Identification of IL12RB1 as a novel systemic sclerosis susceptibility locus

Elena Lopez-Isac, Lara Bossini-Castillo, Sandra G. Guerra, Christopher Denton, Carmen Fonseca, Shervin Assassi, Xiaodong Zhou, Maureen D. Mayes, Carmen Pilar Simeon, Norberto Ortego-Centeno, Ivan Castellvi, Patricia Carreira, Olga Gorlova, Lorenzo Beretta, Alessandro Santaniello, Claudio Lunardi, Roger Hesselstrand, Annika Nordin, Gabriela Riemekasten, Torsten WitteNicolas Hunzelmann, Alexander Kreuter, Joerg H. W. Distler, Alexandre E. Voskuyl, Jeska de Vries-Bouwstra, Bobby P. Koeleman, Ariane Herrick, Jane Worthington, Timothy R. D. J. Radstake, Javier Martin

Research output: Contribution to journalDebate/Note/Editorial


ObjectiveLumbar spinal stenosis is one of the most commonly diagnosed spinal disorders in older adults. Although the pathophysiology of the clinical syndrome is not well understood, a narrow central canal or intervertebral foramen is an essential or defining feature. The aim of the present study was to estimate the magnitude of genetic versus environmental influences on central lumbar spinal stenosis and to investigate disc degeneration and stature or bone development as possible genetic pathways. MethodsA classic twin study with multivariate analyses considering lumbar level and other covariates was conducted. The study sample comprised 598 male twins (147 monozygotic and 152 dizygotic pairs), 35-70 years of age, from the population-based Finnish Twin Cohort. The primary phenotypes were central lumbar stenosis as assessed qualitatively on magnetic resonance imaging (MRI) and quantitatively measured dural sac cross-sectional area. Additional phenotypes (to examine possible genetic pathways) included disc bulging and standing height, as an indicator of overall skeletal size or development. ResultsThe heritability estimate (h(2)) for qualitatively assessed central lumbar spinal stenosis on MRI was 66.9% (95% confidence interval [95% CI] 56.8, 74.5). The broad-sense heritability estimate for dural sac cross-sectional area was 81.2% (95% CI 74.5, 86.1), with a similar magnitude of genetic influences across lumbar levels (h(2) = 72.4-75.6). The additive genetic correlation of quantitatively assessed stenosis and disc bulging was extremely high. There was no indication of shared genetic influences between stenosis and stature. ConclusionCentral lumbar spinal stenosis and associated dural sac dimensions are highly genetic, and disc degeneration (bulging) appears to be one pathway through which genes influence spinal stenosis.
Original languageEnglish
Pages (from-to)3521-3523
JournalArthritis & Rheumatology
Issue number12
Publication statusPublished - 2014

Subject classification (UKÄ)

  • Rheumatology and Autoimmunity


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