Nonsense mutation in the LGR4 gene is associated with several human diseases and other traits.
Cast your vote
You can rate an item by clicking the amount of stars they wish to award to this item.
When enough users have cast their vote on this item, the average rating will also be shown.
Your vote was cast
Thank you for your feedback
Thank you for your feedback
Gudbjartsson, Daniel F
Magnusson, Olafur T
Walters, G Bragi
Frigge, Michael L
Helgadottir, Hafdis T
Ogmundsdottir, Margret H
Center, Jacqueline R
Nguyen, Tuan V
Eisman, John A
Jonasson, Jon G
Eyjolfsson, Gudmundur I
MetadataShow full item record
CitationNature 2013, 497(7450):517-20
AbstractLow bone mineral density (BMD) is used as a parameter of osteoporosis. Genome-wide association studies of BMD have hitherto focused on BMD as a quantitative trait, yielding common variants of small effects that contribute to the population diversity in BMD. Here we use BMD as a dichotomous trait, searching for variants that may have a direct effect on the risk of pathologically low BMD rather than on the regulation of BMD in the healthy population. Through whole-genome sequencing of Icelandic individuals, we found a rare nonsense mutation within the leucine-rich-repeat-containing G-protein-coupled receptor 4 (LGR4) gene (c.376C>T) that is strongly associated with low BMD, and with osteoporotic fractures. This mutation leads to termination of LGR4 at position 126 and fully disrupts its function. The c.376C>T mutation is also associated with electrolyte imbalance, late onset of menarche and reduced testosterone levels, as well as an increased risk of squamous cell carcinoma of the skin and biliary tract cancer. Interestingly, the phenotype of carriers of the c.376C>T mutation overlaps that of Lgr4 mutant mice.
DescriptionTo access publisher's full text version of this article. Please click on the hyperlink in Additional Links field.
RightsArchived with thanks to Nature
- Are bone mineral density loci associated with hip osteoporotic fractures? A validation study on previously reported genome-wide association loci in a Chinese population.
- Authors: Guo Y, Wang JT, Liu H, Li M, Yang TL, Zhang XW, Liu YZ, Tian Q, Deng HW
- Issue date: 2012 Jan 31
- Eye-open at birth phenotype with reduced keratinocyte motility in LGR4 null mice.
- Authors: Kato S, Mohri Y, Matsuo T, Ogawa E, Umezawa A, Okuyama R, Nishimori K
- Issue date: 2007 Oct 2
- Two Rare Mutations in the COL1A2 Gene Associate With Low Bone Mineral Density and Fractures in Iceland.
- Authors: Styrkarsdottir U, Thorleifsson G, Eiriksdottir B, Gudjonsson SA, Ingvarsson T, Center JR, Nguyen TV, Eisman JA, Christiansen C, Thorsteinsdottir U, Sigurdsson G, Stefansson K
- Issue date: 2016 Jan
- Pathway-based genome-wide association analysis identified the importance of regulation-of-autophagy pathway for ultradistal radius BMD.
- Authors: Zhang L, Guo YF, Liu YZ, Liu YJ, Xiong DH, Liu XG, Wang L, Yang TL, Lei SF, Guo Y, Yan H, Pei YF, Zhang F, Papasian CJ, Recker RR, Deng HW
- Issue date: 2010 Jul
- Association of P2X7 receptor polymorphisms with bone mineral density and osteoporosis risk in a cohort of Dutch fracture patients.
- Authors: Wesselius A, Bours MJ, Henriksen Z, Syberg S, Petersen S, Schwarz P, Jørgensen NR, van Helden S, Dagnelie PC
- Issue date: 2013 Apr