Is Low Back Pain a Genetic Problem?

Abstract

Twin studies indicate that the (1) heritability of low back pain (LBP) is considerable varying between 30 and 46% depending on the setting, and (2) disc degeneration (DD) has a strong mediating effect in LBP with 11 to 13% of shared genetic effects. Until now, genetic research in LBP has focused on candidate genes; disease-related single-nucleotide polymorphisms have been found in structural, immune system, and nociception-related proteins. So far, no genome-wide association studies (GWAS) have been published in LBP. GWAS data will undoubtedly increase our knowledge on genetics of LBP. However, GWAS is able to detect only common variants (> 5% MAF) and it is reasonable to expect that rare variants, obtained by whole-genome sequencing, have a role in LBP as well as in other complex disorders. Environmental factors have a significant role in LBP. Epigenetics describes heritable information not encoded in DNA. Different epigenetic mechanisms include such as methylation of cytosines in DNA, posttranslational modifications (mainly acetylation) of histones and microRNAs. Epigenetic regulation has an important role in complex disorders and preliminary evidence indicates that epigenetic mechanisms are important in DD as well. The future of LBP genetics requires first an unambiguous phenotype (mere subjective experience of pain is not enough). Discovery of objective endophenotypes of LBP may clarify the phenotype issue. Second, we need to establish large consortiums with genetic and epigenetic sample collection and systematic assessment of environmental (includes also psychological factors) determinants. Methodologically, bioinformatics will be most likely the rate-limiting step—at least in the beginning. Genetic analyses will most likely shift from common-to-rare variants—covering more extensively also the nonprotein coding area. However, in time, genetic research in LBP will evolve and become more commonplace. Disclosure of Interest None declared References Battié MC, Videman T, Levalahti E, Gill K, Kaprio J. Heritability of low back pain and the role of disc degeneration. Pain 2007;131(3):272–280 Denk F, McMahon SB, Tracey I. Pain vulnerability: a neurobiological perspective. Nat Neurosci 2014;17(2):192–200 Diatchenko L, Fillingim RB, Smith SB, Maixner W. The phenotypic and genetic signatures of common musculoskeletal pain conditions. Nat Rev Rheumatol 2013;9(6):340–350 J Eskola P, Männikkö M, Samartzis D, Karppinen J. Genome-wide association studies of lumbar disc degeneration-are we there yet? Spine J 2014;14(3):479–482 Foulkes T, Wood JN. Pain genes. PLoS Genet 2008;4(7):e1IN1.02086 Livshits G, Popham M, Malkin I, et al. Lumbar disc degeneration and genetic factors are the main risk factors for low back pain in women: the UK Twin Spine Study. Ann Rheum Dis 2011;70(10):1740–1745 Mogil JS. Pain genetics: past, present and future. Trends Genet 2012;28(6):258–266 Näkki A, Battié MC, Kaprio J. Genetics of disc-related disorders: current findings and lessons from other complex diseases. Eur Spine J 2013; July 10 (Epub ahead of print)