Genome-wide association study identifies RNF123 locus as associated with chronic widespread musculoskeletal pain
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  • Published on:
    Response to ‘Genome-wide association study identifies RNF123 locus as associated with chronic widespread musculoskeletal pain’ by Lee and Song
    • Md Shafiqur Rahman, Researcher King's College London
    • Other Contributors:
      • Maxim B Freidin, Research Fellow
      • Frances MK Williams, Professor

    We thank Professors Lee and Song for their interest in our genome-wide association study (GWAS) of chronic widespread musculoskeletal pain (CWP)[1]. Their correspondence has raised several methodological concerns. First, CWP is a prominent feature of fibromyalgia. Clinically, it’s impossible to diagnose fibromyalgia without having CWP[2]. Therefore, the relevance of our findings to fibromyalgia cannot be ignored although we were careful not to conflate the two traits and did not claim genetic association with fibromyalgia. Second, the authors raise the relationship of the traits with age and sex; we adjusted for these covariates in the discovery GWAS and replication study. The important issue of body mass index (BMI) was much debated in our experimental design meetings. We elected not to adjust for BMI in the study for the following reasons:- (i) adjustment for heritable covariates (such as BMI) are not recommended in GWAS as this can lead to collider bias[3, 4] (ii) we wanted to explore the shared heritability of BMI and CWP using genetic correlation, (iii) adjustment for BMI would have affected genetic correlation and partial genetic correlation estimates reported in the paper and (vi) while so few variants have been described to date using GWAS for CWP, we were keen not to reduce the variance in the phenotype even if that led us to identify variants pleiotropic for BMI and CWP. Third, we have selected our controls for GWAS carefully by excluding important diagnostic con...

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    Conflict of Interest:
    None declared.
  • Published on:
    Correspondence on ‘Genome-wide association study identifies RNF123 locus as associated with chronic widespread musculoskeletal pain’ by Rahman et al
    • Young Ho Lee, Professor Korea University Hospital
    • Other Contributors:
      • Gwan Gyu Song, Professor


    Correspondence on ‘Genome-wide association study identifies RNF123 locus as associated with chronic widespread musculoskeletal pain’ by Rahman et al

    Young Ho Lee, Gwan Gyu Song

    Department of Rheumatology, Korea University College of Medicine, Seoul, Korea

    Corresponding author:
    Young Ho Lee, MD, PhD
    Department of Rheumatology
    Korea University Anam Hospital, Korea University College of Medicine
    73, Goryeodae-ro, Seongbuk-gu, Seoul, 02841, Korea
    Tel: 822-920-5645, Fax: 822-922-5974, E-mail:

    This research received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors.

    Conflict of interest statement
    The authors have no financial or non-financial conflict of interest to declare.

    We have read with great interest the genome-wide association study (GWAS) on candidate genes for chronic widespread pain (CWP) described by Rahman and colleagues.1 This GWAS meta-analysis has shown a new association of the RNF123 locus and suggested a link of the ATP2C1 locus with CWP; however, the association between COMT locus and CWP was not replicated. Although the results were quite helpful for understanding the genetic basis of CWP, several methodological issues need to be addressed.
    To begin with, both CWP and fibromyalgia appear to be a part of a pain continuum in the ge...

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    Conflict of Interest:
    None declared.