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10.1016/j.ajhg.2016.07.012 http://scihub22266oqcxt.onion/10.1016/j.ajhg.2016.07.012 C5011075!5011075!27588450     free     free     free Deprecated: Implicit conversion from float 231.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 231.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 231.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 231.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 231.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534       Am+J+Hum+Genet 2016 ; 99 (3): 636-46 Nephropedia Template TP {{tp|p=27588450|t=2016. Trans-ethnic Fine Mapping Highlights Kidney-Function Genes Linked to Salt Sensitivity |pdf=|usr=}}{{27588450}} gab.com Text Trans-ethnic Fine Mapping Highlights Kidney-Function Genes Linked to Salt Sensitivity JO: Am J Hum Genet http://www.kidney.de/pget.php?&tw=1&pmid=27588450 #FOAvip We analyzed genome-wide association studies (GWASs), including data from 71,638 individuals from four ancestries, for estimated glomerular filtration rate (eGFR), a measure of kidney function used to define chronic kidney disease (CKD). We identified 20 loci attaining genome-wide-significant evidence of association (p < 5 × 10?8) with kidney function and highlighted that allelic effects on eGFR at lead SNPs are homogeneous across ancestries. We leveraged differences in the pattern of linkage disequilibrium between diverse populations to fine-map the 20 loci through construction of ?credible sets? of variants driving eGFR association signals. Credible variants at the 20 eGFR loci were enriched for DNase I hypersensitivity sites (DHSs) in human kidney cells. DHS credible variants were expression quantitative trait loci for NFATC1 and RGS14 (at the SLC34A1 locus) in multiple tissues. Loss-of-function mutations in ancestral orthologs of both genes in Drosophila melanogaster were associated with altered sensitivity to salt stress. Renal mRNA expression of Nfatc1 and Rgs14 in a salt-sensitive mouse model was also reduced after exposure to a high-salt diet or induced CKD. Our study (1) demonstrates the utility of trans-ethnic fine mapping through integration of GWASs involving diverse populations with genomic annotation from relevant tissues to define molecular mechanisms by which association signals exert their effect and (2) suggests that salt sensitivity might be an important marker for biological processes that affect kidney function and CKD in humans. Twit Text FOAVip Trans-ethnic Fine Mapping Highlights Kidney-Function Genes Linked to Salt Sensitivity ????Am J Hum Genet http://www.kidney.de/pget.php?&tw=1&pmid=27588450 #FOAvip Twit Text # Free Paper on # # # # # LINK http://www.kidney.de/pget.php?&tw=1&pmid=27588450 #FOAvip English Wikipedia <ref>{{Cite pmid|27588450}}</ref> Trans-ethnic Fine Mapping Highlights Kidney-Function Genes Linked to Salt Sensitivity #MMPMID27588450 Mahajan A; Rodan A; Le T; Gaulton K; Haessler J; Stilp A; Kamatani Y; Zhu G; Sofer T; Puri S; Schellinger J; Chu PL; Cechova S; van Zuydam N; Arnlov J; Flessner M; Giedraitis V; Heath A; Kubo M; Larsson A; Lindgren C; Madden P; Montgomery G; Papanicolaou G; Reiner A; Sundström J; Thornton T; Lind L; Ingelsson E; Cai J; Martin N; Kooperberg C; Matsuda K; Whitfield J; Okada Y; Laurie C; Morris A; Franceschini N Am J Hum Genet 2016[Sep]; 99 (3): 636-46 PMID27588450show ga We analyzed genome-wide association studies (GWASs), including data from 71,638 individuals from four ancestries, for estimated glomerular filtration rate (eGFR), a measure of kidney function used to define chronic kidney disease (CKD). We identified 20 loci attaining genome-wide-significant evidence of association (p < 5 × 10?8) with kidney function and highlighted that allelic effects on eGFR at lead SNPs are homogeneous across ancestries. We leveraged differences in the pattern of linkage disequilibrium between diverse populations to fine-map the 20 loci through construction of ?credible sets? of variants driving eGFR association signals. Credible variants at the 20 eGFR loci were enriched for DNase I hypersensitivity sites (DHSs) in human kidney cells. DHS credible variants were expression quantitative trait loci for NFATC1 and RGS14 (at the SLC34A1 locus) in multiple tissues. Loss-of-function mutations in ancestral orthologs of both genes in Drosophila melanogaster were associated with altered sensitivity to salt stress. Renal mRNA expression of Nfatc1 and Rgs14 in a salt-sensitive mouse model was also reduced after exposure to a high-salt diet or induced CKD. Our study (1) demonstrates the utility of trans-ethnic fine mapping through integration of GWASs involving diverse populations with genomic annotation from relevant tissues to define molecular mechanisms by which association signals exert their effect and (2) suggests that salt sensitivity might be an important marker for biological processes that affect kidney function and CKD in humans. äTrans-ethnic Fine Mapping Highlights Kidney-Function Genes Linked to S(epmc).pdf DeepDyve Pubget Overpricing