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

dc.creatorBjornsdottir G., Stefansdottir L., Thorleifsson G., Sulem P., Norland K., Ferkingstad E., Oddsson A., Zink F., Lund S.H., Nawaz M.S., Bragi Walters G., Skuladottir A.T., Gudjonsson S.A., Einarsson G., Halldorsson G.H., Bjarnadottir V., Sveinbjornsson G., Helgadottir A., Styrkarsdottir U., Gudmundsson L.J., Pedersen O.B., Hansen T.F., Werge T., Banasik K., Troelsen A., Skou S.T., Thørner L.W., Erikstrup C., Nielsen K.R., Mikkelsen S., Andersen S., Brunak S., Burgdorf K., Hjalgrim H., Jemec G., Jennum P., Johansson P.I., Nielsen K.R., Nyegaard M., Bruun M.T., Pedersen O.B., Dinh K.M., Sørensen E., Ostrowski S., Johansson P.I., Gudbjartsson D., Stefánsson H., Þorsteinsdóttir U., 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., Jonsson H., Ingvarsson T., 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., Jonsdottir I., Bjornsson A., Olafsson I.H., Ulfarsson E., Blondal J., Vikingsson A., Brunak S., Ostrowski S.R., Ullum H., Thorsteinsdottir U., Stefansson H., Gudbjartsson D.F., Thorgeirsson T.E., Stefansson K., DBDS Genetic Consortium, GO Consortiumen
dc.date.accessioned2023-01-31T07:38:32Z
dc.date.available2023-01-31T07:38:32Z
dc.date.issued2022
dc.identifier10.1038/s41467-022-28167-1
dc.identifier.issn20411723
dc.identifier.urihttp://hdl.handle.net/11615/71706
dc.description.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. © 2022, The Author(s).en
dc.language.isoenen
dc.sourceNature Communicationsen
dc.source.urihttps://www.scopus.com/inward/record.uri?eid=2-s2.0-85123973763&doi=10.1038%2fs41467-022-28167-1&partnerID=40&md5=1f9f1d9374273c5e47aa63bf043b456e
dc.subjectthrombinen
dc.subjecttransforming growth factor alphaen
dc.subjectcotransporteren
dc.subjectSLC13A1 protein, humanen
dc.subjectsodium sulfateen
dc.subjectsulfateen
dc.subjectdisabilityen
dc.subjectgeneen
dc.subjectgene expressionen
dc.subjectpathologyen
dc.subjectserumen
dc.subjectsulfateen
dc.subjectadulten
dc.subjectageden
dc.subjectArticleen
dc.subjectbackacheen
dc.subjectblood samplingen
dc.subjectbone densityen
dc.subjectcohort analysisen
dc.subjectcontrolled studyen
dc.subjectdegenerative diseaseen
dc.subjectgene expressionen
dc.subjectgenetic variabilityen
dc.subjectgenotypeen
dc.subjecthumanen
dc.subjecthuman experimenten
dc.subjecthuman tissueen
dc.subjectinflammatory bowel diseaseen
dc.subjectintervertebral disc disorderen
dc.subjectintervertebral disken
dc.subjectmiddle ageden
dc.subjectmRNA expression levelen
dc.subjectosteoarthritisen
dc.subjectphenotypeen
dc.subjectproteomicsen
dc.subjectrisk factoren
dc.subjectRNA sequencingen
dc.subjectsingle nucleotide polymorphismen
dc.subjecttranscriptomicsen
dc.subject3' untranslated regionen
dc.subjectboneen
dc.subjectgeneticsen
dc.subjectgenome-wide association studyen
dc.subjectintervertebral disken
dc.subjectintervertebral disk degenerationen
dc.subjectintervertebral disk herniaen
dc.subjectmetabolismen
dc.subject3' Untranslated Regionsen
dc.subjectBone and Bonesen
dc.subjectGenome-Wide Association Studyen
dc.subjectHumansen
dc.subjectIntervertebral Discen
dc.subjectIntervertebral Disc Degenerationen
dc.subjectIntervertebral Disc Displacementen
dc.subjectSodium Sulfate Cotransporteren
dc.subjectSulfatesen
dc.subjectSymportersen
dc.subjectNature Researchen
dc.titleRare SLC13A1 variants associate with intervertebral disc disorder highlighting role of sulfate in disc pathologyen
dc.typejournalArticleen


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