| Title: | Rare SLC13A1 variants associate with intervertebral disc disorder highlighting role of sulfate in disc pathology |
| Journal: | Nature Communications |
| Published: | 2 Feb 2022 |
| Pubmed: | https://pubmed.ncbi.nlm.nih.gov/35110524/ |
| DOI: | https://doi.org/10.1038/s41467-022-28167-1 |
| URL: | https://www.nature.com/articles/s41467-022-28167-1.pdf |
| Citations: | 30 (26 in last 2 years) as of 8 Aug 2024 |
Publication 12572
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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.</p>
10 Keywords
- 3' Untranslated Regions
- Bone and Bones
- Genome-Wide Association Study
- Humans
- Intervertebral Disc
- Intervertebral Disc Degeneration
- Intervertebral Disc Displacement
- Sodium Sulfate Cotransporter
- Sulfates
- Symporters
44 Authors
- Gyda Bjornsdottir
- Lilja Stefansdottir
- Gudmar Thorleifsson
- Patrick Sulem
- Kristjan Norland
- Egil Ferkingstad
- Asmundur Oddsson
- Florian Zink
- Sigrun H. Lund
- Muhammad S. Nawaz
- G. Bragi Walters
- Astros Th. Skuladottir
- Sigurjon A. Gudjonsson
- Gudmundur Einarsson
- Gisli H. Halldorsson
- Valgerdur Bjarnadottir
- Gardar Sveinbjornsson
- Anna Helgadottir
- Unnur Styrkarsdottir
- Larus J. Gudmundsson
- Ole B. Pedersen
- Thomas Folkmann Hansen
- Thomas Werge
- Karina Banasik
- Anders Troelsen
- Soren T. Skou
- Lise Wegner Thørner
- Christian Erikstrup
- Kaspar Rene Nielsen
- Susan Mikkelsen
- Ingileif Jonsdottir
- Aron Bjornsson
- Ingvar H. Olafsson
- Elfar Ulfarsson
- Josep Blondal
- Arnor Vikingsson
- Soren Brunak
- Sisse R. Ostrowski
- Henrik Ullum
- Unnur Thorsteinsdottir
- Hreinn Stefansson
- Daniel F. Gudbjartsson
- Thorgeir E. Thorgeirsson
- Kari Stefansson
1 Application
| Application ID | Title |
|---|---|
| 24898 | Genetics of lumbar disc disease and associated sciatica |
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