Genetic and epigenetic epidemiology of chronic widespread pain

Figures & data

Table 1 Summary of study characteristics of existing twin studies conducted on CWP, presented in the chronological order

Authors	Year	Variable	Cohort	n	h^2
Kato et al^Citation5	2006	CWP	Swedish Twin Registry	15,950 (53.5% female)	Female: 54% Male: 48%
Markkula et al^Citation43	2009	FM-like group	Finnish Twin Cohort	10,608 (54.2% female)	51%
Vehof et al^Citation46	2014	CWP	TwinsUK	4,465 (87.3% female)	27%
Malkin et al^Citation59	2014	CWP	TwinsUK	2,256 (100% female)	58%
Burri et al^Citation6	2015	CWP	TwinsUK	3,266 (100% female)	58%
Momi et al^Citation58	2015	CWP	TwinsUK	4,324 (89.7% female)	53%
Burri et al^Citation7	2015	CWP	TwinsUK	3,266 (100% female)	71%

Abbreviations: CWP, chronic widespread pain; FM, fibromyalgia.

Figure 1 Summary of the three multivariate twin studies exploring the genetic and environmental covariation between CWP and a range of functional somatic syndromes and psychological comorbidities.^6,12,46

Notes: In all the three studies, a common pathway model provided the best fit to the data, indicating the existence of latent phenotypes that underlie the covariation between CWP and the other included variables: F1 = latent phenotype identified in Vehof et al’s study,⁴⁶ F2_A = latent phenotype identified in Burri et al’s study;⁶ F3_A+B = latent phenotypes identified in Kato et al’s study.¹²
Abbreviations: CF, chronic fatigue; CWP, chronic widespread pain; DED, dry eye disease; GAD, generalized anxiety disorder; IBS, irritable bowel syndrome; PP, pelvic pain.

Table 2 Summary of existing molecular genetic studies on CWP presented in chronological order

Authors	Year	Sample and size	Ethnic origin	Main phenotype	Findings/implicated genes
Holliday et al^Citation50	2009	EPIFUND cohort; n=1,189	Caucasian (United Kingdom)	CWP	Haplotype frequencies for the “pain-protective” haplotype and allele frequencies for the OPRMI. SNPs did not differ between CWP individuals and controls
Hocking et al^Citation51	2010	Subjects from a British Cohort Study; n=7,083	Caucasian (United Kingdom)	Nonpain, nonchronic pain, chronic regional pain, CWP	1) Association of ADRB2 SNPs and CWP and pain status (nonchronic pain, chronic regional pain) 2) Association of ADRB2 haplotypes and pain status 2) No association of genetic COMT gene variants and reported chronic pain
Nicholl et al^Citation48	2011	EPIFUND (discovery) cohort; n=336 European Male Aging (validation) cohort; n=1,132	Caucasian (United Kingdom) Caucasian (Europe)	Number of pain sites, CWP	1) Association of SNPs in TPH2 and serotonin receptor (5-HTR2A) genes and CWP in the discovery cohort 2) Replication of HTR2A association in validation cohort
Skouen et al^Citation52	2012	Adolescents attending a 17-year cohort review; n=1,004	Caucasian (Western Australian)	Pain status	1) Risk factors for chronic pain and number of pain sites: female gender and mental health 2) Association of SNP in ADBR2 gene with chronic musculoskeletal pain
Peters et al^Citation53	2013	Several European cohorts; n=16,568	Caucasian (Europe)	CWP	Association of CCT5 and FATA173B genes with 30% higher risk for CWP

Abbreviations: CWP, chronic widespread pain; EPIFUND, Epidemiological study of functional disorders; SNP, single-nucleotide polymorphism.

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