Meta-analysis of genome-wide association studies identifies two loci associated with circulating osteoprotegerin levels
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Osteoprotegerin (OPG) is involved in bone homeostasis and tumor cell survival. Circulating OPG levels are also important biomarkers of various clinical traits, such as cancers and atherosclerosis. OPG levels were measured in serum or in plasma. In a meta-analysis of genome-wide association studies in up to 10 336 individuals from European and Asian origin, we discovered that variants >100 kb upstream of the TNFRSF11B gene encoding OPG and another new locus on chromosome 17q11.2 were significantly associated with OPG variation. We also identified a suggestive locus on chromosome 14q21.2 associated with the trait. Moreover, we estimated that over half of the heritability of OPG levels could be explained by all variants examined in our study. Our findings provide further insight into the genetic regulation of circulating OPG levels.
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Teumer A; Tin A; Sorice R; Gorski M; Yeo NC; Chu AY; Li M; Li Y; Mijatovic V; Ko YA; Taliun D; Luciani A; Chen MH; Yang Q; Foster MC; Olden M; Hiraki LT; Tayo BO; Fuchsberger C; Dieffenbach AK; Shuldiner AR; Smith AV; Zappa AM; Lupo A; Kollerits B; Ponte B; Stengel B; Krämer BK; Paulweber B; Mitchell BD; Hayward C; Helmer C; Meisinger C; Gieger C; Shaffer CM; Müller C; Langenberg C; Ackermann D; Siscovick D; DCCT/EDIC; Boerwinkle E; Kronenberg F; Ehret GB; Homuth G; Waeber G; Navis G; Gambaro G; Malerba G; Eiriksdottir G; Li G; Wichmann HE; Grallert H; Wallaschofski H; Völzke H; Brenner H; Kramer H; Mateo Leach I; Rudan I; Hillege HL; Beckmann JS; Lambert JC; Luan J; Zhao JH; Chalmers J; Coresh J; Denny JC; Butterbach K; Launer LJ; Ferrucci L; Kedenko L; Haun M; Metzger M; Woodward M; Hoffman MJ; Nauck M; Waldenberger M; Pruijm M; Bochud M; Rheinberger M; Verweij N; Wareham NJ; Endlich N; Soranzo N; Polasek O; van der Harst P; Pramstaller PP; Vollenweider P; Wild PS; Gansevoort RT; Rettig R; Biffar R; Carroll RJ; Katz R; Loos RJ; Hwang SJ; Coassin S; Bergmann S; Rosas SE; Stracke S; Harris TB; Corre T; Zeller T; Illig T; Aspelund T; Tanaka T; Lendeckel U; Völker U; Gudnason V; Chouraki V; Koenig W; Kutalik Z; O'Connell JR; Parsa A; Heid IM; Paterson AD; de Boer IH; Devuyst O; Lazar J; Endlich K; Susztak K; Tremblay J; Hamet P; Jacob HJ; Böger CA; Fox CS; Pattaro C; Köttgen A (2016)Elevated concentrations of albumin in the urine, albuminuria, are a hallmark of diabetic kidney disease and are associated with an increased risk for end-stage renal disease and cardiovascular events. To gain insight into ...
Common variants in the JAZF1 gene associated with height identified by linkage and genome-wide association analysis Johansson A; Marroni F; Hayward C; Franklin CS; Kirichenko AV; Jonasson I; Hicks AA; Vitart V; Isaacs A; Axenovich T; Campbell S; Dunlop MG; Floyd J; Hastie N; Hofman A; Knott S; Kolcic I; Pichler I; Polasek O; Rivadeneira F; Tenesa A; Uitterlinden AG; Wild SH; Zorkoltseva IV; Meitinger T; Wilson JF; Rudan I; Campbell H; Pattaro C; Pramstaller P; Oostra BA; Wright AF; van Duijn CM; Aulchenko YS; Gyllensten U; EUROSPAN Consortium (2009)Genes for height have gained interest for decades, but only recently have candidate genes started to be identified. We have performed linkage analysis and genome-wide association for height in approximately 4000 individuals ...
Combination of mouse models and genomewide association studies highlights novel genes associated with human kidney function Jing J; Pattaro C; Hoppmann A; Okada Y; CKDGen Consortium; Fox CS; Köttgen A (2016)Genomewide association studies have identified numerous chronic kidney disease-associated genetic variants, but often do not pinpoint causal genes. This limitation was addressed by combining Mouse Genome Informatics ...