Rare SLC13A1 variants associate with intervertebral disc disorder highlighting role of sulfate in disc pathology-Reference-Cited by-同舟云学术

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

Published:2022-02-02 Issue:1 Volume:13 Page:
ISSN:2041-1723
Container-title:Nature Communications
language:en
Short-container-title:Nat Commun

Author:

Bjornsdottir Gyda^ORCID,Stefansdottir Lilja,Thorleifsson Gudmar,Sulem Patrick^ORCID,Norland Kristjan,Ferkingstad Egil^ORCID,Oddsson Asmundur,Zink Florian,Lund Sigrun H.,Nawaz Muhammad S.^ORCID,Bragi Walters G.^ORCID,Skuladottir Astros Th.^ORCID,Gudjonsson Sigurjon A.,Einarsson Gudmundur^ORCID,Halldorsson Gisli H.^ORCID,Bjarnadottir Valgerdur,Sveinbjornsson Gardar,Helgadottir Anna^ORCID,Styrkarsdottir Unnur^ORCID,Gudmundsson Larus J.,Pedersen Ole B.^ORCID,Hansen Thomas Folkmann^ORCID,Werge Thomas^ORCID,Banasik Karina^ORCID,Troelsen Anders^ORCID,Skou Soren T.^ORCID,Thørner Lise Wegner,Erikstrup Christian^ORCID,Nielsen Kaspar Rene,Mikkelsen Susan,Andersen Steffen,Brunak Søren^ORCID,Burgdorf Kristoffer,Hjalgrim Henrik,Jemec Gregor,Jennum Poul,Johansson Per Ingemar,Nielsen Kasper Rene,Nyegaard Mette,Bruun Mie Topholm,Pedersen Ole Birger,Dinh Khoa Manh,Sørensen Erik,Ostrowski Sisse,Johansson Pär Ingemar,Gudbjartsson Daniel,Stefánsson Hreinn,Þorsteinsdóttir Unnur,Larsen Margit Anita Hørup,Didriksen Maria,Sækmose Susanne,Zeggini Eleftheria,Hatzikotoulas Konstantinos,Southam Lorraine,Gilly Arthur,Barysenka Andrei,van Meurs Joyce B. J.,Boer Cindy G.,Uitterlinden André G.,Styrkársdóttir Unnur,Stefánsdóttir Lilja,Jonsson Helgi,Ingvarsson Thorvaldur,Esko Tõnu,Mägi Reedik,Teder-Laving Maris,Ikegawa Shiro,Terao Chikashi,Takuwa Hiroshi,Meulenbelt Ingrid,Coutinho de Almeida Rodrigo,Kloppenburg Margreet,Tuerlings Margo,Slagboom P. Eline,Nelissen Rob R. G. H. H.,Valdes Ana M.,Mangino Massimo,Tsezou Aspasia,Zengini Eleni,Alexiadis George,Babis George C.,Cheah Kathryn S. E.,Wu Tian T.,Samartzis Dino,Cheung Jason Pui Yin,Sham Pak Chung,Kraft Peter,Kang Jae Hee,Hveem Kristian,Zwart John-Anker,Luetge Almut,Skogholt Anne Heidi,Johnsen Marianne B.,Thomas Laurent F.,Winsvold Bendik,Gabrielsen Maiken E.,Lee Ming Ta Michael,Zhang Yanfei,Lietman Steven A.,Shivakumar Manu,Smith George Davey,Tobias Jonathan H.,Hartley April,Gaunt Tom R.,Zheng Jie,Wilkinson J. Mark,Steinberg Julia,Morris Andrew P.,Jonsdottir Ingileif^ORCID,Bjornsson Aron,Olafsson Ingvar H.,Ulfarsson Elfar,Blondal Josep,Vikingsson Arnor,Brunak Soren,Ostrowski Sisse R.^ORCID,Ullum Henrik,Thorsteinsdottir Unnur,Stefansson Hreinn^ORCID,Gudbjartsson Daniel F.^ORCID,Thorgeirsson Thorgeir E.,Stefansson Kari^ORCID, ,

Abstract

AbstractBack 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.

Funder

Novo Nordisk

Novo Nordisk Fonden

European Commission

Publisher

Springer Science and Business Media LLC

Subject

General Physics and Astronomy,General Biochemistry, Genetics and Molecular Biology,General Chemistry,Multidisciplinary

Link

https://www.nature.com/articles/s41467-022-28167-1.pdf

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