By DFK | February 05, 2013 at 06:36 PM EST |
15 comments
This is a previous post from last year, modified a bit to get everyone on the “same page”. With the many different people reading this blog, I thought it best to have a baseline with the discussions starting with the disease risk information. (Please note that this is generalized for folks who do not have a background with this information. Also, while the results presented below are from 23andMe, the rest of the information was taken from various sources.)
The human genome is made up of a sequence of four chemicals, called nucleotide bases, and includes adenine (A), guanine (G), thymine (T), and Cytosine(C). This sequence is our DNA and it is found in almost every cell of the body on 23 chromosomes. We get a set of chromosomes from each parent, so there are 46 chromosomes in each cell (23 pairs). The sequence of DNA from each parent is about three (3) billion bases long...the four chemicals in a long sequence. Based on DNA we are about 99.9% the same. Differences between individuals can be described as genetic variation. In some cases the genetic variation can be a result of a change in the sequence by one nucleotide base replacing another, such as an A replacing a G. For instance:
A sequence that is the most “common” sequence may be TCC AAG CTG GAA TCC GGT GTC
The variation may be: TCC AAG CAG GAA TCC GGT GTC, where A (adenine) replaced T (thymine).
This is called a single nucleotide change or single nucleotide polymorphism (SNP, pronounced “snip”), since one chemical replaced another. At a given point on each chromosome, there is a specific nucleotide base. Remember that each parent contributes 23 chromosomes, so there are two sets of chromosomes. At a given point on each chromosome is a nucleotide base from each parent. The pair of bases is called a genotype. A SNP can occur at a given point on the chromosome from either or both parents. The change(s) may result in a difference from one individual to another. We will have some examples of this over the coming weeks.
Disease Risk: The 23andMe information provides data about increased risk of disease, average risk of disease and decreased risk of disease. Here, the risk is a RELATIVE risk. Let’s start with increased risk of disease. According to 23andMe, JES has 1.54 times the average risk of getting rheumatoid arthritis (RA).
How was this information provided to JES? Through what is called the “odds calculator”, where 3.7 men with a genetic make-up like JESs’, according to 23andMe may develop RA where as with average risk 2.4 men out of 100 may develop the disease. The 1.54 times the average risk value is simply 3.7 divided by 2.4.
So what is the genetic basis for this increased relative risk of getting RA? There are eight SNPs (snips) that have been associated with the risk of RA, in individuals with a similar ancestry to JES. Below are JES’s genotypes for each of the eight SNPs related to RA:
SNP1 genotype TT; 1.95 times the average risk – increased risk
SNP2 genotype GG; 0.79 times the average risk (less than 1 means decreased risk) – decreased risk
SNP3 genotype CT; 0.92 times the average risk – decreased risk
SNP4 genotype AA; 0.93 times the average risk – decreased risk
SNP5 genotype AG; 0.97 times the average risk – decreased risk
SNP6 genotype GT; 1.13 times the average risk – increased risk
SNP7 genotype AA; 1.04 times the average risk – increased risk
SNP8 genotype GT; 1.03 times the average risk – increased risk
To put the above data into context, multiple large studies identified relationships between the specific SNPs and the risk of RA. Taking into account the SNPs that are related to increase risk, again relative risk of RA (numbers 1, 6, 7, and 8) and those that are related to decreased risk (numbers 2, 3, 4, and 5) result in an overall increased risk of 1.54 times the average overall risk. This data is based on information from individuals with a similar (European) ancestry to that of JES. Specifically the data comes from two studies including thousands of patients with RA and also thousands of “control” patients without the disease.
What does this mean to JES. Does this mean he will get RA?
Again, we have such a diverse audience reading this. I hope that the presentation of the information makes sense. There is a great deal of work that needs to be done to understand JES’s relative risk as presented in his data. Most individuals will look only at the summary data and not look at this technical level. Again risk does not mean it will happen. The genetic-based risk must be looked at in the context of overall risk that includes diet, and the environment among other potential risk factors.
What are your thoughts?
In my opinion, even though being at risk for RA does not mean that JES will develop the disease, it still helps tremendously for him to know his risk factor. There is no known prevention for RA, but proper early treatment can help prevent further joint damage for JES, in case he does get diagnosed with this autoimmune disease one day .
Just because JES is at a higher risk for RA does not mean he will actually develop the disease. As long has he keeps a healthy diet, regularly exercises, and follows the other necessary precautions, and should be able to avoid the odds. Having access to this information, JES can now take the precautions associated with RA and, if he does develop the disease, treat it early before further damage.
It's very important to understand that there is so much more that we have yet to understand as a community. So, as we can easily conceive now is that these findings with relations of genetics to risks, physical traits, etc are based on many factors other than shear genes. The idea is for the public to use this information in how they see fit, possibly improve healthy habits. And, as a benchmark for researchers to continue their studies to get closer to definite answers.
The risk of this disease is much more than thinking about simply the increase risk in front of the word RA. There are ways to help improve their overall health and even steps to treat the early onset of RA. While there may not be a known cure for RA we can use tests such as the one done to help give individuals at the very least a loose presentation of their risk to diseases such as RA. The researchers need to be careful to note that this study is not precise, and variables could be hidden that could change the test result.
I think that it is important to see the fact that JES is at increased risk for RA, as he may be able to better take care of himself so that he might avoid developing RA at all. Just because he has an increased risk, does not mean that he will have RA. It truly depends on whether or not the genes are actually expressed or not. Giving tests that present such information are helpful, as people can better tailor their focus on health depending on what different diseases the individual may be at increased risk for.
It is important for JES to know that there is an increased risk for him getting RA. Although the increased risk does not absolutely mean that that he will get the disease, it does show that he is more susceptible to getting RA. Just having a little increased risk should be something to be aware of. Taking into account the SNPs, it shows that there is a 50:50 ratio between the SNP with decreased risk and increased risk. However SNP1, has a 1.95 times the average risk. This is almost 2.00 times the average risk. If anything greater than 1 resembles increased risk, 2 is something that should be taken into consideration.
It is important that JES is aware of his increased risk for RA, but this does not mean that JES will get RA. There is currently no cure for RA but they could treat his symptoms early on and help ease pain. JES does have 2 times the average risk, so if there is any type of care he can do to delay onset, then it may be helpful.
If I knew I was at an increased risk of getting RA, like JES, I would do as much as possible to try and prevent the disease. Even though it is not definite that he will get the disease, my opinion is that is always better to know if you at an increased chance of getting a disease. I know preventative measures don't always work but it would be helpful to at least know that you have tried.
It seems that I agree with everyone who has posted so far about JES. I also think that he should look into maintaining an overall healthy life. What I find interesting is that the summary article on PubMed about RA states that women actually acquire the disease more often than men. I wonder then, if JES was female instead of male, if that would change how JES would respond to these results. Especially taking into account that by having RA you are at an increased risk of developing osteoporosis, heart problems, and lung disease.
JES can use the information to be aware if he begins to develop symptoms that seem like it might be RA that he does have an increased chance of getting the disease. I think this is a great example about how complicated the human genome is. JES has some SNPs that lower his risk of RA, but unfortunately the SNPs that increase his risk over comes these, in terms of the odds. In the future someone may discover other SNPs that play into the scenario which might change JES's odds, so that's something else he could keep in mind.
They say knowing is half the battle. With this information, JES may be able to notice early signs of RA and take steps to minimize his risk of permanent damage to his joints. Better to be aware and alert early than be blindsided later.
JES may have a more increased risk of being diagnosed with RA than the average male, but that does not necessarily mean that he will get it. What it does mean is that he is more likely to get it. Now that he knows that he does have an increased risk he can do things that will keep him or get him to a healthy lifestyle. Simply having physical activity every day can help decrease his odds a little, there are even studies that say UV-B rays from the sun can lower risks.
I would be interested to know if having this information does in fact change the way JES (or anyone who participates in genetic testing) approaches his life. After all, it is common knowledge that eating vegetables and exercising can prevent a myriad of diseases, but most studies indicate that the population at large is not necessarily loading up on broccoli at dinner, or trading cars for bicycles. We know that carrying extra pounds increases our risks for all sorts of illnesses, but there is little evidence that this knowledge has had any effect on the growing obesity problem our country is currently experiencing. Would the impact of a test showing your increased risk for a potential disease like RA really provide the impetus for sustained lifestyle changes?
The description sounds very good and easy to understand for me since I have some background knowledge about genome and protein. However, I believe that the information described can be hard for many people who doesn't know what protein means.
The increased risk of getting RA doesn't mean that you are going to get it as you said. Even with 1.54 times the increase risk from normal people, it is still 3.7/100. That minor difference can be affected by the environmental factors and the data can be changed when larger database is established. If I were JES, I wouldn't worry but rather have healthy habits to maintain good health.
Just because JES has an increased risk of developing RA does not mean that he will. It just states that he is more likely to develop it, not that it will happen for certain. Also, since JES knows that he has an increased risk for developing RA, he might be able to decrease his odds slightly by living a healthy and active lifestyle.