Genetics – Fibromyalgia Suspect #1

Dr. Pellegrino is a leading fibromyalgia specialist and author who has had FM himself since childhood. His observations of familial fibromyalgia patterns and permutations such as "the aging threshold" reflect more than 20 years' experience treating patients at the Ohio Pain & Rehab Specialists Center. Basic knowledge to help genomic researchers sort things out as we move closer to understanding and control.



All of us involved in fibromyalgia, either by treating it or having it, have come to appreciate how complicated this condition is…. Most important, there is more than one way to get fibromyalgia; it is an “end point” condition with multiple ways leading to it.

One of my pet peeves is that I continue to read in the scientific literature statements such as “the cause of fibromyalgia is not currently known,” or "future research will hopefully discover the cause of biromyalgia." This implies that we don't know anything about the causes. I have had some doctors and attorneys suggest to me that if the cause is unknown, then perhaps we are not even sure that fibromyalgia exists.

I think we can say that a number of causes of fibromyalgia are known at the present time. And I think one of our problems is that we try to be too scientific, when we really need to be more practical and logical. One difficulty is determining the difference between cause and pathological mechanism. In fibromyalgia the cause would be WHY fibromyalgia developed. The pathologic mechanism would be HOW fibromyalgia developed.

I have compiled a list of probable causes of fibromyalgia.

This list is based on my experiences and understanding of the current literature. My opinions on these probable causes may not be shared by everyone. My list of probable causes is as follows:

1. Genetics
2. Trauma
3. connective tissue disease
4. Infection
5. Catastrophic stresses
6. Chemical exposure.

Probable FM Cause #1: GENETICS

These observations support the notion that fibromyalgia can be inherited, or at least the tendency to develop fibromyalgia is inherited:

• Physicians who see patients with fibromyalgia can recall a number of patients who are relatives.

• I have seen numerous family members,mother-daughter, sister-sister, sister-brother, etc., who have the typical symptoms and findings of fibromyalgia.

• Several members of my family have fibromyalgia through four generations!

• I also see numerous patients who tell me they have family members known to have it (their family history is positive for fibromyalgia).

• Many adult patients state they had pain as a child.

Several studies on the hereditary aspects of fibromyalgia have been published. Dr. George Waylonis and I published a study in 1989.(1)

We studied 17 families and as many first-degree relatives as we could gather up (sibling, parent, child), and concluded that:

• A number of family members had fibromyalgia in a pattern that suggested an autosomal dominant mode of inheritance. This means that if one parent has fibromyalgia, then 50% of the offspring have a chance of getting fibromyalgia, whether they are male or female. 

• There also appeared to be a variable latent stage, which means that the fibromyalgia could develop at different ages in different offspring.

• There also appeared to be variable transmission (i.e., it could skip a generation).

My study found a high percentage of fibromyalgia in men with a positive family history, nearly equal to the women.

This is much different than the people who present to the doctor’s office, because among these people more than six times as many women as men will be diagnosed with Fibromyalgia. Men DO have Fibromyalgia, but they take a different course than women. Sometimes we have to go out and look for them because they do not tend to come to us to be diagnosed.

Dr. Dan Buskila from Israel performed a study looking at 60 children of 21 mothers with fibromyalgia.(2)

He found that 23% of the offspring, most of them female, have fibromyalgia. When he looked at the males with fibromyalgia, he found that the ones who were under 18 had fibromyalgia almost as frequently as the women under 18. He concluded that fibromyalgia had a major genetic component that possibly fit the autosomal dominant mode of inheritance (50% of children who have one parent with FM will have FM, whether male or female) – especially among males and females under age 18.

Dr. Buskila did another study looking at people with fibromyalgia, and many of their relatives.(3) He found that 45% of the relatives reported widespread musculoskeletal pain resembling fibromyalgia.

Other studies have supported an inherited pattern to fibromyalgia.

Dr. Muhammad Yunus performed Human Leukocyte Antigen (HLA) studies in fibromyalgia. HLAs are genetically determined molecules that are found in virtually all cells. HLA genes can be markers for certain diseases, and the results of Dr. Yunus’ HLA study suggests a genetic role in fibromyalgia.(4)

I believe that the literature, combined with accumulated clinical experience, supports a genetic cause of fibromyalgia.

A “common sense” approach would be to recognize that fibromyalgia is so common in the general population of the entire world that there must be some type of common genetic make-up that leads to it. Another logical conclusion from all of the available information is that people are genetically predisposed to getting fibromyalgia.

I think a number of people are programmed genetically to develop fibromyalgia over time, probably independent of the environment. However, for a number of others, an environmental trigger must occur (i.e., the other causes listed here and perhaps others yet unknown) for the fibromyalgia to develop.

Who Is at Risk Genetically to Develop Fibromyalgia?

I think the following can be considered at risk:

1. A child with one or both parents with fibromyalgia.

2. A child of one or both parents with a connective tissue disorder such as rheumatoid arthritis or lupus.

3. A child with a sibling who has fibromyalgia.

4. A child with a first-degree relative (parent or sibling) who has fibromyalgia.

Just because someone is a risk does not mean he or she will automatically get fibromyalgia. The right “trigger” may never happen. If a child at risk does become symptomatic with fibromyalgia, there’s a lot that can be done. (See
"Fibromyalgia in Children and Teens – Risk Factors, Symptoms, and Treatment"). Don’t assume that someone will get fibromyalgia or that it will be bad if he or she does.

Genetics Play a Role in Pain Sensitivity

Dr. George Uhl (a neurologist at Johns Hopkins) found that differences in pain perception were due to variations on the surface of nerve cells, specifically on the molecule called the mu opiate receptor. The mu receptor works by bonding with natural chemicals called peptides that help diminish the sensation of  pain. Individuals who have lots of these receptors (too few mu’s!) cannot diminish the pain as well, and even small stimuli can cause severe pain.

The number of these receptors is controlled by the action of the mu opiate receptor gene. Those with fibromyalgia, or at risk for it, may be genetically mu deficient.

I believe with additional research we will be able to further clarify specific genes causing pain, identify gene expression profiles of specific subtypes of fibromyalgia, and develop genetic-specific medicines to control pain and reduce the effects of fibromyalgia.

[Note: just weeks ago, a pioneering study involving whole genome sequencing of identical twins with a rare condition found that they had inherited a "double dose" of such a gene variant, one from each parent; a "dramatic manifestation" of what in single copies the researchers believe may explain a recognized pattern of fibromyalgia symptoms among other family members.(5)]

Genetics and the “Aging Threshold”

A common story I hear from patients is that their pains gradually developed without any obvious or precipitating event. We mentioned earlier that genetics may cause some people’s fibromyalgia to develop randomly at some point, and once the pain starts it’s always there and can get worse over time. But is this process random, programmed, or subject to environmental factors? Probably a combination is involved.

I see many children and teenagers with fibromyalgia, but I see more adults in their 30’s or older when they first developed fibromyalgia symptoms. If genetics were the only factor in developing fibromyalgia, I would expect more younger patients with chronic pain complaints.

Genetic expression of a condition may take years to happen, so some people who first develop FM symptoms in their 30’s or later may have programmed genes causing the delayed expression.

Although genetics are a factor, I think there might be additional factors causing the “delayed” development of fibromyalgia; factors that I refer to as the “aging threshold.”

The aging threshold implies that as a person gets older, the threshold is lower for developing fibromyalgia. The person may be more vulnerable to getting fibromyalgia from various causes in the [probable cause list], but the aging process is also a risk for getting fibromyalgia, especially in women.

Both men and women are found to lose their ability to inhibit chronic pain signals as they get older, and normal women already have a “defective” pain inhibitory system to begin with. Thus, any vulnerable person (who inherited fibromyalgia genes) would be less able to inhibit pain signals as he or she aged, and would become more susceptible to developing amplified pain (women more than men).

Also, wear and tear changes on the body over time may contribute to the aging threshold. As we age, inevitably our muscles, tendons, ligaments, discs and joints show signs of deterioration accumulated micro-trauma. These deteriorating tissues may form painful areas, i.e., pain-generation. In a vulnerable person, the development of painful areas may trigger the “amplified pain” cascade.

Additionally, hormonal changes over time can increase the risk for developing pain. For example, early menopausal women are more likely to report increased fibromyalgia pain.

If we combine these different factors, we can appreciate how the pain / fibromyalgia threshold lowers as one ages, and it appears that by the 4th or 5th decade (30’s and 40’s) the aging threshold has reached a “predictable” level – where fibromyalgia can take hold. Hence the increased frequency of fibromyalgia complaints in this age range.

Once the pain threshold drops below the body’s ability to inhibit potential / random chronic pain signals, the threshold is “breached.” Now, chronic pain signals have a better chance of propagating the amplified pain cascade of changes and lead to Fibromyalgia. (To read more on this cascade of changes, see “Fibromyalgia – Ultimately a Disease of Amplified Pain.")

Probable FM Cause # 2: TRAUMA

(See “Fibromyalgia as a Complication of Injuries.”)


Many people get fibromyalgia associated with another disease, particularly rheumatic and connective tissue diseases. After genetics and trauma, I believe this type of disease is the most common cause of Fibromyalgia. Conditions in this category that can lead to reactive fibromyalgia include rheumatoid arthritis, lupus, polymyalgia rheumatica, and autoimmune disorders such as thyroiditis and Sjogren’s syndrome. Fibromyalgia does not turn into rheumatoid arthritis, lupus, or other inflammatory conditions, however.

Probable FM Cause # 4: INFECTION

(See “Infection as One Possible Cause of Fibromyalgia.”)


These are synonymous with emotional trauma. These are not your everyday stresses. Rather they represent more severe stresses which can cause fibromyalgia. The mechanism is probably very similar to a physical trauma, only instead of a tissue injury, there is a stress injury that may disrupt the hypothalamic-pituitary-adrenal hormone regulation (the stress hormones).

Probable FM Cause # 6: CHEMICAL EXPOSURE

I’ve seen a number of patients who have developed fibromyalgia after chemical exposure. Usually they have inhaled fumes from offending chemicals which include petroleum oils, paint thinners, cleaning solvents, dyes, or gasses/fumes from burning products. Most of the time these patients are treated at the hospital, but have lingering symptoms and ultimately develop fibromyalgia. The mechanism whereby these chemical exposures cause fibromyalgia appears to be an allergic and/or autoimmune response that escalates and sets off the fibromyalgia cascade. Many people with fibromyalgia are sensitive to chemicals, drugs, and environmental allergens like pollen, dust and molds. A condition known as chemical sensitivity syndrome occurs when one becomes chronically fatigued and ill from exposures to various substances.

* * * *

Future Research

We may not know the specific cause for a particular individual, but every single person with fibromyalgia has a cause, and ongoing funding and research of this complicated condition will result in further understanding. Future research will continue to shed light on these factors:

1. More specific identification of Fibromyalgia subgroups and better delineation of the overall Fibromyalgia Spectrum (See “The Fibromyalgia Spectrum – Part of the Big Picture in Understanding Fibromyalgia.")

2. Better understanding of the actual pathological mechanism, and learning what specifically triggers fibromyalgia from a microscopic or cellular level.

3. The ability to predict who will get fibromyalgia and what happens over time, and to understand the risks.

4. Additional genetic research to identify specific gene markers or specific neurobiological factors that contribute to fibromyalgia. Genetic research could also identify healing factors or specific gene therapy.



1. "Familial occurrence of primary fibromyalgia," Archives of Physical Medicine and Rehabilitation, Jan 1989.

2. "Mechanisms of Disease: Genetics of Fibromyalgia," Nature Clinical Practice, Rheumatology, 2006.

3. "Epidemiology of Fibromyalgia," Current Pain and Headache Reports, 2003; "Genetics of Chronic Pain States," Best Practice & Research, Clinical Rhematology, 2007.

4. "Genetic linkage analysis of multicase families with fibromyalgia syndrome,"  Journal of Rheumatology, 1999.

5. "Will Gene Variant Discovery Explain Fibromyalgia?"

Note: This article is excerpted with kind permission from Dr. Pellegrino’s book, Fibromyalgia, Up Close & Personal © Anadem Publishing, Inc. and Mark Pellegrino, MD, 2005. You may purchase a copy of this highly recommended book by contacting Dr. Pellegrino's office at the Ohio Pain & Rehab Specialists Center (Phone: 330-498-9865, Toll-Free: 800-529-7500).

1 Star2 Stars3 Stars4 Stars5 Stars (60 votes, average: 4.25 out of 5)

12 thoughts on “Genetics – Fibromyalgia Suspect #1”

  1. uxordepp says:

    I can tell you that since I’ve been on thyroid medication (T3 only), my “Fibromyalgia” symptoms, including brain fog, body pain, fatigue, insomnia and depression have improved tremendously.

    I suspect hypothyroidism actually the same as fibro…it’s just that the lab tests for thyroid are so bad that when they come back normal, they tell you you have fibro…or that it’s all just in your head.

  2. janhall_us says:

    My mother has been diagnosed with both Fibromyalgia and Parkinson’s. I have very early memories of her always being sick and family and doctors calling her a hypochondriac.

    I first became of my Fibromyalgia when my first husband whom I adored was caught cheating on me and left me with two children under 5 and no job or place to live. Very definitely a stressful event! My doctor at the time diagnosed me with “Epstein-Barr Syndrome” and I managed my illness with careful budgeting of my energy for the next 25 years until I went through early menopause at age 48. This life event kicked the Fibromyalgia up to the point that I was unable to continue working outside the home in 2009 and have one of the worst cases of Fibromyalgia my doctor has seen.

    Thank you for this article; it all makes a bit more sense now.

  3. kastringer says:

    I refuse flu shots now since I got fibro symptoms after one of the few that I did get.

    I had allergy tests and stopped eating foods I am allergic to.

    I’ve been taking iodine,for bromine poisoning using Dr. Brownstein’s protocol.

    And boron for fluoride poisoning.

    I feel much, much better. I will be starting on thyroid soon.

  4. KathyCFS1989 says:

    I got sick in 1989. I can remember my first doctor visit.
    I was so exhausted,swollen glands and a fever for months that wore me down. The doctor tested me and said I had mononucleosis AGAIN. I had it at 12. He wanted to give me Deseryl…I said what is that ? He told me its for depression . I told him I am not depressed , I am sick, FIX ME !! I dont have time for this .
    So I just kept working ,then the loss of balance came on,brain fog….meanwhile I tried to cover it up and keep pushing, and I noticed my customers getting sick with pneumonina/bronchitis and I was starting to feel like Typhoid Mary !
    When ever I had a really bad day ,everyone around me got sick.
    So by 1990, I started hearing about it in the news. So I went to a Doctor that specialized in CFS.

    My blood tests were:
    Epstein Bar Antibodies = 1:1280
    Epstein Bar Nuclear Antibodies = Postive
    Epstein Bar Early Antigen = Positive
    HHV-6 IgG = Positive (my Mother did get Roseola every year.She passed away at 51.)

    Anti-Thyroid Antibodies = High
    Anti-Thyroglobulin AB = High
    Anti-Microsomal Antibody = High
    Anti-Nuclear Antibody = High
    Anti-Candida Antibody IgG = High
    Anti-Candida Antibody IgA = High
    Lymphocytes :
    T Helper Cells = High
    T Suppressor = Low
    Helper/Suppressor Ratio = High

    He said I was positive for all the tests available to diagnose CFS.
    I have been on Thyroid since 1990.Its not the answer 🙁
    I had a neck surgery in 1995, and that is when the Fibro really kicked in .My symptoms were more Chronic Fatigue and Immune Dysfuntion than Fibro…until the surgery.
    I am 60 now, and any bit of exercise or stress (even good stress !) has a price to pay.Very heat intolerant also . I have not given up ,but you have to give in.

    I heard about XMRV, wow… just in time. 20 years. And they still are not sure.
    All I can say is that I do think its a virus of some kind. I heard there was an XMRV “like” synthetic virus engineered in the 80s…Was that it ? Who knows. I am too old to care anymore.

    Quote from site:Surprisingly it was neither identical to MuLV nor to the novel xenotropic MuLV related retrovirus (XMRV) but showed 99% identity to a synthetic retrovirus which was engineered in the 1980s.
    Sick and Tired of Being Sick and Tired,

    1. KathyCFS1989 says:

      By the way, my doctor told me NOT to ever give blood. And I never did. He said they dont know enough about it, and it may be passed through blood ,similar to aids .

    2. TrudyBird says:

      Yep, I agree. My mother complained from the time I can remember that she didn’t feel well. After I was diagnosed with FM, I realized my mother must have had it all these years as well. It all made sense and boy… did I feel guilty thinking that it was all in her head. Dad was mean alcoholic. Mom and us kids went through a very hard time with him, plus I’ve had all kinds of emotional and physical trauma, surgeries. Stress has always been an issue with me. Because of finances and a very sick husband I’m now broken out in a horrible case of hives that I’ve had for the last 5 months. You wonder…does it ever stop? My thyroid is fine. The hot flashes are horrible. Had a hyst at 27 and went on HRT. I’m going to be 60 in November and have been off of HRT for the last 2 years, but I’m trying to go cold turkey and tough it out. I take Prozac and antihisamines for the hives (it’s not working) and do my best to budget and save my energy. My BP is great and my blood glucose excellent. So much for the golden years! Ha! I still try to be active in local theater and get out, but it’s getting harder. I work full time, too. I have to. Any solutions that doesn’t cost much? At least my migraines are gone now that I’m off HRT. Had those buggers ever since I had gone on HRT but didn’t associate them (nor did my doctors)with the migraines. They went away as soon as I stopped taking hormone replacement therapy. Which is worse? Constant hot flashes or migraines. I’ll take the hot flashes I guess. 🙂

  5. mazinoz says:

    I agree that there is evidence of a genetic basis for fibromyalgia. I was told in my twenties I had Hypermobility Syndrome -Prof John Yorke [rheumatologist] but GP insisted Fibromyalgia and even refused to refer me to Prof Yorke for management of pain etc.

    Due to my experiences I would like to urge all patients with the FMS diagnosis to insist on tests to exclude caeliac disease and hypermobility syndrome, before accepting the FMS diagnosis.

    Articles by Dr Bravo [rheumatologist] and scientific articles on POTS and hypermobility have given strong evidence for a parasympathetic dysautonomia associated with hypermobility syndrome. This explains the non-articular symptoms such as migraine, low blood pressure, respiratory problems eg: hayfever, previously not explained by a strictly articular model for hypermobility syndrome. Basically the joint pain being seen as due to stress fractures brought on by over-extension of joints.

    On a personal level, myself and a niece have both found an improvement in stamina and energy levels on a low tyramine diet. Tyramine is also related to migraine. But I came across, which deals with a genetically based dysautonomia that responds well to low tyramine diet.

    The fibromyalgia diagnosis may be used by GP’s to placate patients with OTHER problems such as hypermobility syndrome or caeliac disease that they have not even considered, much less definitely excluded. Therefore I urge patients to consult specialists such as rheumatologists or gastroenterologists before accepting the FMS diagnosis. Of course, there is also a possibility they have a combination of these problems, and eventually genetic testing will provide a definitive diagnosis.

  6. Veronika says:

    I was diagnosed with fibromyagia in the 90’s before i had ever heard of it. By then I had lived with chronic pain my entire life. Now I KNOW THAT what fms really is Long term untreated or undertreated hypothyroidism. See It is so difficult to find this out. I read all the fms books and then all the thyroid books. The testing for thyroid the last forty years is why we are all left SUFFERING!!!!!. The TSH blood test is keeping us sick. the drug companies are making a fortune and we are not getting better. Not me. I know the reaL problem now. I went a lifetime of not getting what i needed. ( my dad just died from it but they said he everything else but it. They never treated him for it. you could see it all over his face and body. )

    My life now……I can sit, stand, walk, run, bike for loner than twenty minutes without being in horrible pain. I can run and win smaller 5k races at age 46 and 47. (Not this year at 48 though. ) I can still run 3 days a week about 7-8 miles a run. after being told i would never run again. i would never be cured of fibro. Please read Hypothyroidism: The Unsuspected Illness, LIving WEll with Hypothyroidism, and Hypothyroidism Type 2 and you will see why that your hypothyroidism has either not been found or that it has been undertreated and why it causing you so much pain. I too, had early menopause, i believe bc of the low thyroid. I also lost most of my hearing because i went untreated 40 years (well i lost most of it after 30 years). i had severve esophogitus in my late teens and early twenties. yes low thyroid causes all these problems and many more. migraines, etc, etc, Hope this helps. My life has changed!

  7. Roimata says:

    There is/was nobody in my family who was afflicted by Fibromyalgia.

    This illness began in 1966 after jabs of Tetanus Toxoid which made me very ill. Booster shot in 1975 and the adverse reaction was much worse.

    Now after any injury or reaction to medication relapses occur.

    Has anyone researched at the role of vaccines in the onset of Fibromyalgia?

  8. rector says:

    My supicion is that rather than being a “catch-all” diagnosis there will emerge a clearer clinical definition, and mor refined diagnostic tools in the future.
    In 1967, at the age of 25 I had low back pain: after 6 months of plaster I was seen by other specialists and diagnosed with ankylosing spondylitis.However in 1991 I was told that I did not have HLA B27, so culd not have AS, and therefor speciaialist treatment ceased.About 11 years later I was seen by a rheumatologist, (Under a specialist hospital for clergy), who checked my sore spots and read my history, and said fms. Following early retirement I have gradually collected a range of ‘supplementary’ conditions – gout, high blood pressure, night cramps/restless leg syndrome, type 2 diabetes, enlarged prostate,stomach problems, partia kidnet function. I suspect some of these may be linked to the high volume of NSAIDS that I took with the AS diagnosis..
    My eldest sister has thyroid problems, the next rheumatoid Arthritis, and my brother has a number of the same symptoms as I do, but at a level that means he has not gone for treatment, except that his kidney function means he will need regular dialisis any time now. In discussion with my siblings we agrre that my father may have had something similar to fms – he had a disability pension at the end of World War One for what wwould now probably be diagnosed as post traumatic stress syndrome: war expereinces + his mother died in a fire when he was 6.
    So in my family, of which i am the youngest, there appears to be a predisposition towards somthing similar to fms. What the precise trigger is that fires-up the disease interests me, as does the possibility that fms may weaken defences to other illnesses e.g fms = pain when moving= tendency to overweight=diabetes. I also think certain food tends to make it more active (for me tomatoes, citrus fruit, alcohol,recd meat).

  9. limbo says:

    Reading the out of balance, made me rememeber this, it was horrible. I just kept going, with four kids. I was precribed Valuim. This was 30-40 years ago.

    I used to exercise on a bicyle, the noticed my thighs were getting large. Hypertonicty.

    My father had fibro, but wasn’t diagnosed. We lived northern ND, and he went to Winipeg for ” mud bath” for pain. Interesting his sisters had drooping eyelids. there is a medical term for this.

    I have a daughter with discoid lupus, another daughter committed suicide at 49, 7 months ago.

    So don’t say it isn’t genetic. If the CDC didn’t use the funding for research correctly, many people wouldn’t have lived with pain, emotional as well.

  10. volcano1 says:

    Excellent article. It explains so much! I’ve had pain in my muscles since the age of 4. My mom has fibro as does my daughter and we suspect her daughter. HP Axis Syndrome runs in the family as does hypothyroidism. From the stories I’ve just read the one connection we all share is too much cortisol in our systems – whether it be from abusive home lives or stress from overwhelming living conditions. I think Dr. Pellegrino’s article is spot on and I’ll be interested in reading his book. BTW, I was dx’d in 1995 at OHSU by Dr. Robt Bennett. I also have Sjogrens Syndrome. I’m sure I’ve had FMS my entire life.

Leave a Reply