Title: | Rare SLC13A1 variants associate with intervertebral disc disorder highlighting role of sulfate in disc pathology |
Author: |
... 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 |
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
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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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Description:Publisher Copyright: © 2022, The Author(s).
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