title: Sequence variants in the CLDN14 gene associate with kidney stones and bone mineral density.
abstract: Kidney stone disease is a common condition. To search for sequence variants conferring risk of kidney stones, we conducted a genome-wide association study in 3,773 cases and 42,510 controls from Iceland and The Netherlands. We discovered common, synonymous variants in the CLDN14 gene that associate with kidney stones (OR = 1.25 and P = 4.0 x 10(-12) for rs219780[C]). Approximately 62% of the general population is homozygous for rs219780[C] and is estimated to have 1.64 times greater risk of developing the disease compared to noncarriers. The CLDN14 gene is expressed in the kidney and regulates paracellular permeability at epithelial tight junctions. The same variants were also found to associate with reduced bone mineral density at the hip (P = 0.00039) and spine (P = 0.0077).
authors: DeCODE genetics, Sturlugata 8, 101 Reykjavik, Iceland. gudmar.thorleifsson@decode.is
authors: Gudmar
authors: G
authors: Thorleifsson
authors: Hilma
authors: H
authors: Holm
authors: Vidar
authors: V
authors: Edvardsson
authors: G Bragi
authors: GB
authors: Walters
authors: Unnur
authors: U
authors: Styrkarsdottir
authors: Daniel F
authors: DF
authors: Gudbjartsson
authors: Patrick
authors: P
authors: Sulem
authors: Bjarni V
authors: BV
authors: Halldorsson
authors: Femmie
authors: F
authors: de Vegt
authors: Frank C H
authors: FC
authors: d'Ancona
authors: Martin
authors: M
authors: den Heijer
authors: Leifur
authors: L
authors: Franzson
authors: Claus
authors: C
authors: Christiansen
authors: Peter
authors: P
authors: Alexandersen
authors: Thorunn
authors: T
authors: Rafnar
authors: Kristleifur
authors: K
authors: Kristjansson
authors: Gunnar
authors: G
authors: Sigurdsson
authors: Lambertus A
authors: LA
authors: Kiemeney
authors: Magnus
authors: M
authors: Bodvarsson
authors: Olafur S
authors: OS
authors: Indridason
authors: Runolfur
authors: R
authors: Palsson
authors: Augustine
authors: A
authors: Kong
authors: Unnur
authors: U
authors: Thorsteinsdottir
authors: Kari
authors: K
authors: Stefansson
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001483:Base Sequence; D015519:Bone Density / Q000235:genetics*; D002118:Calcium / Q000378:metabolism; D002891:Chromosomes, Human, Pair 21 / Q000235:genetics; D057167:Claudins; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D007669:Kidney Calculi / Q000235:genetics*; D008565:Membrane Proteins / Q000235:genetics*; D008875:Middle Aged; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics*
chemical_list: D057167:Claudins; D008565:Membrane Proteins; D002118:Calcium; C422064:claudin 14