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Rare SLC13A1 variants associate with intervertebral disc disorder highlighting role of sulfate in disc pathology
- Source :
- Nature Communications, 13(1):634. Nature Publishing Group, Nature Communications, Vol 13, Iss 1, Pp 1-13 (2022), Bjornsdottir, 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, 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 Consortium 2022, ' Rare SLC13A1 variants associate with intervertebral disc disorder highlighting role of sulfate in disc pathology ', Nature Communications, vol. 13, 634 . https://doi.org/10.1038/s41467-022-28167-1, Bjornsdottir, G, Stefánsdóttir, 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, Styrkársdóttir, 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 R, Johansson, P I, Gudbjartsson, D F, Stefansson, 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, Consortium, DBDS G & Consortium, GO 2022, ' Rare SLC13A1 variants associate with intervertebral disc disorder highlighting role of sulfate in disc pathology ', Nature Communications, vol. 13, no. 1, 634 . https://doi.org/10.1038/s41467-022-28167-1, Bjornsdottir, 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, DBDS Genetic Consortium, 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 & Nyegaard, M 2022, ' Rare SLC13A1 variants associate with intervertebral disc disorder highlighting role of sulfate in disc pathology ', Nature Communications, vol. 13, no. 1, 634 . https://doi.org/10.1038/s41467-022-28167-1, Bjornsdottir, G, Stefánsdóttir, 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, Styrkársdóttir, 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, DBDS Genetic Consortium, GO Consortium, 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 & Nyegaard, M 2022, ' Rare SLC13A1 variants associate with intervertebral disc disorder highlighting role of sulfate in disc pathology ', Nature Communications, vol. 13, 634 . https://doi.org/10.1038/s41467-022-28167-1
- Publication Year :
- 2022
-
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.
- Subjects :
- Science
General Physics and Astronomy
Intervertebral Disc Degeneration
Intervertebral Disc/metabolism
Bone and Bones/metabolism
Bone and Bones
General Biochemistry, Genetics and Molecular Biology
health services administration
Humans
Sodium Sulfate Cotransporter/genetics
Intervertebral Disc
3' Untranslated Regions
health care economics and organizations
Sodium Sulfate Cotransporter
Symporters/genetics
Multidisciplinary
Symporters
Sulfates
General Chemistry
equipment and supplies
Intervertebral Disc Degeneration/genetics
Intervertebral Disc Displacement/genetics
Sulfates/metabolism
population characteristics
human activities
Intervertebral Disc Displacement
Genome-Wide Association Study
Subjects
Details
- Language :
- English
- ISSN :
- 20411723
- Database :
- OpenAIRE
- Journal :
- Nature Communications, 13(1):634. Nature Publishing Group, Nature Communications, Vol 13, Iss 1, Pp 1-13 (2022), Bjornsdottir, 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, 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 Consortium 2022, ' Rare SLC13A1 variants associate with intervertebral disc disorder highlighting role of sulfate in disc pathology ', Nature Communications, vol. 13, 634 . https://doi.org/10.1038/s41467-022-28167-1, Bjornsdottir, G, Stefánsdóttir, 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, Styrkársdóttir, 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 R, Johansson, P I, Gudbjartsson, D F, Stefansson, 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, Consortium, DBDS G & Consortium, GO 2022, ' Rare SLC13A1 variants associate with intervertebral disc disorder highlighting role of sulfate in disc pathology ', Nature Communications, vol. 13, no. 1, 634 . https://doi.org/10.1038/s41467-022-28167-1, Bjornsdottir, 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, DBDS Genetic Consortium, 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 & Nyegaard, M 2022, ' Rare SLC13A1 variants associate with intervertebral disc disorder highlighting role of sulfate in disc pathology ', Nature Communications, vol. 13, no. 1, 634 . https://doi.org/10.1038/s41467-022-28167-1, Bjornsdottir, G, Stefánsdóttir, 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, Styrkársdóttir, 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, DBDS Genetic Consortium, GO Consortium, 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 & Nyegaard, M 2022, ' Rare SLC13A1 variants associate with intervertebral disc disorder highlighting role of sulfate in disc pathology ', Nature Communications, vol. 13, 634 . https://doi.org/10.1038/s41467-022-28167-1
- Accession number :
- edsair.doi.dedup.....a437f3a611a9b487e04c29f022013bff
- Full Text :
- https://doi.org/10.1038/s41467-022-28167-1