Tuesday, November 21, 2017

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?


Tuesday, October 31, 2017

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