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

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

Title: Rare SLC13A1 variants associate with intervertebral disc disorder highlighting role of sulfate in disc pathology
Author: Nielsen, K.R.
Pedersen, O.B.
Sørensen, E.
Ostrowski, S.
Johansson, P.I.
Gudbjartsson, D.
Stefansson, H.
Larsen, M.A.H.
Didriksen, M.
Sækmose, S.
... 67 more authors Show all authors
Date: 2022-02-02
Language:
Scope: 634
University/Institute: Landbúnaðarháskóli Íslands
Landspítali
School: Heilbrigðisvísindasvið
Heilbrigðisvísindasvið
Department: Skrifstofa þjónustusviðs
Raunvísindadeild
Læknadeild
Kvenna- og barnaþjónusta
Iðnaðarverkfræði-, vélaverkfræði- og tölvunarfræðideild
Verkfræðideild
Lyfjafræðideild
Lyflækninga- og bráðaþjónusta
Matvæla- og næringarfræðideild
Jarðvísindadeild
Önnur svið
Rannsóknaþjónusta
Series: Nature Communications; 13(1)
ISSN: 2041-1723
DOI: https://doi.org/10.1038/s41467-022-28167-1
Subject: Heila- og taugaskurðlæknisfræði; Gigtarlæknisfræði; Náttúrufræðingar; Intervertebral Disc Degeneration; Intervertebral Disc Displacement; Back Pain; Genome-Wide Association Study; Bone and Bones/metabolism; Intervertebral Disc/metabolism; Humans; Symporters/genetics; Sodium Sulfate Cotransporter/genetics; Sulfates/metabolism; Intervertebral Disc Degeneration/genetics; Intervertebral Disc Displacement/genetics; 3' Untranslated Regions; Physics and Astronomy (all); Chemistry (all); Biochemistry, Genetics and Molecular Biology (all)
URI: https://hdl.handle.net/20.500.11815/3898

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Citation:

Nielsen , K R , Pedersen , O B , Sørensen , E , Ostrowski , S , Johansson , P I , Gudbjartsson , D , Stefansson , H , Larsen , M A H , Didriksen , M , Sækmose , S , Zeggini , E , Hatzikotoulas , K , Southam , L , Gilly , A , Barysenka , A , van Meurs , J B J , Boer , C G , Uitterlinden , A G , Styrkársdóttir , U , Stefánsdóttir , L , Esko , T , Mägi , R , Teder-Laving , M , Ikegawa , S , Terao , C , Takuwa , H , Meulenbelt , I , Coutinho de Almeida , R , Kloppenburg , M , Tuerlings , M , Slagboom , P E , Nelissen , R R G H H , Valdes , A M , Mangino , M , Tsezou , A , Zengini , E , Alexiadis , G , Babis , G C , Cheah , K S E , Wu , T T , Samartzis , D , Cheung , J P Y , Sham , P C , Kraft , P , Kang , J H , Hveem , K , Zwart , J-A , Luetge , A , Skogholt , A H , Johnsen , M B , Thomas , L F , Winsvold , B , Gabrielsen , M E , Lee , M T M , Zhang , Y , Lietman , S A , Shivakumar , M , Smith , G D , Tobias , J H , Hartley , A , Gaunt , T R , Zheng , J , Wilkinson , J M , Steinberg , J , Morris , A P , Ulfarsson , E , Blondal , J , Brunak , S , Ostrowski , S R , Ullum , H , Þorsteinsdóttir , U , Stefansson , H , Gudbjartsson , D F , Thorgeirsson , T E , Stefansson , K , DBDS Genetic Consortium & GO Consortium 2022 , ' Rare SLC13A1 variants associate with intervertebral disc disorder highlighting role of sulfate in disc pathology ' , Nature Communications , vol. 13 , no. 1 , 634 , pp. 634 . https://doi.org/10.1038/s41467-022-28167-1

Abstract:

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 (ORIDD = 0.92, P = 1.6 × 10−39; ORdorsalgia = 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.

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