result from 23andMe alter your approach to his medical care? __________________________________________________________________ __________________________________________________________________ e. Regardless of your opinion, why is it important that you as healthcare provider are taking his concerns seriously? __________________________________________________________________ __________________________________________________________________ f. Suggest how Mr Simpson’s behaviourmay be affected by the genetic test result. __________________________________________________________________ __________________________________________________________________ __________________________________________________________________ __________________________________________________________________ g. Discuss two problems with using genetic data as predictor for common complex diseases such as CHD. __________________________________________________________________ __________________________________________________________________ __________________________________________________________________
  7. 7. MBBS Year2 - GeneticEpidemiology 3 March 2011 Page 7 of 7 h. Suggest two ethical and/or personal considerations Mr Simpson may be faced with as result of undergoing genetic testing. __________________________________________________________________ __________________________________________________________________ __________________________________________________________________ ________________________________________________________________________ Further reading: Hingorani AD, Shah T, Kumari M, Sofat R, Smeeth L. Translating genomics into improved healthcare. BMJ. 2010;341:c5945 McCarthy MI, Abecasis GR, Cardon LR, Goldstein DB, Little J, Ioannidis JP, et al. Genome- wide association studies for complex traits: consensus, uncertainty and challenges. Nature reviews. 2008 May;9(5):356-69. Pearson TA, Manolio TA. . How to interpret at Genome-wide Association Study. JAMA. 2008;299(11):1335-1344