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?