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Telomeres Tell A Lot


Conventional wisdom, indeed wisdom of any form, indicates that physical activity, a.k.a. regular exercise, is good for you. In particular, intuition would imply that the risk factors for age-related diseases such as diabetes, cancer, hypertension, obesity and osteoporosis would be reduced if people were engaged in physical activity. To make a direct connection between ageing and physical activity, consider a paper in the Archives of Internal Medicine (Vol.168, No. 2, January 28, 2008), “The Association Between Physical Activity in Leisure Time and Leukocyte Telomere Length” by Cherkas, et al.
dealt with what the British call League Tables but we would call rankings.  David's [http://plus.maths.org/issue45/risk/ first column] appeared in Issue 44. Here David provides an example of a ranking where the outcomes should be pure chance but often do not look like pure chance. In his [http://plus.maths.org/issue46/risk/index.html second column] which appeared in Issue 45, David provides an example where the outcomes should be  predoinantly skill also luck plays a role and he shows how to estimate how much of a role luck plays.  In this  the discussion is similar to our discussion of  "Is poker a predominatly a game of skill or luck that we discussed in [http://chance.dartmouth.edu/chancewiki/index.php/Chance_News_29#Is_Poker_predominantly_skill_or_luck.3F Chance News 29]


“Telomeres consist of tandemly repeated DNA sequences that play an important role in the structure and function of chromosomes.”  Leukocyte telomere length (LTL) is a proxy variable for one’s biological age as opposed to one’s chronological ageThat is, the longer one’s telomeres, the younger one actually is.  Conversely, the shorter the telomeres, the more aged.
In the UK National Lottery 6 numbers are randomly chosen from the numbers from 1 to 49If you correctly predict the six numbers chosen you get a share of the jackpot.  


This study measured the telomeres of 2401 twins who were put into four mutually exclusive categories of physical activity: “Inactive,” “Light,” “Moderate,” and “Heavy” corresponding to “16 minutes, 36 minutes, 102 minutes and 199 minutes” physical activity per week, respectively.   The result after adjusting for “Age, sex, and extraction year” was that the “LTL of the most active subjects (group 4) was an average 200 (SE, 79) nt [nucleotides] longer than that of the inactive subjects (group 1)” producing a p-value of .006“This difference suggests that inactive subjects had telomeres the same length as sedentary individuals up to 10 years younger, on average.”  When more complete information was available concerning BMI (biomass index), smoking and SES (socioeconomic status) this reduced the number of subjects to 1531 from the 2401; the LTL difference increased to 213 nt and the p-value increased to .02Below are a summary table and Figure 1.
Mike Pearson provided a number  of animations for these two articles. The first one allows you to watch the numbers as they are chosen.  When it finishes it looks like the number 38 was chosen significantly more times than any other number. A second animations allows you to see gaps between each time a number is chosenYou will see that the longest gap observed is 72 for the number 17 which seems surprisingThe probability that a particular number would occur 72 times in a row is estimated to be about 1 in 12,5000.


[[Image:wallis1.png|500px|center]]
The article then goes on to discuss how finding these apparent surprises does not necessarily indicate that the numbers were non randomly chosen. For the number of times a number occurs the authors show that the distribution for the number of times a number a number should occur in n draws has a binomial distribution and then using the normal aproximation they obtain the following approximations for random choices suggesting that the having a number occur 38 times is not so suprising. 


<center> http://www.dartmouth.edu/~chance/forwiki/clt.jpg</center>


Discussion
They use a similar analysis to show that a gap of 72 is not too surprising. However, here they change the question.They calculate that in 1240 draws, each having 6 number, there are 7440 gaps that aspear. Then they ask:"What is the chance that the longest of these 7440 gaps is at lest 72". Using this they find there is about a 50% chance that a gap of at least 72 would appear. 


1. The article states, “The results of this study can be extrapolated to other white individuals (men and women) of North European origin.”  Find a biologist or a helpful librarian to determine whether it is suspected that non-whites have different telomere lengths and/or have a different distribution.  If so, what does this imply about telomere length and ageing?
Finally they discuss the use of a Chi Squared statistic to see if the approximate distributions from the data are consistent with the theoretical distributions used.
2. There were about nine times as many women in the study as men.  Why might this be a concern?
3. Something important is missing in Figure 1 and its absence serves to magnify the average difference.  What is it?
4. The subjects in the study were twins and therefore, attracted extra lay media attention.  Six of the ten authors are affiliated with Kings College, London.  From the Kings College website, “Comparing the telomere lengths of twins who were raised together but take different amounts of exercise, reduces the effect of genetic and environmental variation and so provides a more powerful test of the hypothesis.” Obtain the article and reference #21 to determine why twins as subjects as opposed to non-twins are sort of beside the point. 
5. There was a “discordant twin-pair analysis” performed “as a further confirmation of the larger analysis.”  A paired 2-tailed t test for 67 twin pairs, separated by at least a two category difference is displayed in Figure 2.  What defect does it share with Figure 1?  Why is it even more misleading given that a paired t test is being done? 
 
 
 
 
6. The article states, “A limitation of this type of study is that physical activity level was self-reported.”  Why might this be a limitation?
7. Assume there is a positive association between LTL and physical activity.  Give an alternative explanation to physical activity causing greater telomere length.  Give another alternative explanation.
 
Submitted by Paul Alper

Revision as of 00:04, 13 March 2008

dealt with what the British call League Tables but we would call rankings. David's first column appeared in Issue 44. Here David provides an example of a ranking where the outcomes should be pure chance but often do not look like pure chance. In his second column which appeared in Issue 45, David provides an example where the outcomes should be predoinantly skill also luck plays a role and he shows how to estimate how much of a role luck plays. In this the discussion is similar to our discussion of "Is poker a predominatly a game of skill or luck that we discussed in Chance News 29

In the UK National Lottery 6 numbers are randomly chosen from the numbers from 1 to 49. If you correctly predict the six numbers chosen you get a share of the jackpot.

Mike Pearson provided a number of animations for these two articles. The first one allows you to watch the numbers as they are chosen. When it finishes it looks like the number 38 was chosen significantly more times than any other number. A second animations allows you to see gaps between each time a number is chosen. You will see that the longest gap observed is 72 for the number 17 which seems surprising. The probability that a particular number would occur 72 times in a row is estimated to be about 1 in 12,5000.

The article then goes on to discuss how finding these apparent surprises does not necessarily indicate that the numbers were non randomly chosen. For the number of times a number occurs the authors show that the distribution for the number of times a number a number should occur in n draws has a binomial distribution and then using the normal aproximation they obtain the following approximations for random choices suggesting that the having a number occur 38 times is not so suprising.

http://www.dartmouth.edu/~chance/forwiki/clt.jpg

They use a similar analysis to show that a gap of 72 is not too surprising. However, here they change the question.They calculate that in 1240 draws, each having 6 number, there are 7440 gaps that aspear. Then they ask:"What is the chance that the longest of these 7440 gaps is at lest 72". Using this they find there is about a 50% chance that a gap of at least 72 would appear.

Finally they discuss the use of a Chi Squared statistic to see if the approximate distributions from the data are consistent with the theoretical distributions used.