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Rare SLC13A1 variants associate with intervertebral disc disorder highlighting role of sulfate in disc pathology.

Gyda BjornsdottirLilja StefansdottirGudmar ThorleifssonPatrick SulemKristjan NorlandEgil FerkingstadAsmundur OddssonFlorian ZinkSigrun H LundMuhammad Sulaman NawazG Bragi WaltersAstros Th SkuladottirSigurjon A GudjonssonGudmundur EinarssonGisli Hreinn HalldorssonValgerdur BjarnadottirGardar SveinbjornssonAnna HelgadottirUnnur StyrkársdóttirLarus J GudmundssonOle Birger Vesterager PedersenThomas Folkmann HansenThomas M WergeKarina BanasikAnders TroelsenSøren Thorgaard SkouLise Wegner ThørnerChristian ErikstrupKaspar Rene NielsenSusan Mikkelsennull nullnull nullIngileif JónsdóttirAron BjornssonIngvar H OlafssonElfar UlfarssonJosep BlondalArnor VikingssonSoren BrunakSisse Rye OstrowskiHenrik UllumUnnur ThorsteinsdottirHreinn StefánssonDaníel F GuðbjartssonThorgeir E ThorgeirssonKári Stefánsson
Published in: Nature communications (2022)
Back pain is a common and debilitating disorder with largely unknown underlying biology. Here we report a genome-wide association study of back pain using diagnoses assigned in clinical practice; dorsalgia (119,100 cases, 909,847 controls) and intervertebral disc disorder (IDD) (58,854 cases, 922,958 controls). We identify 41 variants at 33 loci. The most significant association (OR IDD  = 0.92, P = 1.6 × 10 -39 ; OR dorsalgia  = 0.92, P = 7.2 × 10 -15 ) is with a 3'UTR variant (rs1871452-T) in CHST3, encoding a sulfotransferase enzyme expressed in intervertebral discs. The largest effects on IDD are conferred by rare (MAF = 0.07 - 0.32%) loss-of-function (LoF) variants in SLC13A1, encoding a sodium-sulfate co-transporter (LoF burden OR = 1.44, P = 3.1 × 10 -11 ); variants that also associate with reduced serum sulfate. Genes implicated by this study are involved in cartilage and bone biology, as well as neurological and inflammatory processes.
Keyphrases
  • copy number
  • genome wide association study
  • genome wide
  • clinical practice
  • oxidative stress
  • bone mineral density
  • blood brain barrier
  • postmenopausal women
  • subarachnoid hemorrhage