Study Suggests Genetics Play Strong Role in Young Fibromyalgia Patients

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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.