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Younger individuals (<50 years) have a stronger genetic component in their fibromyalgia score than older individuals (>60 years), according to a study published in Arthritis & Rheumatology.1
Studies that suggest a strong familial component to fibromyalgia have often focused on individuals with primary fibromyalgia who did not have another accompanying disorder, the study authors report. For this reason, they decided to focus on genetic heritability to calculate a fibromyalgia score—using the number of painful body sites and severity of somatic symptoms—across sex and age groups.
The authors’ goal was to find subgroups with greater heritability and to assess if heritability differs by sex or age at assessment.
Although there have been candidate gene and genome-wide association studies (GWAS) that compare allele frequencies (i.e., the incidence of a gene variant in a population) in fibromyalgia cases and controls, the results have been inconsistent, the authors write.
Study Population
The study included 26,749 people of European ancestry having elective surgery at the University of Michigan, Ann Arbor, who were part of the Michigan Genomics Initiative. The authors estimated the single-nucleotide polymorphism (SNP) based heritability of the fibromyalgia score by age and sex categories using data from GWAS and a linear mixed model (i.e., an extension of simple linear models to allow both fixed and random effects).
Fibromyalgia scores were dichotomized according to two different definitions: any individual with a fibromyalgia score of 13 or higher was considered an FM-Criteria 2011 case, and anyone with four of the five main body regions having pain and a Widespread Pain Index (WPI) score of 7 or higher and a Symptom Severity Index (SSI) score of 5 or higher was considered an FM-2016-modified case. Patients with a WPI score of 4–6 and an SSI score of 9 or higher were also considered an FM-2016-modified case.2,3
The genetic correlation of the score was estimated with psychiatric, personality, and autoimmune traits using GWAS summary statistics.
Patients were phenotyped preoperatively with a self-reported questionnaire of widespread pain and psychological status using ACR survey criteria for fibromyalgia.
Results
The mean patient age was 54.2 years, and 53.2% of patients were women. Nearly 11% had a fibromyalgia score of 0.
The fibromyalgia score had an estimated heritability of 13.9%. Younger people—those age 50 or under—had a higher estimated fibromyalgia score heritability (23.5%). At each age cut-off used by the authors, younger individuals had consistently higher heritability of their fibromyalgia score than older individuals.
Using the two different definitions of fibromyalgia, heritability was 8.6% for those classified as FM-2011 and 7.9% for those classified as FM-2016-modified.
The age categories of 40–50 and 50–60 had significantly higher fibromyalgia scores than those in the under-40 age category and those in the 60–70, 70–80 and 80–90 age categories.
The lowest heritability found was in those older than 60 (7.3%). The findings were the same when fibromyalgia was analyzed as a case-control phenotype.
Fibromyalgia score heritability did not differ significantly when comparing men and women, although women had about a 30% higher average fibromyalgia score than men across age categories. “Although the average fibromyalgia scores in women are higher than in men, the genetic contributions to fibromyalgia score variability do not differ significantly by sex in this sample size,” the authors write.
When analyzing pain measurement at different body sites, those age 50 or younger had a lower WPI score than those older than 50 (1.8 vs. 2.0, respectively). However, younger people in the study had a higher SSI score than older individuals (3.8 vs. 3.4, respectively). Women had higher WPI (2.1 vs. 1.6) and SSI (4.1 vs. 3.0) scores than men.
Age and sex were significantly associated with fibromyalgia, WPI and SSI. When analyzing the variance of sex or the effect of sex on fibromyalgia score by age category, no significant evidence to show showed an effect.
The authors also found a significant genetic correlation between fibromyalgia scores and psychiatric disorders, such
as attention-deficit/hyperactivity
disorder, neuroticism, major depressive symptoms and depressive symptoms. They also found a significant genetic correlation of the score with immune and autoimmune diseases, such as asthma and rheumatoid arthritis.
The study is the largest to the authors’ knowledge that analyzes genetic contributions to fibromyalgia scores.
Implications
“The variability in fibromyalgia score for younger individuals, which is potentially more likely to be primary fibromyalgia, appears to be more driven by genetic factors shared across individuals than in older individuals,” the authors write. “Older individuals may have a greater contribution of environmental factors to pain, a greater diversity of conditions that increase pain, and/or more susceptibility towards nociceptive pain. … Overall, our results suggest that genetic studies of fibromyalgia might have differing results depending on the age of the participants.”
In the future, the inclusion of younger patients in GWAS or large candidate gene studies may be beneficial, the authors write. In the past, these studies have focused on patients older than 50 or have not reported age at all.
“If comprised of the same number of individuals, studies focusing on younger individuals with pain may have more power to detect disease-genetic variant associations than studies of older individuals,” says study author Laura J. Scott, MPH, PhD, research professor, Department of Biostatistics, University of Michigan School of Public Health, Ann Arbor. Large-scale population studies that include a wide range of ages may offer the most power, such as a GWAS from 2019 that identified 39 loci for multi-site chronic pain, she says.4
One study limitation is that the sample in the current study is not population based, the authors write. Those who were included were scheduled for surgery and were more likely to have pain.
Although the authors do not have other research planned in this area, it would be interesting to identify genetic determinants of pain that overlap with psychiatric disorders and those that appear to be independent of them, Dr. Scott says.
Vanessa Caceres is a medical writer in Bradenton, Fla.
References
- Dutta D, Brummett CM, Moser SE, et al. Heritability of the fibromyalgia phenotype varies by age. Arthritis Rheumatol. 2020 May;72(5):815–823.
- Wolfe F, Clauw DJ, Fitzcharles MA, et al. The American College of Rheumatology preliminary diagnostic criteria for fibromyalgia and measurement of symptom severity. Arthritis Care Res. 2010 May;62(5):600–610.
- Wolfe F, Clauw DJ, Fitzcharles MA, et al. Fibromyalgia criteria and severity scales for clinical and epidemiological studies: A modification of the ACR preliminary diagnostic criteria for fibromyalgia. J Rheumatol. 2011 Jun ;38(6):1113–1122.
- Johnson KJA, Adams MJ, Nicholl BI, et al. Genome-wide association study of multisite chronic pain in UK Biobank. PLoS Genet. 2019 Jun 13;15(6):e1008164.
