Low Back and Common Widespread Pain Share Common Genetic Determinants

Low back (LBP) and chronic widespread musculoskeletal pain (CWP) both have a significant genetic component and are associated with increased body mass index (BMI). We examined whether LBP and CWP share common genetic factors, and to what extent this correlation is modified by the genetic factors influencing BMI. Genetic analysis of binary traits such as pain is not simple, particularly if their risk is associated with age or other quantitative traits. Implementing Falconer's polygenic threshold concept for dichotomous traits inheritance, we developed new software to examine the extent of the genetic influence on LBP and CWP under age and BMI dependence. The analysis was conducted on 3266 and 2256 UK female twins, assessed for LBP and CWP, respectively. Analysis of the liability scores with threshold to LBP and CWP established substantial contribution of genetic factors to their variation (h2 > 0.60, p<0.004‐0.0003) and covariation (p=3.1E‐08). Some 39% of the CWP and 70% of the LBP heritability estimates were attributable to genetic effects shared by both phenotypes, and 40% and 67% of the residual variation is caused by environmental factors simultaneously affecting both pain syndromes. However, contribution of BMI to variation/covariation of both pain phenotypes—although statistically highly significant (p∼10‐7)—was not determinative.

[1]  Jianxin Shi,et al.  Genetic relationship between five psychiatric disorders estimated from genome-wide SNPs , 2013, Nature Genetics.

[2]  A. Friedlander,et al.  Original Contribution Associations of Body Mass Index and Body Height with Low Back Pain in 829,791 Adolescents , 2022 .

[3]  How meaningful are heritability estimates of liability? , 2013, Human Genetics.

[4]  Ivar Heuch,et al.  Body Mass Index as a Risk Factor for Developing Chronic Low Back Pain: A Follow-up in the Nord-Trøndelag Health Study , 2013, Spine.

[5]  Bernadette A. Thomas,et al.  Disability-adjusted life years (DALYs) for 291 diseases and injuries in 21 regions, 1990–2010: a systematic analysis for the Global Burden of Disease Study 2010 , 2012, The Lancet.

[6]  Blair H. Smith,et al.  Genome-wide association study meta-analysis of chronic widespread pain: evidence for involvement of the 5p15.2 region , 2012, Annals of the rheumatic diseases.

[7]  Dorret I. Boomsma,et al.  Sex Differences in Genetic Architecture of Complex Phenotypes? , 2012, PloS one.

[8]  G. Knudsen,et al.  Twin studies of pain , 2012, Clinical genetics.

[9]  T. Spector,et al.  Lumbar disc degeneration and genetic factors are the main risk factors for low back pain in women: the UK Twin Spine Study , 2011, Annals of the rheumatic diseases.

[10]  C. Power,et al.  Diet, lifestyle and chronic widespread pain: results from the 1958 British Birth Cohort Study. , 2011, Pain research & management.

[11]  T. Spector,et al.  Pain reporting at different body sites is explained by a single underlying genetic factor , 2010, Rheumatology.

[12]  O. Vasseljen,et al.  Association between physical exercise, body mass index, and risk of fibromyalgia: Longitudinal data from the Norwegian Nord‐Trøndelag Health Study , 2010, Arthritis care & research.

[13]  Ivar Heuch,et al.  The Impact of Body Mass Index on the Prevalence of Low Back Pain: The HUNT Study , 2010, Spine.

[14]  H. Ackermann,et al.  Chronic pain in German general practice. , 2009, Pain medicine.

[15]  Werner Vach,et al.  Heritability of spinal pain and consequences of spinal pain: a comprehensive genetic epidemiologic analysis using a population-based sample of 15,328 twins ages 20-71 years. , 2009, Arthritis and rheumatism.

[16]  K. Kendler,et al.  Structure of genetic and environmental risk factors for dimensional representations of DSM–IV anxiety disorders , 2009, British Journal of Psychiatry.

[17]  R. Lipton,et al.  Chronic Pain and Obesity in Elderly People: Results from the Einstein Aging Study , 2009, Journal of the American Geriatrics Society.

[18]  A. Silman,et al.  Investigating the determinants of international differences in the prevalence of chronic widespread pain: evidence from the European Male Ageing Study , 2008, Annals of the rheumatic diseases.

[19]  B. Gerdle,et al.  Prevalence of widespread pain and associations with work status: a population study , 2008, BMC musculoskeletal disorders.

[20]  A. Bolotin,et al.  A cross-sectional study of the relationship between body mass index and clinical characteristics, tenderness measures, quality of life, and physical functioning in fibromyalgia patients , 2008, Clinical Rheumatology.

[21]  J. Kaprio,et al.  Heritability of low back pain and the role of disc degeneration , 2007, PAIN.

[22]  D. Rubin.  Epidemiology and risk factors for spine pain. , 2007, Neurologic clinics.

[23]  P. Sullivan,et al.  Importance of genetic influences on chronic widespread pain. , 2006, Arthritis and rheumatism.

[24]  L. Fratiglioni,et al.  Heritability of an Age-Dependent Categorical Phenotype: Cognitive Dysfunction , 2006, Twin Research and Human Genetics.

[25]  D Posthuma,et al.  Mx Scripts Library: Structural Equation Modeling Scripts for Twin and Family Data , 2022 .

[26]  Tim D Spector,et al.  Structural, psychological, and genetic influences on low back and neck pain: a study of adult female twins. , 2004, Arthritis and rheumatism.

[27]  A. Silman,et al.  Chronic widespread pain in the population: a seven year follow up study , 2002, Annals of the rheumatic diseases.

[28]  M. Speechley,et al.  The London Fibromyalgia Epidemiology Study: the prevalence of fibromyalgia syndrome in London, Ontario. , 1999, The Journal of rheumatology.

[29]  D. Coggon,et al.  Natural History of Low Back Pain: A Longitudinal Study in Nurses , 1998, Spine.

[30]  D. Falconer.  Introduction to quantitative genetics. 1. ed. , 1984 .

[31]  C. Rn.  The multifactorial model for the inheritance of liability to disease and its implications for relatives at risk. , 1972 .

[32]  R. Curnow.  The multifactorial model for the inheritance of liability to disease and its implications for relatives at risk. , 1972, Biometrics.

[33]  D. Falconer.  The inheritance of liability to certain diseases, estimated from the incidence among relatives , 1965 .

[34]  H. Grüneberg,et al.  Introduction to quantitative genetics , 1960 .