Heritability of the Fibromyalgia Phenotype Varies by Age

Abstract

Objective. Many studies suggest a strong familial component to fibromyalgia (FM). However, those studies have nearly all been confined to individuals with primary FM, i.e., FM without any other accompanying disorder. The current 2011 and 2016 criteria for diagnosing FM construct a score using a combination of the number of painful body sites and the severity of somatic symptoms (FM score). This study was undertaken to estimate the genetic heritability of the FM score across sex and age groups to identify subgroups of individuals with greater heritability, which may help in the design of future genetic studies.Methods. We collected data on 26,749 individuals of European ancestry undergoing elective surgery at the University of Michigan (Michigan Genomics Initiative study). We estimated the single-nucleotide polymorphism-based heritability of FM score by age and sex categories using genome-wide association study data and a linear mixed-effects model.Results. Overall, the FM score had an estimated heritability of 13.9% (SE 2.9%) (P = 1.6 × 10 −7 ). Estimated FM score heritability was highest in individuals ≤50 years of age (23.5%; SE 7.9%) (P = 3.0 ×10 −4 ) and lowest in individuals >60 years of age (7.5%; SE 8.1%) (P = 0.41). These patterns remained the same when we analyzed FM as a case-control phenotype. Even though women had an ~30% higher average FM score than men across age categories, FM score heritability did not differ significantly by sex.Conclusion. Younger individuals appear to have a much stronger genetic component to the FM score than older individuals. Older individuals may be more likely to have what was previously called "secondary FM." Regardless of the cause, these results have implications for future genetic studies of FM and associated conditions.

One year in review 2021: fibromyalgia

“…Several studies have suggested that FM has a familial component. Using genome-wide association studies (GWAS) data, Dutta et al (28) investigated the genetic heritability of a continuous measure of FM severity, the FM score, calculated by summing the WPI and SSS. The study demonstrated that younger individuals (≤50 years) appear to have a much stronger genetic component to the FM score than older individuals, who were more likely to have autoimmune or structural causes of pain.…”

Key Milestones Contributing to the Understanding of the Mechanisms Underlying Fibromyalgia

“…Genetic factors modulate activity in relevant neurobiological systems, such as stress-response systems [ 75 , 76 , 77 ]. Further understanding of the relationship of genetic factors to fibromyalgia phenotypes, such as early onset fibromyalgia, may allow for different management strategies in different subsets [ 78 ].…”

A distinctive profile of family genetic risk scores in a Swedish national sample of cases of fibromyalgia, irritable bowel syndrome, and chronic fatigue syndrome compared to rheumatoid arthritis and major depression

“…Several studies suggest a familial/genetic predisposition for FSD. Moderate levels of heritability were found in twin studies of FM (Dutta et al, 2020), IBS (Svedberg, Johansson, Wallander, & Pedersen, 2008), and CFS (Buchwald et al, 2001). Which particular genes are responsible remains unknown as genome-wide association studies of FSD are in early stages, with limited power and/or shallow phenotyping (Bonfiglio et al, 2018;Docampo et al, 2014;Schlauch et al, 2016).…”