Nature vs. Nurture - DNA and genetic predisposition

This is a bit off of my normal topics, however since a large portion of those who are undergoing autosomal testing are doing so for ancestry composition results or health results, I think it may be of interest to those who read my blog.

First, with a lot of the SNP's identified as increased risk if they are abnormal (polymorphic), it is important to actually look at what the studies tell you. Often it is only a slightly higher risk for a condition, such as some of the markers for gluten intolerance. Having an abnormal marker increases your risk of, but does not necessarily guarantee there is something wrong.

That said, I have a little bit of a rant on one subject. For those of you not scientifically inclined on DNA, SNP's are identified markers on our DNA. Those listed on the various health sites (such as livewello, 23andme, and promethease) have been studied. You can have one of three results on these markers. Normal, (having the normal markers), Heterozygous (one abnormal, one normal marker, means a mixed result) and homozygous (both abnormal). I hate to say Normal is good and homozygous is bad, because even if you are homozygous it doesn't always mean bad. But we tend to think in black and white, so then heterozygous is somewhat in between. Not good, not bad, but a mixture of the two.

There is a plethora of studies out there showing cardiovascular disease is in fact caused from inflammation, most specifically linked to elevated homocysteine levels. These elevated homocysteine levels come from the methylation cycle within our cells. Elevated homocysteine is also linked to Alzheimers and some cancers in research.

You may see something like the MTFHR gene mentioned by some who have done their DNA. It is one gene in the cycle of methylation that focuses on a cause for elevated homocysteine levels. This particular gene affects how our bodies metabolize folic acid. A person with a heterozygous result can metabolize some folic acid (in supplement not natural form). A person with a homozygous metabolizes very little folic acid (in supplement not natural form). It is important to note that estimations are around 40-50% of the population is heterozygous, and around 25% is homozygous for this gene.

However this is just one gene in a cycle that has several steps. The methylation cycle is one of the most important microbiological processes in our cells. By definition methylation is the process of a molecule bonding to a methyl group (a single carbon with 3 hydrogens attached). The methyl group changes the shape and function of that molecule and gives the molecule a new job. A pretty good explanation of it can be found here.

The later pathway of this cycle leads to the production of neurotransmitters (such as serotonin, dopamine, norepinephrine, and epinephrine).  One of the by products is homocysteine, which has gene markers also that have to do with how our body handles it. Homocysteine is a normal by product that the body breaks down when everything is working normally. It is elevated homocysteine levels that cause the inflammation and cellular breakdown linked to many diseases in research.

So what is my rant. Despite knowing inflammation causes heart disease, and despite questionable research on the problems with statins (can cause diabetes, can cause liver problems and not well researched for women. See more here. ) we haven't changed a thing about reducing the inflammation and the cause of the inflammation in our treatment.

Studies about MTFHR specifically have been published for at least 15 years. Yet nothing in healthcare in the United States addresses treatment for abnormalities in this cycle. If it's true as the nutrigenomic proposers state that you can negate some of the effects of these abnormal genes then why hasn't it been addressed? Is it because as a society our medical professionals look down on vitamin supplements as a cure? Is it because in the trend of health care we treat conditions with pathways that are not individualized to the patient?

Now I don't know for a fact, but I suspect many doctors would roll their eyes if someone took their DNA results with their abnormal markers in and asked them about it. It would be one up on the google doctor syndrome that they detest. However, unlike some of the other markers, this specific area, the effects of these genes has been studied pretty significantly, but health care providers aren't trained to interpret these results or offer solutions.

I don't believe that all diseases are strictly nature or strictly nurture. I do think that a little of both is pretty much in play for most conditions. Yet if we are as a profession encouraging patients to eat right, exercise and be proactive in their health, why would we ignore a potential pathway to improving their overall health throughout their lifetime?

DNA statistics part 2- Maternal side

Mom's DNA results are challenging. About 80 % of my ancestry results are paternal. Mom's grandmother was a first generation American and we don't have a lot of matches from those lines, same for her Choctaw side. That said she has clusters of matches for some groups.

Note: I share 50 percent of my DNA with my parents and my daughter. On Gedmatch that number varies in cM from 3549 for Mom, 3552 for Dad and 3581 for my daughter using my 23andme test. Dad and mom are both on 23andme and my daughter is on Ancestry. For an average I am using 3560 cM as marker for 50%.  Differences are likely due to unreadable (no call) areas from the samples.

Based on the unrealistic 50 % DNA from each parent in each generation, this is what the contributed DNA “should” be for my parents, me and my daughter if every generation was inherited equally at 25 % for each grandparent’s DNA contribution.

Relationship to my Mom/Dad	Percentage	Dad/Mom’s estimated cM	My estimated cM	My daughters estimated cM
Grandparent	25 %	1780 cM	890 cM	445 cM
Great Grandparent	12.5%	890 cM	445 cM	222.5 cM
G.G. grandparent	6.25%	445 cM	222.5 cM	111.3 cM
G.G.G. grandparent	3.125%	222.5 cM	111.3 cM	55.6 cM
GGGG grandparent	1.563 %	111.3 cM	55.6 cM	27.81 cM
GGGGG grandparent	0.781 %	55.6 cM	27.81 cM	13.9 cM

My parents are only on 23andme and Gedmatch, where I am on Ancestry, 23andme and Gedmatch and my daughter is on Ancestry and Gedmatch only. (I am not using FTDNA or my heritage matches for this table.)  Since most “in common” identified matches will go back to a common ancestor pair (or double the DNA from the above table as “possible”) I wanted to look at the highest match to a known DNA pair for my parents, myself and my daughter. 

Results for my mother’s family are below.

Surname Pair	Relationship to Mom	Mom’s estimated Cm	Mom’s highest match	My estimated Cm	My highest match	My daughters estimated Cm	My daughters highest match
Hager/Adams	Grandparents	3560	NA	1780	NA	890	NA
Hinds/Timmins	Grandparents	3560	2006.1 Aunt	1780	1229	890	609
Hager/Collins	G Grandparents	1780	590.6 ½ 1c	890	218	445	35.1
Adams/Trahern	G grandparents	1780	580.4 1C1R	890	232.5	445	91.8
Hinds/Paxton	G grandparents	1780	43.8	890	100	445	NA
Timmins/ Brampton	G grandparents	1780	300	890	175	445	NA
Hager/Barnett	GG grandparents	890	146	445	42	222.5	25.2
Collins/ Mangum	GG Grandparents	890	37.2	445	15	222.5	NA
Hinds/Crawford	GG grandparents	890	NA	445	28.4	222.5	11.2
Paxton/Douglas	GG grandparents	890	NA	445	NA	222.5	NA
Adams/Rogers	GG grandparents	890	NA	445	NA	222.5	NA
Trahern/ Gardner	GG grandparents	890	NA	445	NA	222.5	NA
Timmins/Phillips	GG grandparents	890	NA	445	NA	222.5	NA
Brampton/ Spicer	GG grandparents	890	NA	445	NA	222.5	NA
Hager/Whitley	GGG grandparents	445	NA	222.5	23.9	111.3	NA
Barnett/ Bagwell	GGG grandparents	445	97.3	222.5	NA	111.3	NA
Adams/ Unknown	GGG grandparents	445	NA	222.5	NA	111.3	NA
Rogers/ Rodgers	GGG grandparents	445	174	222.5	48	111.3	24.5
Trahern/ Hall	GGG grandparents	445	NA	222.5	N	111.3	NA
Gardner/ Unknown	GGG grandparents	445	NA	222.5	NA	111.3	NA
Collins/Adams	GGG grandparents	445	45.1	222.5	18.3	111.3	19.4
Mangum/ Unknown	GGG grandparents	445	NA	222.5	NA	111.3	NA
Hinds/ Bent	GGG grandparents	445	NA	222.5	28.3	111.3	NA
Crawford/ Wheeler	GGG grandparents	445	NA	222.5	NA	111.3	NA
Paxton/ Brown	GGG grandparents	445	NA	222.5	NA	111.3	NA
Douglas/ Unknown	GGG grandparents	445	NA	222.5	NA	111.3	NA
Timmins/ Hale	GGG grandparents	445	NA	222.5	NA	111.3	NA
Phillips/ Castle	GGG grandparents	445	NA	222.5	NA	111.3	NA
Brampton/ Unknown	GGG grandparents	445	NA	222.5	NA	111.3	NA
Spicer/ Haywood	GGG grandparents	445	NA	222.5	NA	111.3	NA