Genetic association for renal traits among participants of African ancestry reveals new loci for renal function.
Chronic kidney disease (CKD) is an increasing global public health concern, particularly among populations of African ancestry. We performed an interrogation of known renal loci, genome-wide association (GWA), and IBC candidate-gene SNP association analyses in African Americans from the CARe Renal C...
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2011
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oai:doaj.org-article:d2c28706d3414cd8802d198b619c03b12021-11-04T06:01:50ZGenetic association for renal traits among participants of African ancestry reveals new loci for renal function.1553-73901553-740410.1371/journal.pgen.1002264https://doaj.org/article/d2c28706d3414cd8802d198b619c03b12011-09-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/21931561/?tool=EBIhttps://doaj.org/toc/1553-7390https://doaj.org/toc/1553-7404Chronic kidney disease (CKD) is an increasing global public health concern, particularly among populations of African ancestry. We performed an interrogation of known renal loci, genome-wide association (GWA), and IBC candidate-gene SNP association analyses in African Americans from the CARe Renal Consortium. In up to 8,110 participants, we performed meta-analyses of GWA and IBC array data for estimated glomerular filtration rate (eGFR), CKD (eGFR <60 mL/min/1.73 m(2)), urinary albumin-to-creatinine ratio (UACR), and microalbuminuria (UACR >30 mg/g) and interrogated the 250 kb flanking region around 24 SNPs previously identified in European Ancestry renal GWAS analyses. Findings were replicated in up to 4,358 African Americans. To assess function, individually identified genes were knocked down in zebrafish embryos by morpholino antisense oligonucleotides. Expression of kidney-specific genes was assessed by in situ hybridization, and glomerular filtration was evaluated by dextran clearance. Overall, 23 of 24 previously identified SNPs had direction-consistent associations with eGFR in African Americans, 2 of which achieved nominal significance (UMOD, PIP5K1B). Interrogation of the flanking regions uncovered 24 new index SNPs in African Americans, 12 of which were replicated (UMOD, ANXA9, GCKR, TFDP2, DAB2, VEGFA, ATXN2, GATM, SLC22A2, TMEM60, SLC6A13, and BCAS3). In addition, we identified 3 suggestive loci at DOK6 (p-value = 5.3×10(-7)) and FNDC1 (p-value = 3.0×10(-7)) for UACR, and KCNQ1 with eGFR (p = 3.6×10(-6)). Morpholino knockdown of kcnq1 in the zebrafish resulted in abnormal kidney development and filtration capacity. We identified several SNPs in association with eGFR in African Ancestry individuals, as well as 3 suggestive loci for UACR and eGFR. Functional genetic studies support a role for kcnq1 in glomerular development in zebrafish.Ching-Ti LiuMaija K GarnaasAdrienne TinAnna KottgenNora FranceschiniCarmen A PeraltaIan H de BoerXiaoning LuElizabeth AtkinsonJingzhong DingMichael NallsDaniel ShrinerJosef CoreshAbdullah KutlarKirsten Bibbins-DomingoDavid SiscovickErmeg AkylbekovaSharon WyattBrad AstorJosef MychaleckjyMan LiMuredach P ReillyRaymond R TownsendAdebowale AdeyemoAlan B ZondermanMariza de AndradeStephen T TurnerThomas H MosleyTamara B HarrisCKDGen ConsortiumCharles N RotimiYongmei LiuSharon L R KardiaMichele K EvansMichael G ShlipakHolly KramerMichael F FlessnerAlbert W DreisbachWolfram GoesslingL Adrienne CupplesW Linda KaoCaroline S FoxPublic Library of Science (PLoS)articleGeneticsQH426-470ENPLoS Genetics, Vol 7, Iss 9, p e1002264 (2011) |
| institution |
DOAJ |
| collection |
DOAJ |
| language |
EN |
| topic |
Genetics QH426-470 |
| spellingShingle |
Genetics QH426-470 Ching-Ti Liu Maija K Garnaas Adrienne Tin Anna Kottgen Nora Franceschini Carmen A Peralta Ian H de Boer Xiaoning Lu Elizabeth Atkinson Jingzhong Ding Michael Nalls Daniel Shriner Josef Coresh Abdullah Kutlar Kirsten Bibbins-Domingo David Siscovick Ermeg Akylbekova Sharon Wyatt Brad Astor Josef Mychaleckjy Man Li Muredach P Reilly Raymond R Townsend Adebowale Adeyemo Alan B Zonderman Mariza de Andrade Stephen T Turner Thomas H Mosley Tamara B Harris CKDGen Consortium Charles N Rotimi Yongmei Liu Sharon L R Kardia Michele K Evans Michael G Shlipak Holly Kramer Michael F Flessner Albert W Dreisbach Wolfram Goessling L Adrienne Cupples W Linda Kao Caroline S Fox Genetic association for renal traits among participants of African ancestry reveals new loci for renal function. |
| description |
Chronic kidney disease (CKD) is an increasing global public health concern, particularly among populations of African ancestry. We performed an interrogation of known renal loci, genome-wide association (GWA), and IBC candidate-gene SNP association analyses in African Americans from the CARe Renal Consortium. In up to 8,110 participants, we performed meta-analyses of GWA and IBC array data for estimated glomerular filtration rate (eGFR), CKD (eGFR <60 mL/min/1.73 m(2)), urinary albumin-to-creatinine ratio (UACR), and microalbuminuria (UACR >30 mg/g) and interrogated the 250 kb flanking region around 24 SNPs previously identified in European Ancestry renal GWAS analyses. Findings were replicated in up to 4,358 African Americans. To assess function, individually identified genes were knocked down in zebrafish embryos by morpholino antisense oligonucleotides. Expression of kidney-specific genes was assessed by in situ hybridization, and glomerular filtration was evaluated by dextran clearance. Overall, 23 of 24 previously identified SNPs had direction-consistent associations with eGFR in African Americans, 2 of which achieved nominal significance (UMOD, PIP5K1B). Interrogation of the flanking regions uncovered 24 new index SNPs in African Americans, 12 of which were replicated (UMOD, ANXA9, GCKR, TFDP2, DAB2, VEGFA, ATXN2, GATM, SLC22A2, TMEM60, SLC6A13, and BCAS3). In addition, we identified 3 suggestive loci at DOK6 (p-value = 5.3×10(-7)) and FNDC1 (p-value = 3.0×10(-7)) for UACR, and KCNQ1 with eGFR (p = 3.6×10(-6)). Morpholino knockdown of kcnq1 in the zebrafish resulted in abnormal kidney development and filtration capacity. We identified several SNPs in association with eGFR in African Ancestry individuals, as well as 3 suggestive loci for UACR and eGFR. Functional genetic studies support a role for kcnq1 in glomerular development in zebrafish. |
| format |
article |
| author |
Ching-Ti Liu Maija K Garnaas Adrienne Tin Anna Kottgen Nora Franceschini Carmen A Peralta Ian H de Boer Xiaoning Lu Elizabeth Atkinson Jingzhong Ding Michael Nalls Daniel Shriner Josef Coresh Abdullah Kutlar Kirsten Bibbins-Domingo David Siscovick Ermeg Akylbekova Sharon Wyatt Brad Astor Josef Mychaleckjy Man Li Muredach P Reilly Raymond R Townsend Adebowale Adeyemo Alan B Zonderman Mariza de Andrade Stephen T Turner Thomas H Mosley Tamara B Harris CKDGen Consortium Charles N Rotimi Yongmei Liu Sharon L R Kardia Michele K Evans Michael G Shlipak Holly Kramer Michael F Flessner Albert W Dreisbach Wolfram Goessling L Adrienne Cupples W Linda Kao Caroline S Fox |
| author_facet |
Ching-Ti Liu Maija K Garnaas Adrienne Tin Anna Kottgen Nora Franceschini Carmen A Peralta Ian H de Boer Xiaoning Lu Elizabeth Atkinson Jingzhong Ding Michael Nalls Daniel Shriner Josef Coresh Abdullah Kutlar Kirsten Bibbins-Domingo David Siscovick Ermeg Akylbekova Sharon Wyatt Brad Astor Josef Mychaleckjy Man Li Muredach P Reilly Raymond R Townsend Adebowale Adeyemo Alan B Zonderman Mariza de Andrade Stephen T Turner Thomas H Mosley Tamara B Harris CKDGen Consortium Charles N Rotimi Yongmei Liu Sharon L R Kardia Michele K Evans Michael G Shlipak Holly Kramer Michael F Flessner Albert W Dreisbach Wolfram Goessling L Adrienne Cupples W Linda Kao Caroline S Fox |
| author_sort |
Ching-Ti Liu |
| title |
Genetic association for renal traits among participants of African ancestry reveals new loci for renal function. |
| title_short |
Genetic association for renal traits among participants of African ancestry reveals new loci for renal function. |
| title_full |
Genetic association for renal traits among participants of African ancestry reveals new loci for renal function. |
| title_fullStr |
Genetic association for renal traits among participants of African ancestry reveals new loci for renal function. |
| title_full_unstemmed |
Genetic association for renal traits among participants of African ancestry reveals new loci for renal function. |
| title_sort |
genetic association for renal traits among participants of african ancestry reveals new loci for renal function. |
| publisher |
Public Library of Science (PLoS) |
| publishDate |
2011 |
| url |
https://doaj.org/article/d2c28706d3414cd8802d198b619c03b1 |
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