Multiple Sclerosis and IBC

One of the news digest has my story

Multiple Sclerosis has many aspects.  Some items people do not want to talk about, such as constipation or Diarrhea.  My partner found a helpful solution, not to solve the ongoing problem, but one to help in the bathroom.

  Most Guys would never think of using a bidet, and think they are only made for women, and a special toilet bidet needed installed. This is not the case, and this gadget I have found to be one of the best.  It can be made for a man or woman. It can be heated, or unheated. Many versions.

This one hooks right up to your existing toilet.

Bathroom Luxury Meets Eco-Friendly

I was skeptical, but had mentioned one for my birthday to my Partner. A type of unexpected present for our home we call the Treehouse. This Winter I may be going WOW with cooler water!

A easy installation, and wonder why they are not being used everywhere.

It saves toilet paper, as all you are doing is patting  yourself dry.  We will have hand towels  next to the bathtub shortly for  just this purpose.

 since we live are remote, and on a well, and septic, this will help our system tremendously.

https://luxebidet.com/ref/JoeY/

I am always looking for answeres or help. 

Pathways to bowel or bladder dysfunction are common with Multiple Sclerosis. I read many blogs about this on  https://irritablebowelsyndrome.net the newest

https://irritablebowelsyndrome.net/living/wasted-time/

https://multiplesclerosis.net/living-with-ms/digestive-problems-diarrhea-embarrassing

https://multiplesclerosis.net/living-with-ms/digestive-problems-diarrhea-embarrassing

Yet another great link!

I did find Most Multiple Sclerosis people are low in Bile Production.

Thus the alternating constipation or Diarrhea

I found this government paper on 

Butyric acid in irritable bowel syndrome

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4027835/

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4027835/

"a group of short-chain fatty acids and is thought to play several beneficial roles in the gastrointestinal tract."

These symptoms people have cross over from Multiple Sclerosis to daily people. One report said one in six people live with IBS.  Sometimes caused by food we eat, or diets we try.

I am being a scientist with the help of a great GI Dr, his MD assistant, and a Wonderful Endocrinologist.

 I run a list of what I have found doing research on products. This is not something I would recommend anybody doing, without talking to their specialists.

Since being diagnosed with IBC-C, bowel problems run in the family from diverculitis, to bowel issues, and generation before me having some type of bowel issues.

My GI has me on Linzess, A powerful medication. That I use with lactulose 50-90 mil to provide relief. Simethicone is used for the Bloat. 

Ox Bile was tried, colon lining nutrition of calcium butyrate, magnesium butyrate, and butric acid.  Digestive support Pancreatin of Amylase, for carbohydrate digesting, protease, for protein digesting, and lipase, for fat digesting enzymes.  

Sodium Butyrate Bodybio.com had butric acid, which is a medium chain triglyceride MCT. It provided microbiome support, improved digestion, healthy metabolism.

Also on my regimine is Ceylon Cinnamon.Horbaach.com  It is known as the true cinnamon. Used for supporting healthy weight,  heart, circulatory, and joint health. Blood Sugars it also helps maintain.

My Heart Dr put me on Vascepa, Vascepa.com  for high Tryglicerides.  Berberine is also taken.

I take vitamin D.  People with MS are low in vitamin D, but have your blood work checked by a Endocrinologist before starting, and monitored.

I have a new list I went over with my specialist, some amino acids, some mushrooms, some minerals to help digestion, and restoration sleep. The Dangers of some supplements that contain Griffionia Simplicofola seeds known as Hydroxtryptophan or "5HTP", as serotonin overload syndrome can occur due to other MS medicine I am on.

A warning that all supplements are not the same, or some may be low quality, or not even have what is listed in it.  Wal-Mart, Walgreens, GNC all got in trouble years ago.

I try one at a time, make notes for few weeks. May try a combo that works better. Research the manufacture. I will have to make a second blog, on the next set of supplements, and which ones worked for me.

Let me know of ones I may be missing, or companies can send me a sample by emailing me for address

One of my stories was just published in irritablebowelsyndrom

https://irritablebowelsyndrome.net/stories/ibs-ms/

https://irritablebowelsyndrome.net/stories/ibs-ms/

Thanks for reading, stay safe.

JoeY

H63D/H63D genes and MS

 

https://youtu.be/rnKbImRPhTE?list=RDrnKbImRPhTE

For those who want the background music.

Multiple Sclerosis and having  H63D H63D  genes

Yes, A autoimmune story that requires a lot of research.

I find that I fall into the less than 5% that have the two copies of the H63D genes that cause Iron overload.  It began a few years back, when my endocrinologist was not obtaining lab results that she wanted.   I have been on Testosterone Therapy since the beginning of my multiple sclerosis

Most people with MS  have a deficiency of vitamin D, and also, Testosterone, and yet another one I found... Low Bile  Acids, which I will have to talk about later.

My Vitamin D was in ricketts stage when it was checked. I now stay in the #80's range, to be high for neurologist, but low enough not to get calcium in blood.

My pituitary Gland had a  MRI done. This meant I had to get off the real Biotin trial I was on for eight months, and give up Testosterone for six months. The Testosterone is hard to quit cold turkey.

But this still showed abnormal blood results, thus I was referred to the Cancer Clinic. The first Was, its caused by testosterone. I told him no, and he agreed for more testing. The first DNA, came back normal. 

 A Good GO, was my primary, and he mentioned the H633D Dna test. Right track, as that is what my cancer Dr ordered. The test came back with two mutated copies of the H63D gene, causing me have Haemochromatosis

17 phlebotomies, or for my UK readers, veins punctures to drain blood from me

It came out as thick as pancake batter.

Nord was joined. 

https://rarediseases.org/

I joined Rare Patients Voice

https://rarepatientvoice.com/

 in USA,  I had only found eight others with who had iron overload caused by the gene Mutation. They provide paid surveys for researchers, and anybody to join

I went back on my mothers side to a fourth grandparent and down that line, when a fith cousin responded. He was 74 years old, but Dr had him on blood thinners. His 23andme data showed the H63D gene. His Dr confirmed Haemochromatosis, and with the  double H63D gene. 

Now I know the one side of family link being passed on by generations. Do not know the other side, though. A Multiple Sclerosis Mystery also. Sanyogenetics.com Sanogenetics.com has my DNA, which has many MS genes it points to in a earlier blog.

H63D & S65C ~ The Forgotten HFE (Haemochromatosis) Mutations

Private group on Facebook was found earlier this year. 

https://m.facebook.com/groups/2309415149302702/

This led to a lot more research.

Checkiron.com

Youtube up to date info on CHECK IRON

Using this research tool, it allowed me to find another gene, The pro589Ser.

"Risk Score for HH Type 1 is 7.9

Coverage 42.46% for 23andMe

You are homozygous H63D which causes iron overload in 5.4% of cases but this is strongly increased by the Pro570Ser mutation.

H63D Two copies of H63D, 5.4% chance of iron overloadHFErs1049296(CT)3Pro570Ser - risk allele: T (Pro589Ser) This is called TF C2. It creates an increased likelihood of iron loading when combined with any c282y and h63d because it forces a reduced TIBC resulting in higher levels of free iron and free radicals. This also Increases susceptibility to Alzheimer's disease but only when combined with c282y."

My info, so I do not loose

http://checkiron.com/ci/resultsMV2.jsp?id=aeb2f92e034f413fa35f9e60d19ab533#home

http://checkiron.com/ci/resultsMV2.jsp?id=aeb2f92e034f413fa35f9e60d19ab533#home

Made for interesting research, as other genes were looked at. Wonder if they could add auto immune diseases, like find...  but Sanogenetics is covering this.

A find that my Endocrinologist thanked me for.

I Still have MS, with its daily tolls, and unknowns.  Botox was increased from 300 units to 500 units, trying to keep my spastic muscles that are overly stimulated by my MS. Many muscles In the calf and into the neck region. All guided by computer rhythm, but more by the professor neurologist that knows the name of each muscle, and what they control. I can feel when he hits the deep muscle that is hard as a rock.  This keeps me mobile with a cane.

https://rarepatientvoice.com/EverchangingMS/

Than you for reading. Hope some of these links will be helpful

JoeY

IBS and Multiple Sclerosis

IBS and MS

Yes, it hits kinda unexpectedly. First it was being plugged up. Bowles creating hard lumps that would not pass.  Generlac was prescribed eight years ago. A nother Dr, playing Dr did not know anything, and increased the Generlac to the point of having accidents at any given moment.

A test for Swallowing was done, by eating radio active food, and the Drs and entire staff watching how it slowly, and I mean slowly went from mouth to stomach.

Esophageal mobility disorder was given. Metoclopromide to help the muscles move food thru was also prescribed.  Apparently A drug used in many MS patients.

Then came

A upper and lower GI was performed. The Dr made it to believe I had Ulcerative colitis, when coming to. Yes, have them knock you out for this procedure.

Getting test results a few years later, besides the one they gave me was like pulling teeth. I received the Anesthesia report, which showed some problems they had.  I was to take VSL#3.

But since I started Bloating, a condition Kim Dolce describes quite well in her blog, 

https://multiplesclerosis.net/living-with-ms/irritable-bowel-syndrome/

I have gone thru all the test she has,  looking for small intestine overgrowth of bacteria,  a breath test to see how much methane I was producing. Could not pass a dui test haha..

  This is a part of your insides that starts inflating like a balloon. Yes, eight inches in diameter I would blow up. Think of Willy Wonka , Charlie and the chocolate factory. Their was this naughty girl, who insisted on chewing gum. And when it got to the blueberry flavor, she blew up like one.

 The difference is its only in the stomach, waist that swells up. If I could  prick the skin stretched so much with a pin, I would.

A different GI, I went to and a Smart GO, showed me why I did not have UC, but IBS.

That was a good thing, but what is the plan of action to take?

A article,

CAN HYDROCHLORIC ACID IMPROVE YOUR DIGESTIVE HEALTH? – ADVICE FROM DR. ROBERT MARSHALL, PHD

https://qnlabs.com/blog/can-hydrochloric-acid-improve-digestion-radio-show.html

This I have not tried yet. I see the GI every three months, so will ask.

I did a viome test to see foods on food map, to see my super foods, ones to avoid, and ones that were good. This perhaps pointed me in right direction of foods, but recommendations of other items my GI Dr questioned.  He sent me to a nutritionist to verify.

Things I have learned:

People with MS are low in Bile production.

Multiple sclerosis (MS) patients have lower than usual levels of molecules called bile acids circulating in their blood, a study found. These molecules, produced in the liver to aid fat absorption in the gut, also appear to block inflammation and nerve cell damage in the brain.Mar 31, 2020

https://multiplesclerosisnewstoday.com/news-posts/2020/03/31/bile-acid-supplements-may-ease-inflammation-symptoms-progressive-

little bit of research led me to an article published in the Oman Medical Journal. The study suggests patients with irritable bowel syndrome have a high rate of vitamin D deficiency.1 Another study published in the International Journal of Medicine found that patients with IBS who have low vitamin D serum levels showed an improvement in symptoms when treated with vitamin D therapy.2

I am on high dose of vitamin D,  being monitored by a endocrinologist, so knew this was not a problem with me, but others, may have a deficiency. Be monitored if taking high doses, as calcium build up could happen.

But this led me to add ox bile, and bile acids, along with a host of other supplements one at a time to see how my body reacted.

Some of what I have tried

Lactobacillus rhamnosus GG 5 billion cell

L-GLUTAMINE 500 mg Capsule

SODIUM BUTYRATE

PancreatinPANCREATIN-LIPASE-PROTEASE-AMY PO

Cinnamon 

BERBERINE-HERBAL

Magnesium

N-ACETYL-ALPHA-D-GLUCOSAMINE

Alpha lipoic acid

LACTOBACILLUS REUTERI PO

Vsl#3

Diets, did many.

Find most MS patients get a wrong signal telling muscles in intestines how to move. Metoclopromide  put on years ago for delayed emptying (slow moving from mouth down).

Esophageal mobility disorder.

Then tried many type of probiotic, even VSL#3, and then to pre biotics. List goes on. 

Apparently MS people are low in Bile acids also. So now on ox bile, and bile acids that break down fats, and carbs with a handful of other pills.

Chia seeds, flax meal, figs, psyllium husks, seeds, potato starch, benefiber, quinolla,  all tried

A tiny pill that has simethicone (Wal-Mart brand) has relief helps the bloating.

Still alternate, but linzess has been best, keeping me going (either liquid, soft, controlled by how much lactulose used)

 Always looking to find out what others use. 

 too much pressure from not the bloat, but from constipation can really cause damage.  The Bloat, quite uncomfortable. Puts 8 inches more On me.

Would love others experience, or what works.

Thank you for reading

JoeY

Pain Sensitivity...

Fight…. or flight!.  I know what my Pain Sensitivity is over the last eight years.

It was first tried to be controlled by Tramadol. A medicine I found to be allergic to the first week. Then came

Indomethacin.

One that burned holes in my stomach, so  prilosac, for the stomach, the It was opioids, and  morphine. Enough that the pharmacists thought I was giving it to someone on their death bed.

I was able to get off all these, except prilosac when a proper diagnosis came. Two meds work to block Pain in Multiple Sclerosis. Are Lyrica and Cymbalta combination. They need to start with name brands, as generics don't work. Gabbapentin is another good one. I am on over twenty five medicines, to control Pain and my multiple Sclerosis.  

A interesting report of DNA was done by Sanogenetics.com.  It shows some DNA they know is  related to Pain. Enclosed is their report, I find interesting.  Everyone has different Pain thresholds. I am sure DNA will shed light on many others.

https://palousemindfulness.com/MBSR/week0.html

Thanks for reading, and leave me a comment!

Joe

Pain Sensitivity

How does genetics influence the way we experience pain?

Pain Sensitivity

Complexity Level:Complex

low

Heritability- low -10%

Genetic variation in these sites has been associated with different levels of susceptibility to & risk of chronic pain.

HIGHER PAIN THRESHOLD

LOWER PAIN THRESHOLD

rs4680

AG

- This means that you are likely to have an intermediate pain threshold.

HIGHER RISK

LOWER RISK

rs1042713

GG

- This means you have a normal risk of experiencing chronic pain

Thermal pain

HIGHER THRESHOLD

LOWER THRESHOLD

rs25531

TT

- This means that you are likely to have a higher threshold for acute thermal pain.

A pulled muscle in the back or leg can send some of us to the couch for days whereas others seem to more easily recover. How can we explain differences in pain sensitivity and recovery? Could the answer be in our genes? Scientists have been studying the question for a long time and the answer is: “it’s complicated”. Susceptibility to pain appears to be dictated by interactions between your environment and your genetics.

Fight…. or flight!

Many of the genes found to be associated with pain sensitivity contribute to the production of adrenaline and serotonin .

Both adrenaline and serotonin are 'neurotransmitters', which act as messengers in the brain to carry information. Adrenaline is often known as one of the “stress hormones” and is responsible for the famous “fight or flight response”. Increased levels of adrenaline raise the heart rate, elevate blood pressure and boost energy supplies. In other words, adrenaline prepares the brain to react to immediate danger. In patients with chronic pain, some genetic variants have been found on a gene called COMT, which is known to be involved in the regulation of adrenaline. Genetic variation in the site called rs4680 has been associated with different levels of susceptibility to chronic pain. People with two G's in this position are much more tolerant to chronic pain!

SNP rs4680

You have the variant AG at position rs4680. This means that you are likely to have an intermediate pain threshold.

Genetic variation in another gene called ADRB2 also influences adrenaline levels and has also been suggested to play a role in pain sensation. One genetic variant near ADRB2 has been associated with chronic pain: rs1042713. Curiously, the adrenaline related genes mentioned in this article may also be associated with sleep dysfunction and anxiety.

SNP rs1042713

You have the variant GG at position rs1042713. This means you have a normal risk of experiencing chronic pain.

Pleasure or pain?

The second neurotransmitter system that seems affected in patients with chronic pain is the serotonin pathway. Serotonin is often prescribed as an anti-depressant and is popularly thought to contribute to feelings of well-being and happiness. This description does not do serotonin justice, as it does far more in our body than regulate emotions and works in complex and intricate ways. In the context of pain for example, serotonin can act as an analgesic (painkiller) or as hyperalgesic (pain enhancer), depending on where it acts in the body. Several genes controlling serotonin production are involved in susceptibility to pain. The HTR2A gene codes for a protein that acts as a 'landing pad' or receptor for serotonin. The serotonin transporter gene SLC6A4 is also involved in pain perception. If you have two C's at rs25531, you are more likely, on average, to be more sensitive to thermal pain (such burns or frost bites).

SNP rs25531

You have the variant TT at position rs25531. This means that you have a higher threshold for acute thermal pain.

This genetic variant was not included in your original DNA data file. During our upgrade process, we determined your most likely genotype at this position using imputation.

More about imputation

What does this tell us?

This is only a snapshot of the many genes that are involved in pain sensitivity. It is important not to forget that the perception of pain can also be influenced by psychological factors. A recent study suggested that swearing out loud while immersing your hand in cold water can help relieving the pain . Overall, more research is needed to truly understand the biological nature of pain. As our understanding improves, there may be opportunities to develop more personalised treatments to acute and chronic pain.

Image credit: - Unsplash

References

[1]The phenotypic and genetic signatures of common musculoskeletal pain conditions.

[2]The science of why swearing reduces pain.

Glossary

[SNP]

SNP stands for 'single nucleotide polymorphism' and refers to regions of DNA that vary between individuals.

SANO and Multiple Sclerosis a some of my DNA

Multiple Sclerosis

Complexity Level:Complex

mid

Heritability- medium -48% - 64%

Multiple Sclerosis (MS) is a rare autoimmune condition, caused by a body’s own immune system attacking its central nervous system.

A quick note: this article is not intended as diagnosis or treatment advice.

As well as the genes covered here, around 200 more have also been found to contribute to MS, along with environmental factors, so this is very far from being a full picture of your risk level.

i

Different variations in some of the HLA* family of genes and certain T-cell related genes have been found to relate to different levels of risk.

HIGHER RISK

LOWER RISK

rs3135388

TC

effect:3Higher risk

rs4959039

AG

effect:1.4Higher risk

rs6897932

CC

effect:1.08Higher risk

rs2104286

GA

effect:1.4Higher risk

*Read on for more detail on exactly how these genes and environmental factors like vitamin D deficiency affect MS risk.

This is my Data from SanoGenetics.com. Quite a interesting read. They picked up my Data from 23andme.com, so not a complete set of DNA used.  I have asked their permission to use this page in my blog,  as this information may help scientist and researchers.  Tellmegen.com has a  complete set of my DNA, along with Allofus.org

Vitamin D may also play a role in MS. A detailed report is available by emailing me, as I will retest to see if some items Tellmegen.com has shown interferes or not with vitamin D. 

JoeY
                     A song that I thought would fit this DNA from yester year

Time in a bottle plus the classic Sound of silence

TURKMENISTAN - WHY ARE THE STREETS SO EMPTY?

This report covers several of the genes known to play a role in Multiple Sclerosis (MS). This article is not intended as a diagnosis or to provide treatment advice, but as an educational and informational tool that is personalised to your genetic data. Beyond the genes covered here, there are around 200 genes which have been identified that also contribute to MS. Non-genetic factors such as Vitamin D also play a role in MS, and are explored in this report .

What is Multiple Sclerosis?

Multiple Sclerosis (MS) is a rare autoimmune condition which is caused by the body’s own immune system attacking its central nervous system .

It is characterized by a wide variety of symptoms including problems with vision, movement and speech .

The risk of developing MS is influenced by many factors including genetics. Several genes have been identified in influencing the development of MS, many of which regulate the immune system.

Which genes influence a person's possible development of Multiple Sclerosis?

The Human Leukocyte Antigen (HLA) is a family of MS related genes that make a group of proteins called the HLA complex which plays a role in helping immune cells communicate with each other. The HLA complex helps the immune system to differentiate between foreign attackers (e.g. bacteria or viruses) and the body's own tissues. In MS, the immune system is unable to distinguish between the body's own tissues and a foreign attacker due to a miscommunication between immune cells.

Different variations of HLA genes have been found to relate to the risk of developing MS. Two of those variations are HLA-DRB1 (rs3135388) and HLA-G (rs4959039). Allele rs3135388(T) in HLA-DRB1 has been associated with a 3 to 6-fold higher risk of developing MS.

SNP rs3135388

You have the variant TC at position rs3135388. You have about a 3 times higher risk, than the average person, of developing Multiple Sclerosis.

Allele rs4959039(G) in HLA-G has shown to be associated with around a 2-fold higher risk for developing MS.

SNP rs4959039

You have the variant AG at position rs4959039. You have about a 1.4 times higher risk, than the average person, of developing Multiple Sclerosis.

What environmental factors influence a person's chances of developing Multiple Sclerosis?

One of the environmental factors which has been linked to the development of MS is vitamin D deficiency. People with MS have lower levels of 25-hydroxyvitamin D3 (25-OHD3) in their bodies. Research suggests that increasing Vitamin D levels in people with a predisposition to developing MS may reduce risk of developing the condition.

In the kidney, skin and immune cells, 25-OHD3 is processed and activated by a gene called CYP27B1. This means that the final level of active vitamin D3 is dependent not just on Vitamin D levels, which is influenced by factors such as sun exposure and diet, but also genetic factors in the CYP27B1 gene.

Low levels of CYP27B1 will likely influence the available amount of active vitamin D3 present in the body. As a result, studies have shown that Individuals with allele rs703842 (T), which is correlated with lower levels of CYP27B1, are on average more likely to be affected by MS.

SNP rs703842

You have the variant TT at position rs703842. This variant is associated with an increased risk of developing Multiple Sclerosis.

What are T cells and what role do they play in developing Multiple Sclerosis?

The IL7RA gene produces a protein that participates in immune system response and in T cell (a type of immune cell) development. Some genetic variants in IL7RA result in decreased protein levels. It has been shown that carriers of the allele rs6897932 (C) produce less IL7RA, and people with allele rs6897932 (C;C) have about 2 fold higher risk for MS development. On the other hand, the (C;T) and (T;T) variants are associated with protection against MS.

SNP rs6897932

You have the variant CC at position rs6897932. This variant is associated with an 1.08 times higher risk, than the average person, of developing Multiple Sclerosis.

T Cells, mentioned previously, are an important part of our body's immune system and are involved in ‘adaptive immunity’, which includes a system for remembering past threats and responding to those threats when they occur again. MS, like many autoimmune diseases, is in part the result of T Cells not functioning correctly, and attacking the bodies own cells.

IL2RA produces a protein that is involved in T-Cell growth, and genetic variants in IL2RA are associated with MS risk. The rs2104286 (A) allele is associated with a higher risk of MS, while the rs2104286 (G;G) allele is associated with lower MS risk. One of the FDA-approved treatments for MS, daclizumab, works by blocking IL2RA.

In conclusion

There are around 200 genes which could influence a person’s development of Multiple Sclerosis, many of which regulate the immune system. Some genes may increase or decrease the risk of developing MS directly, whereas others may increase or decrease the risk of associated conditions such as vitamin D deficiency that can influence a person's likelihood of developing MS. However, genetics is just a small factor among many other factors (including environmental, immunologic and infectious factors) which influence a persons likelihood of developing MS.

Research into immunology, epidemiology, genetics and infectious agents is essential to increase our understanding of the causes of MS as well as helping to discover more effective treatments.

References

[1]National MS Society: What Causes MS?

[2]Mayo Clinic: Multiple Sclerosis

[3]Sano Genetics: Multiple Sclerosis

Glossary

[Environmental Factors]

Environmental factors are external influences that can affect an individual's health and wellbeing.

[Immune System]

The organs and processes of the body that provide resistance to infection and toxins.

[Immunological]

Relating to the structure and function of the immune system

[Infectious Agents]

Is generally used to describe and encompass any material that can cause an infection that can lead to a disease. There are four main classes of infectious agents: bacteria, viruses, fungi, and parasites.

[Protein]

Proteins are large, complex molecules that play many critical roles in the body.

[SNP]

SNP stands for 'single nucleotide polymorphism' and refers to regions of DNA that vary

Sano home

But even more DNA using  DNA from tellmegen.com

rs10492972       AG (or TC if reading the complementary DNA strand))                     G (or C) is the risk allele

KIF1B gene              conflicting reports; possible slight increased risk for multiple sclerosis

rs12722489     IL2RA gene    AG                   a slight increase in risk of developing multiple sclerosis      G is the risk allele

rs6498169        AG       KIAA0350 gene   1.14x risk of multiple sclerosis          A is the risk allele

rs10984447    AG        DBC1 gene        1.17x increased risk for multiple sclerosis    A is the risk allele

rs12044852   AC         CD58                  1.24X risk           C is the risk allele

rs12708716    AA       CLEC16A       1.6x risk of type-1 diabetes and other autoimmune diseases (such as MS)          A is the risk allele

rs4149584     GG        TNFRSF1A       normal risk           A is the risk allele

rs3135388     AG (or TC)      HLA-DRA          3x higher risk of multiple sclerosis                 A (or T) is the risk allele