Optimizing Health outcomes using mapped personal genome

I thought that it may an idea to try and set up a knowledge base of relevant Single Nucleotide Polymorphisms (SNP) that we can use to make informed decisions about how to optimise our possible health outcome.

This list would come in handy especially if one has their genome mapped with companies such as 23andme or Navigenics.

I thought of this when I recently read a post made by FunkOdyssey. It read

I'm using methylfolate on the off chance I have an MTHFR polymorphism

from wikipedia

There is a common DNA sequence variant (polymorphism) in MTHFR at basepair 677 (a change from a C to a T) that results in a thermolabile enzyme with decreased enzymatic activity. Ten percent of the North American population are homozygous for this polymorphism (the incidence is higher in Mediterranean countries and lower in African-Americans). Individuals of 677TT are predisposed to mild hyperhomocysteinemia (high blood homocysteine levels), because they have less MTHFR available to produce 5-methyltetrahydrofolate (which is used to decrease homocysteine). Low dietary intake of the vitamin folic acid can also cause mild hyperhomocysteinemia. This polymorphism and mild hyperhomocysteinemia are associated with neural tube defects in offspring, arterial and venous thrombosis, and cardiovascular disease. It is interesting to note that 677TT individuals are at a decreased risk for certain leukemias and colon cancer, but only when their dietary intake of folate is high. The MTHFR gene could be one of the factors of overall schizophrenia risk.^[1] Schizophrenic patients having the risk allele (T\T) show more deficiencies in executive function tasks.^[2]

So, the MTHFR enzyme metabolises folate into methylfolate. The absense of this enzyme, as seen with the MTHFR polymorphism, means that folate is not metabolised hence the decision made by Funk to supplement with L-methyfolate instead of folate is a very important one if he were homozygous for the MTHFR polymorphism like 10% of the north American population.

I think that having the ability to make decisions about maximising your health based on what your genes say is absolutely phenomenal. Therefore, I proposed that we create teh above mentioned knowledge based. This will surely come in handy and act as a greatr resources once we all have our genome mapped.

I'll start with a fairly common polymorpism that will help you decided whether you should pursue you goal to be an olympic power lifter

The ACTN3 gene.

from wiki...

ACTN3 is a gene that encodes a structural protein, alpha-actinin 3, associated with muscle fibers.

Fast twitch versus slow twitch muscle fibers
Skeletal muscle is composed of long cylindrical cells called muscle fibers. There are two types of muscle fibers, slow twitch or muscle contraction (type I) and fast twitch (type II). Slow twitch fibers are more efficient in using oxygen to generate energy whilst fast twitch fibers are less efficient. However, fast twitch fibers fire more rapidly and generate more force.

Muscle fiber composition in elite athletes
On average each person has an even percentage of each fiber type but Olympic sprinters tend to have around 80% fast twitch fibers. Conversely, Olympic marathon runners tend to have around 80% slow twitch. There is controversy whether training may alter the percentage of fiber type percentage over time therefore heredity or genetics should be considered as playing the greatest role.

ACTN3 in muscle fiber
Each muscle fiber is composed of long tubes called myofibrils which in turn are composed of filaments. There are two types of filaments: actin (thin filaments) and myosin (thick filaments) which are arranged in parallel. A muscle contraction involves these filaments sliding past each other.

Actin filaments are stabilized by actin binding proteins known as actinins of which there are two main types, type 2 and type 3. Each of these is encoded by a specific gene, ACTN2 and ACTN3 respectively.

ACTN2 is expressed in all skeletal muscle fibers whereas ACTN3 is expressed only in fast twitch fibers.

The rs1815739 mutation
A mutation (rs1815739) has been identified in the ACTN3 gene which results in a deficiency of alpha-actinin 3 in a significant proportion of the population. Based on ethnicity the deficiency is found in 20-50% of people. Generally, African Americans have the lowest incidence of the mutation whilst Asians have the highest. Scientists believe that variations in this gene evolved to accommodate the energy expenditure requirements of people in various parts of the world.

Studies have linked the fiber twitch type with ACTN3, i.e. fast twitch fiber abundant individuals carry the non-mutant gene version. Also, studies in elite athletes have shown that the ACTN3 gene may influence athletic performance. Whilst the non-mutant version of the gene is associated with sprint performance, the mutant version is associated with endurance.

Edited by zoolander, 06 June 2008 - 03:17 AM.

Great idea. Perhaps people could what they know here and then it could all be collated by someone.

Great idea. Perhaps people could what they know here and then it could all be collated by someone.

SNPedia is doing it. For example:

rs662799 prevents weight gain from high fat diets
[PMID 17211608] rs662799 -1131T>C in APOA5 is present in approximately 13% of this population, modulates the effect of fat intake on BMI and obesity risk in both men and women. Individuals with at least one C allele gained significantly less weight on a high fat diet than those homozygous for the T allele.

or

The MTHFR gene encodes the vitamin-dependent enzyme, methylenetetrahydrofolate reductase. Several conditions or defects caused by functionally impaired forms of the MTHFR protein can be improved through dietary supplementation by folate.

There are 3 common SNPs giving rise to MTHFR alleles:

* rs1801133, also known as A222V
* rs1801131, also known as E429A
* rs2274976, also known as R594Q

It is likely that there are numerous other variations that are much rarer. When the MTHFR genes of 564 individuals of diverse ethnicities were fully sequenced, in addition to the 3 common alleles mentioned above, 11 other nonsynonymous changes were found, each with a frequency under 1%. Four of these 11 rarer alleles affected enzyme function (as did A222V) based on tests in yeast, most of which could be fixed with higher folate supplementation (in yeast; this is not yet tested in humans). Since all five impaired alleles map to the N-terminal catalytic domain of the enzyme, it seems likely that additional SNPs causing nonsynonymous changes in this region could have similar effects.10.1073/pnas.0802813105


SNP rs1801133, A22V, is not thought to be a major risk factor for neural tube defects [PMID 17035141] except in certain populations. For example, Dutch and Irish populations indicate an increased risk for (T;T) carriers [PMID 10090889], but this same genotype (ie carriers of the thermolabile T allele) appears to have a protective effect in an Italian population studied [PMID 12111380].

[PMID 16672082] a SNP in MTHFR which affects Neural-tube defects (Birth defects)

How about stress:

Resilience to stress and emotional response can be predicted genetically
April 7, 2008.

The individual ability to deal with stress influences many day-to-day behaviors as well as mood and anxiety disorders. Stress is also a risk factor for other diseases including hypertension, heart disease and cancer. Scientists looked at a variation in the gene that encodes the protein Neuropeptide Y, which has an anxiolytic (stress reducing) effect in the brain. Using a sample of over 500 individuals they located a single variation that could predict the level of this protein. Using brain imaging techniques that examined brain activity following stressful responces, they found that the gene variation predicted the severity of the stress response (1).

The reference number for the SNP is RS16147.

(1) doi:10.1038/nature06858

How about stress:

Resilience to stress and emotional response can be predicted genetically
April 7, 2008.

The individual ability to deal with stress influences many day-to-day behaviors as well as mood and anxiety disorders. Stress is also a risk factor for other diseases including hypertension, heart disease and cancer. Scientists looked at a variation in the gene that encodes the protein Neuropeptide Y, which has an anxiolytic (stress reducing) effect in the brain. Using a sample of over 500 individuals they located a single variation that could predict the level of this protein. Using brain imaging techniques that examined brain activity following stressful responces, they found that the gene variation predicted the severity of the stress response (1).

The reference number for the SNP is RS16147.

(1) doi:10.1038/nature06858

from SNPedia:

Rs16147 [PMID 18385673] located in the promoter region alters NPY expression in vitro and seems to account for more than half of the variation in expression in vivo. These convergent findings are consistent with the function of NPY as an anxiolytic peptide and help to explain inter-individual variation in resiliency to stress, a risk factor for many diseases.
Gene NPY
Chromosome 7
Position 24289935

plus links to several references to it

ilanso I understand the point your attempting to drive home i.e that SNPedia has all the information, but people are free to drop information on particular SNP's of interest to them and SNP's that they think would be important with health promotion/life-extension.

Importantly though, this thread has space for discussion. SNPedia is a database of information as far as I know