An Introduction to the Genetics of Rheumatoid Arthritis (RA)

RA Genetics 101: Glass half-full or half-empty? Part 1

DNA imagePlease welcome Professor Robert W. West, Jr, PhD as a guest on the subject of Rheumatoid Arthritis and genetics. Professor West uses his expertise in genetics to teach Personalized Medicine and other courses to the doctors of the 21st Century. A recent article on Ankylosing Spondylitis (AS) illustrates how vital it will be for Rheumatoid Arthritis patients and researchers to become more invested in establishing the genetics of rheumatological diseases like AS and RA. Why are symptoms and treatment responses so varied? Will we find a cure? Genetics holds some of the keys.

Why write a guest post on the genetics of RA? I am a geneticist and molecular biologist by training and also a friend of Kelly’s. My connection to Kelly is two-fold: we are both staunch patient advocates aka e-Patients and we are “partners in pain” along with along with numerous others in the Twitter #rheum community. Either alone would suffice to establish a connection, but combined they become a powerful incentive to collaborate in a national effort to improve the treatment of chronic disease. While I personally have not been diagnosed with RA (more on my perspective of the complications of diagnosis later), I’ve discovered that RA patients have an acute appreciation for the disabling aspects of chronic pain, so we speak a common language that most others simply don’t understand.

I first ran into Kelly in mid-2010 on Twitter, during one of my early exposures to the #hcsm Tweetchat. This is a gathering of docs, RN’s, e-Patients, hospital staff, and others using social media to improving healthcare. It’s a great place to find out what’s going on in the healthcare community at large, and especially to meet folks who know much more than you about topics you’re interested in. Kelly’s participation in #hcsm is where it became clear to me, upon a bit of further investigation, she was an empowered patient in a league of her own, and I felt this provided a second common language between us.

Why study Rheumatoid Arthritis and genetics?

My goal for writing this series of posts is to facilitate the empowerment of both docs and patients to improve clinical care through modern approaches such as genetics, genomics, and bioinformatic methods established by the completion of the human genome project (HGP).  Since I also teach advanced electives in personalized medicine to medical students as an Associate Professor at SUNY Upstate Medical University, information presented here illustrates the approach I personally use to train the next generation of physicians. I believe we are establishing a model for how healthcare should be taught and practiced in the 21st century.

Being trained in genetics, it’s only second nature to attempt to explain the etiology of disease, RA in this case, via genetic contributions, with the ultimate purpose of connecting genotype (genetic variation) with phenotype (disease symptoms). Of course, if the respective genes involved are known, and corresponding proteins and biochemical pathways thus identified, then research scientists and doctors can determine where and how to focus potential therapies (e.g. drug targets).

How could a person find out about his genes with respect to RA?

Like 100,000 others, I have been genotyped by the “direct to consumer” (DTC) genetic testing company 23andMe. Conveniently, as part of their genotyping service they already provide an analysis of, nine genes or loci which have been shown to affect lifetime risk for RA. Locus is a term used to identify a chromosomal location whose proper “gene” has not yet been identified.

This provides a quick “foot in the door” to investigate the potential promise of genetic approaches to understanding and treating RA. In part 2 of this series, I present my own results from genotyping analysis provided by 23andMe specifically with respect to RA. In subsequent posts, I will discuss the present limitations of a genetic analysis such as this, and delve into the intricate details of determining the genetic and biochemical etiology of a common, polygenic disease like RA. By the end of this series, you will see that while genetic approaches offer promise in diagnosis and treatment of this devastating disease (really, “diseases”), the glass is only half full, or half-empty depending on your personal perspective, with respect to bona-fide clinical utility.

Stay tuned for part 2 of Rheumatoid Arthritis (RA) Genetics 101: Glass half-full or half-empty?

Nevertheless, I am particularly optimistic because a glass half-full is far better than one fully-empty.  Importantly, much of what I will discuss in terms of genetic approaches to understanding and treating RA would likewise apply to many other common, polygenic diseases such as asthma, which I happen to have myself.

Edit 7/23/11:

Part 2 of our RA & genetics series: Direct to Consumer Genetics of Rheumatoid Arthritis (RA)

Recommended reading

Kelly Young

Kelly Young is an advocate providing ways for patients to be better informed and have a greater voice in their healthcare. She is the president of the Rheumatoid Patient Foundation. Kelly received national acknowledgement with the 2011 WebMD Health Hero award. Through her writing, speaking, and use of social media, she is building a more accurate awareness of Rheumatoid disease aka Rheumatoid Arthritis (RA) geared toward the public and medical community; creating ways to empower patients to advocate for improved diagnosis and treatment; and bringing recognition and visibility to the Rheumatoid patient journey. In 2009, Kelly created Rheumatoid Arthritis Warrior, a comprehensive website about RA of about 950 pages and writes periodically for other newsletters and websites. Kelly served on the Mayo Clinic Center for Social Media Advisory Board. There are over 42,000 connections of her highly interactive Facebook Fan page. She created the hashtag: #rheum. Kelly is the mother of five, a home-schooler, Bible teacher, NASA enthusiast, and NFL fan. You can also connect with Kelly by on Twitter or YouTube, or LinkedIn. She has lived over nine years with unrelenting Rheumatoid disease. See also http://www.rawarrior.com/kelly-young-press/

19 thoughts on “An Introduction to the Genetics of Rheumatoid Arthritis (RA)

  • July 21, 2011 at 12:14 am
    Permalink

    This is the future. It is also why we need more funding for research. Thank you for bringing this here.

    Reply
  • July 21, 2011 at 1:29 am
    Permalink

    and “I’ve discovered that RA patients have an acute appreciation for the disabling aspects of chronic pain, so we speak a common language that most others simply don’t understand. ”

    A wonderful comment that so many can relate to. The aspects of pain on the mentality and social economics of our society have gone unnoticed for so long the damage and cost is uncomprehending

    Reply
  • July 21, 2011 at 7:40 am
    Permalink

    Thank you, Professor West. With my adult daughter and I both diagnosed with autoimmune disorders (me, RA, and her, probable RA) within months of each other, I look forward to the series with special interest. Thank you, Kelly, for making the series possible.

    Reply
  • July 21, 2011 at 9:32 am
    Permalink

    Defiantly something I’m interested in. With myself, my daughter and a first cousin all having RA I strongly believe there is a genetic link. I also have a sister with Hashimoto’s who is showing some symptoms of arthritis. RA maybe?

    Reply
  • July 21, 2011 at 9:56 am
    Permalink

    Wow! I’ve been following the discussion of the genetic links to RA for a while, and am eager to hear more of Dr. West’s information. Thank you, Kelly, for inviting him to be a guest blogger!

    Reply
  • July 21, 2011 at 10:47 am
    Permalink

    I think this is a very interesting article, however there is a little too much advertising going on so I had to dig deeper. To keep it balanced I have a quite recent news article in regards to home kit genetic testing. Here is the link: http://abcnews.go.com/Health/Wellness/consumer-dna-testing-notch/story?id=11227092 I’m not out to slam anyone here. I think what 23andMe does MAY be the beginning of what can potentially be a very good thing for all of us. For me though, it would be important that information on my own genetic testing would be more precise. I do not have the education that seems to be required in interpreting this kind of testing and needless worry is certainly something I don’t want when I already have RA to deal with.

    Reply
  • July 21, 2011 at 10:50 am
    Permalink

    Correction, the article was a year old (apparently I still think it’s 2010!).

    Reply
  • July 21, 2011 at 11:10 am
    Permalink

    My grandmother had horrible arthritis in her feet – swelling, redness, distortion and fatigue. She pushed herself to the ultimate taking care of Momma and me. Momma was diagnosed with RA in 1963 or 1964. I was in nursing school and ended up helping with her care during the first few years. After I married, my husband was transferred (Air Force) to Utah, where we spent the next 4 years. We were able to visit back east twice during that time. Each time Momma was worse and worse. She had had to quit work. She had had to get a wheelchair, finally, she had had to have a series of “sitters” be with her 24/7. When we returned from Utah, she put herself and her Momma (who couldn’t walk by that time) into a nursing home. I couldn’t take care of her, what with working, caring for 3 children under 6, and helping my husband work on his PhD.

    Now, years after Grandmomma’s death and Momma’s death, I have RA. Not as badly as Momma did, but severe enough. I’m sure there is a strong genetic link – and I can’t help worrying about my children and grandchildren. Will they develop it? Will there be help for them if they do?

    And, for myself, I worry – what will happen to me? My husband had another heart attack last week. He was in hospital 4 days with 2 cardiac caths – one for angioplasty of one artery, and the second to stent another artery. I’m still exhausted and in flare from the strain and all the going back and forth to the hospital.

    If I didn’t have RA I could work full time – even at nearly 70 – and have better insurance for him. Just DRAT! And to think my descendants may have to fight this awful disease. I feel like it’s my fault for somehow not knowing there would be a genetic component in this and for having children to begin with.

    Thank you, Professor West, for this discussion. I look forward to future posts. And thank you, Kelly, for inviting him to post here. This is information we need, and may lead to prevention and cures for future generations.
    Cheerio!
    Elizabeth

    Reply
    • July 22, 2011 at 1:35 pm
      Permalink

      Turtlemom,
      Sorry to hear about your lengthy family history of RA. IMO, your children are at increased risk and you may want to consider genetic testing for yourself and them, though there are no guarantees of nailing down a Dx this way. Disclaimer- I am not a clinician nor Certified Genetic Counselor so cannot provide official recommendations.

      Re: “I feel like it’s my fault for somehow not knowing there would be a genetic component in this and for having children to begin with.” All Docs should be well-versed in the significance of family history in disease, and hopefully your Doc(s) picked up on that immediately with respect to your family history of RA and its potential implications for your progeny. As far as genetic testing for common genetic diseases (e.g. RA) goes, however, that’s only been available over the past few years, so there’s nothing your Docs could have done about that before now. Here at SUNY Upstate Med, we now train Docs in genetic testing and personalized medicine, so that the next generation of clinicians will be aware of these new genetic tools to facilitate Dx and Tx. As far as “for having children to begin with”, you are entering into an extremely complex and uncharted territory that is also very personalized, and beyond the nature and intent of this blog post series. Maybe down the road…

      -Bob

      Reply
  • July 21, 2011 at 11:32 am
    Permalink

    Thank you, Kelly and Dr. West!! I look forward to reading the rest of this series. Though I don’t know much on the subject, I’ve always found genetics to be particularly intriguing…and would love to hear what Dr. West has learned! I definitely feel like this is the key to understanding these types of diseases, which will ultimately allow for better treatments and ::crosses fingers:: cures.

    Reply
  • July 21, 2011 at 2:36 pm
    Permalink

    My mother had/has ra, which has remained fairly mild and she has not treated since it’s onset when she was 16. My paternal grandfather was crippled quickly by an aggressive form when he was in his forties–his sister had it more mildly, and other siblings also suffered from type 1 diabetes and ms. My onset was sudden and severe at 38, and my oldest daughter was diagnosed with a milder juvenile arthritis at 17. All my children, a nephew, 2 nieces and both sisters are also celiac. We are a hot mess of autoimmune disease–genetics is indeed the key. I wish I had a stronger science background as it takes me a very long time to reach even a limited understanding of the genetic factors involved for all of us.

    Reply
    • July 21, 2011 at 2:44 pm
      Permalink

      I hope these posts written for lay people (with pictures and charts) will help all of us to begin to understand how the genetic factors relate to that search for answers. Your family seems to be one that would be good to study!

      Reply
    • July 23, 2011 at 11:32 am
      Permalink

      theladyinpred,
      Agree with Kelly, what an intriguing FH! I think subsequent posts I will provide (posts 4 & 5, in prep) will speak to you specific situation, more so than these earlier posts. They deal with the complexity of autoimmune diseases in general (and the hazards of DNA testing in general), including cross-talk between different autoimmune diseases and the respective difficulty of Dx and therefore Tx.

      -Bob

      Reply
  • July 21, 2011 at 9:41 pm
    Permalink

    My genetic profile at 23andme suggests I am low risk for RA. However when I was a grad student at Stanford and under a lot of stress (2 kids, single parenting, jobs, dissertation), I developed severe and crippling RA. (diagnosed first at student health and then they passed me on to specialists who confirmed.) My hands were in the claw position and I could not hold anything in them. My hips were in such pain that I could only get down the steps on my butt. I had overwhelming fatigue.
    Luckily I ignored my Stanford doctors who wanted to put me on steroids (they did not like this at all), researched RA at the med school library at Stanford (journals and texts) and then visited as many Bay Area health food stores as I could. (This was pre-internet). Doing this allowed me to design my own protocol (first, ditch meat as a pro-inflammatory agent) and by following my protocol I was pain free within a year.
    The genetic tests are suggestive, not predictive. I have had several other auto-immune illnesses that my genes suggest I will not have. But my genes weren’t reading themselves. They were listening to the higher call of environment and epigenetics.
    As long as it is understood that with very few exceptions, gene/environment interaction rules, 23andme and others are extraordinarily interesting on many levels and I highly recommend it.
    BTW, if I were to design a protocol today it would not be the same as before (with the exception of diet), today it would be low dose naltrexone all the way. The number of M.D.’s remarking on their patients with RA who improved dramatically and unexpectedly with ldn for other autoimmune illness (Crohn’s cancer, fibromyalgia, IBS, etc) is surprising even to me. I used it for one issue and voila – one month later my psoriasis was gone. I was not expecting that. You people do recommend ldn don’t you? If not, it is time. It normalizes the immune system which is why it works on so much. Not snake oil, just the power and depth and breadth of the immune system being shown.

    Reply
  • July 22, 2011 at 3:41 am
    Permalink

    Looking forward to this series of posts about RA (autoimmune disease) & genetics. Thanks, Prof. West & Kelly for bringing this here… 🙂

    God bless!

    Reply
  • July 22, 2011 at 8:27 am
    Permalink

    Much of what I have read indicates that while researchers have found a genetic component to the development of RA there also seems to be an environmental trigger of some sort required. They have long suspected a virus or infection of some sort but have been unable to find the offender. The thought process is that you have the genetic predisposition and then are exposed to some trigger or triggers which set the immune system into overdrive.

    The genetic link is undisputed but it is certainly interesting that your genetic risk is so low given that you have the disease. I think it would be nice if we had some clue what those triggers were. Smoking increases your risk, but aside from that, they’ve got nothing there.

    On the genetic side, I developed symptoms hard and fast in Sept. of 2009, was diagnosed in Nov. 2010. I am 57 and seronegative. My daughter, who just turned 37, developed Raynauds, and had some unexplained symptoms, neck stiffness, knee pain. Her Dr. ran some bloodwork and sent her to a rheumatologist – her Rf and anti-CCP are through the roof – she has RA. And even though her symptoms at this point are very mild, because of the numbers in her bloodwork, they are very concerned, and are starting treatment ASAP.

    Yea, genetics.

    Reply
  • July 22, 2011 at 11:51 am
    Permalink

    Thank you Dr. West for this interesting post.
    In my case, there is little doubt that genetics plays a strong role in RA and other forms of autoimmune arthritis. I had always known that the women in my family have severe arthritis. I never focused on the type of arthritis until I developed RA almost two years ago. I am very fortunate that my grandmother is still living, and I have since been able to speak to her in depth about the history of arthritis in our family. As it turns out, my grandmother, aunts and great grandmother all suffer from some form of autoimmune arthritis ranging from RA to PsA to AS. They are from a semi rural area with little or no access to specialized rheumatology care, so their issues were always generically labeled as “arthritis”.

    Reply
  • July 22, 2011 at 12:26 pm
    Permalink

    Leslie,
    Thanks for your comments. Your first paragraph was right on the money. In your second paragraph, however, I must correct your assumption that I myself have RA. I do not, at least that I am aware of. I have not received a diagnosis of such. I do have some of physical symptoms that appear to overlap those who have received an official Dx of RA, though my present diagnosis (for whatever its worth) is spinal stenosis and spinal myelopathy, and I’ve had two back surgeries in an attempt to treat. So, for example, in the second paragraph of this guest post (main page) where I state: “While I personally have not been diagnosed with RA (more on my perspective of the complications of diagnosis later),…”, this was meant to imply that while I do not officially have a Dx of RA (6 years ago I my #Rheum Dx was seronegative), I have not yet ruled out this possibility in spite of not having an official clinician’s Dx. Why? Because of the complexity of autoimmune diseases in particular, and clinical Dx in general. I deal with this complexity in detail (and length) in a subsequent post. Nevertheless, thanks for your comments. It’s clear you have considerable appreciation for the fundamentals of chronic disease processes, particularly genetic aspects.
    Sorry to hear about your family history of RA. Seems to be a common thread among those weighing-in here in the comments section…
    -Bob

    Reply

Leave a Reply

Your email address will not be published. Required fields are marked *

“imaware™

    Welcome to RA Warrior!

    Welcome

    Thanks for visiting this unique site full of information and encouragement to fight Rheumatoid Disease. You'll find hope, humor, and a helpful online community. I'm Kelly & I'll be glad to show you around if you'll click right here.

    Advertisement

    View more gifts at Zazzle.

    Let's Pin Together!

Would You Like Free Email Updates?
Stay in touch with RA Warrior.
We respect your privacy. Your email address will never be shared.