Common and rare variants associated with kidney stones and biochemical traits

被引：134

作者：

Oddsson, Asmundur ^{[1
]}

Sulem, Patrick ^{[1
]}

Helgason, Hannes ^{[1
,2
]}

Edvardsson, Vidar O. ^{[3
,4
,5
]}

Thorleifsson, Gudmar ^{[1
]}

Sveinbjoernsson, Gardar ^{[1
]}

Haraldsdottir, Eik ^{[1
]}

Eyjolfsson, Gudmundur I. ^{[6
]}

Sigurdardottir, Olof ^{[7
]}

Olafsson, Isleifur ^{[8
]}

Masson, Gisli ^{[1
]}

Holm, Hilma ^{[1
]}

Gudbjartsson, Daniel F. ^{[1
,2
]}

Thorsteinsdottir, Unnur ^{[1
,4
]}

Indridason, Olafur S. ^{[9
]}

Palsson, Runolfur ^{[4
,5
,9
]}

Stefansson, Kari ^{[1
,4
]}

机构：

[1] DeCODE Genet Amgen Inc, IS-101 Reykjavik, Iceland

[2] Univ Iceland, Sch Engn & Nat Sci, IS-101 Reykjavik, Iceland

[3] Landspitali, Childrens Med Ctr, IS-101 Reykjavik, Iceland

[4] Univ Iceland, Fac Med, IS-101 Reykjavik, Iceland

[5] Mayo Clin, Rare Kidney Stone Consortium, Rochester, MN USA

[6] Iceland Med Ctr Laeknasetrid, Lab Mjodd RAM, IS-109 Reykjavik, Iceland

[7] Akureyri Hosp, Dept Clin Biochem, IS-600 Akureyri, Iceland

[8] Landspitali Univ Hosp, Dept Clin Biochem, IS-101 Reykjavik, Iceland

[9] Landspitali, Div Nephrol, Internal Med Serv, Reykjavik, Iceland

来源：

NATURE COMMUNICATIONS | 2015年 / 6卷

关键词：

CALCIUM-SENSING RECEPTOR; SEQUENCE VARIANTS; GENE; DISEASE; NEPHROLITHIASIS; TRPV5; HYPOPHOSPHATASIA; HYPERCALCIURIA; MINERALIZATION; INSIGHTS;

D O I：

10.1038/ncomms8975

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

Kidney stone disease is a complex disorder with a strong genetic component. We conducted a genome-wide association study of 28.3 million sequence variants detected through whole-genome sequencing of 2,636 Icelanders that were imputed into 5,419 kidney stone cases, including 2,172 cases with a history of recurrent kidney stones, and 279,870 controls. We identify sequence variants associating with kidney stones at ALPL (rs1256328[T], odds ratio (OR) = 1.21, P = 5.8 x 10(-10)) and a suggestive association at CASR (rs7627468[A], OR = 1.16, P = 2.0 x 10(-8)). Focusing our analysis on coding sequence variants in 63 genes with preferential kidney expression we identify two rare missense variants SLC34A1 p.Tyr489Cys (OR = 2.38, P = 2.8 x 10(-5)) and TRPV5 p.Leu530Arg (OR = 3.62, P = 4.1 x 10(-5)) associating with recurrent kidney stones. We also observe associations of the identified kidney stone variants with biochemical traits in a large population set, indicating potential biological mechanism.

引用

页数：9

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