Does age affect methylation at each of the three sites

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Reference no: EM131207261

Case Study 1-

In an experiment to determine the efficacy of a proton pump inhibitor (PPI) drug in reducing the frequency of nocturnal gastrointestinal reflux episodes, 12 patients suffering from gastro-eosophageal reflux disease (GERD) were repeatedly treated over a series of 5 day periods with either a placebo, 10mg, 20 mg or 40 mg daily doses of the PPI, with a 7 day washout period between treatment periods. Patients were allocated the 4 treatments in random order. The number of gastric reflux episodes per hour was measured for each patient using 24 hour oesophageal pH monitoring during an initial 5 day pre-treatment baseline period and during each of the 4 treatment periods.

Table 1 shows the change in the number of gastric reflux episodes, for each patient, during each of the 4 treatment periods, relative to the pre-treatment baseline.

Table 1.

 

Change in no. reflux episodes / hour

Patient

Placebo

10mg

20mg

40mg

1

-4.53

-9.06

-6.68

-0.9

2

-1.28

-12.18

-16.33

-15.7

3

2.42

0.75

-0.74

-0.58

4

1.39

-0.67

-1.68

-1.55

5

0.17

-0.44

1.9

-8.24

6

0.17

-0.9

-1.4

-1.4

7

12.48

-2.48

-3.55

-4.67

8

-1.36

-1.46

-1.65

-1.55

9

2.41

0.12

0

0

10

-0.77

1.41

-1.16

-2.75

11

2.22

-0.04

-0.71

0.87

12

0.04

-0.06

0.17

-1.88

From: Bradstreet, T.E. (1991) "Some Favorite Data Sets from Early Phases of Drug Research." Proceedings of the Section on Statistical Education of the American Statistical Association.

Answer the following questions.

a) State what statistical test was used and explain why you chose the test.

b) Paste in the key results from the statistical test.

c) Is the PPI drug effective at reducing the number reflux episodes and, if so, at which doses? Support your answer using the results from the statistical test.

d) If the drug is effective, is there evidence of a dose-response relationship?

e) Plot a figure (with an appropriate figure legend) illustrating the results of the experiment.

Case Study 2-

In an experiment to determine the pharmacokinetics of a new drug, a 2g dose of the drug was injected into each of a group of 30 subjects (7 elderly (aged ≥ 65 years) males, 7 elderly females, 8 young (aged ≥ 65 years) males, 8 young females).

Table 2 shows the measured plasma concentration of the drug, 12 hours after an intravenous injection of 2g of the drug.

Table 2.

Age

Sex

Plasma Conc.
mg/ml

 

Age

Sex

Plasma Conc.
mg/ml

Elderly

Male

22.1

 

Young

Male

15.2

Elderly

Male

22.4

 

Young

Male

17.1

Elderly

Male

38

 

Young

Male

13.6

Elderly

Male

34.6

 

Young

Male

23.6

Elderly

Male

30.4

 

Young

Male

23.4

Elderly

Male

26.4

 

Young

Male

17.1

Elderly

Male

31.5

 

Young

Male

13.2

Elderly

Female

28.7

 

Young

Male

16.8

Elderly

Female

24.8

 

Young

Female

18.5

Elderly

Female

23.2

 

Young

Female

16.4

Elderly

Female

24

 

Young

Female

18.1

Elderly

Female

18.1

 

Young

Female

16.3

Elderly

Female

26.3

 

Young

Female

14

Elderly

Female

23.1

 

Young

Female

13.9

 

 


 

Young

Female

16.5

 

 


 

Young

Female

9

From: Bradstreet, T. E. and Short, T. H. (2001) "Favorite Data Sets from Early Phases of Drug Research - Part 5." Proceedings of the Section on Statistical Education of the American Statistical Association.

Answer the following questions.

a) State what statistical test was used and explain why you chose the test.

b) Paste in the key results from the statistical test.

c) Does age or gender affect the pharmacokinetics of the drugs? Support your answer using the results from the statistical test.

d) Plot a figure (with an appropriate figure legend) illustrating the results of the experiment.

Case Study 3-

In a study of the effect of aging on DNA methylation, DNA was extracted from blood samples from 65 donors, with ages ranging from 11 to 72 years, and the percentage methylation at a range of CpG sites determined using MS-RDA (methylation-sensitive representational difference analysis).

Table 3 lists the measured percentage methylation at CpG sites on 3 three genes (GPR137, ZIC4, ZDHHC22) and the age of the donor.

Table 3.

GPR137


ZIC4


ZDHHC22

Age
(years)

Methylation
(%)


Age
(years)

Methylation
(%)


Age
(years)

Methylation
(%)

11.04

89.87


15.26

90.09


60.18

89.59

14.17

89.73


17.72

90.09


63.21

89.74

22.16

89.87


19.3

90.09


65.71

89.74

25.46

89.87


11.05

79.74


72.14

89.44

36.92

90.01


13.16

79.88


70.54

79.62

46.82

89.73


14.39

79.88


67.5

79.62

12.95

79.89


17.19

79.88


65.89

79.62

14.69

80.17


22.11

79.88


55.89

79.62

16.95

80.17


24.91

79.88


51.61

79.77

19.03

80.17


27.19

79.88


48.39

79.62

21.46

80.17


32.63

80.03


40

79.62

24.94

80.17


34.56

80.17


37.68

69.21

34.14

80.31


36.14

80.17


39.64

69.35

37.27

80.31


38.25

80.17


41.96

69.35

39.88

80.31


40.35

80.17


48.21

69.5

46.65

80.03


14.04

69.97


29.46

59.38

60.37

80.03


21.4

69.83


33.75

59.68

14.17

70.04


27.19

69.68


38.04

59.97

26.85

69.76


29.82

69.83


39.82

59.97

32.93

69.9


33.68

70.12


41.07

59.68

33.62

69.9


38.25

69.97


43.21

59.53

34.32

69.76


39.82

69.97


47.5

59.68

38.14

70.04


41.75

69.97


56.07

59.97

40.05

69.76


43.16

69.97


51.25

49.56

47.87

69.9


27.02

59.77


46.79

49.56

17.99

59.91


33.16

59.91


43.21

49.56

33.45

60.2


37.19

59.77


41.43

49.56

37.79

60.06


40.7

59.77


39.64

49.71

41.44

60.06


43.33

59.48


37.32

49.85

48.21

60.2


46.84

59.91


32.86

49.85

56.03

60.2


48.25

59.91


29.29

49.56

62.98

60.2


30.35

50.15


26.43

49.56

67.15

59.91


34.04

50.15


21.25

39.59

27.02

50.07


40

50.29


25.18

39.59

30.15

49.93


41.4

50.29


26.79

39.59

35.88

50.07


43.86

50.15


36.79

39.44

37.97

50.07


46.84

50.15


43.39

39.44

40.22

49.93


48.6

50.15


25

29.62

41.79

49.93


51.23

50.15


18.93

29.62

43.87

49.79


32.98

40.23


17.14

29.77

48.21

49.79


37.54

40.09


20.36

19.65

50.65

49.93


48.42

40.38


15

19.65

29.98

39.66


56.49

40.23


13.39

19.65

40.05

39.51


60.18

40.09


12.5

19.65

41.61

39.37


50.88

30.03


10.54

9.677

43

39.94


62.98

30.03


13.57

9.531

47.87

40.09


67.19

30.03




65.93

39.94


66.49

19.97




43

30.1


70

20.12




50.99

30.1


67.37

10.06




65.76

30.1


71.93

10.06




72.53

19.54







66.8

9.986







70.27

9.843







From: Yi S.H. et al (2014) Isolation and identification of age-related DNA methylation markers for forensic age-prediction. Forensic Sci Int Genet. 117-25.

Answer the following questions.

a) State what statistical test(s) were used to analyse the data and explain why you chose the test.

b) Paste in the key results from the statistical test(s).

c) Does age affect methylation at each of the three sites and in what way? Support your answer using the results from the statistical test.

d) Plot a figure (with an appropriate figure legend) illustrating the results of the experiment.

e) Develop a model for predicting age from DNA methylation and state the best fitting equation predicting age from % methylation.

Reference no: EM131207261

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