A genome-wide search for linkage of estimated glomerular filtration rate (eGFR) in the Family Investigation of Nephropathy and Diabetes (FIND).
Estimated glomerular filtration rate (eGFR), a measure of kidney function, is heritable, suggesting that genes influence renal function. Genes that influence eGFR have been identified through genome-wide association studies. However, family-based linkage approaches may identify loci that explain a l...
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doaj-918ae96f77ff4b0ead41503b95daf6bf2020-11-25T01:56:05ZengPublic Library of Science (PLoS)PLoS ONE1932-62032013-01-01812e8188810.1371/journal.pone.0081888A genome-wide search for linkage of estimated glomerular filtration rate (eGFR) in the Family Investigation of Nephropathy and Diabetes (FIND).Farook ThameemRobert P IgoBarry I FreedmanCarl LangefeldRobert L HansonJeffrey R SchellingRobert C ElstonRavindranath DuggiralaSusanne B NicholasKatrina A B GoddardJasmin DiversXiuqing GuoEli IppPaul L KimmelLucy A MeoniVallabh O ShahMichael W SmithCheryl A WinklerPhilip G ZagerWilliam C KnowlerRobert G NelsonMadeline V PahlRulan S ParekhW H Linda KaoRebekah S RasoolySharon G AdlerHanna E AbboudSudha K IyengarJohn R SedorFamily Investigation of Nephropathy and Diabetes Research GroupEstimated glomerular filtration rate (eGFR), a measure of kidney function, is heritable, suggesting that genes influence renal function. Genes that influence eGFR have been identified through genome-wide association studies. However, family-based linkage approaches may identify loci that explain a larger proportion of the heritability. This study used genome-wide linkage and association scans to identify quantitative trait loci (QTL) that influence eGFR.Genome-wide linkage and sparse association scans of eGFR were performed in families ascertained by probands with advanced diabetic nephropathy (DN) from the multi-ethnic Family Investigation of Nephropathy and Diabetes (FIND) study. This study included 954 African Americans (AA), 781 American Indians (AI), 614 European Americans (EA) and 1,611 Mexican Americans (MA). A total of 3,960 FIND participants were genotyped for 6,000 single nucleotide polymorphisms (SNPs) using the Illumina Linkage IVb panel. GFR was estimated by the Modification of Diet in Renal Disease (MDRD) formula.The non-parametric linkage analysis, accounting for the effects of diabetes duration and BMI, identified the strongest evidence for linkage of eGFR on chromosome 20q11 (log of the odds [LOD] = 3.34; P = 4.4 × 10(-5)) in MA and chromosome 15q12 (LOD = 2.84; P = 1.5 × 10(-4)) in EA. In all subjects, the strongest linkage signal for eGFR was detected on chromosome 10p12 (P = 5.5 × 10(-4)) at 44 cM near marker rs1339048. A subsequent association scan in both ancestry-specific groups and the entire population identified several SNPs significantly associated with eGFR across the genome.The present study describes the localization of QTL influencing eGFR on 20q11 in MA, 15q21 in EA and 10p12 in the combined ethnic groups participating in the FIND study. Identification of causal genes/variants influencing eGFR, within these linkage and association loci, will open new avenues for functional analyses and development of novel diagnostic markers for DN.http://europepmc.org/articles/PMC3866106?pdf=render |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Farook Thameem Robert P Igo Barry I Freedman Carl Langefeld Robert L Hanson Jeffrey R Schelling Robert C Elston Ravindranath Duggirala Susanne B Nicholas Katrina A B Goddard Jasmin Divers Xiuqing Guo Eli Ipp Paul L Kimmel Lucy A Meoni Vallabh O Shah Michael W Smith Cheryl A Winkler Philip G Zager William C Knowler Robert G Nelson Madeline V Pahl Rulan S Parekh W H Linda Kao Rebekah S Rasooly Sharon G Adler Hanna E Abboud Sudha K Iyengar John R Sedor Family Investigation of Nephropathy and Diabetes Research Group |
spellingShingle |
Farook Thameem Robert P Igo Barry I Freedman Carl Langefeld Robert L Hanson Jeffrey R Schelling Robert C Elston Ravindranath Duggirala Susanne B Nicholas Katrina A B Goddard Jasmin Divers Xiuqing Guo Eli Ipp Paul L Kimmel Lucy A Meoni Vallabh O Shah Michael W Smith Cheryl A Winkler Philip G Zager William C Knowler Robert G Nelson Madeline V Pahl Rulan S Parekh W H Linda Kao Rebekah S Rasooly Sharon G Adler Hanna E Abboud Sudha K Iyengar John R Sedor Family Investigation of Nephropathy and Diabetes Research Group A genome-wide search for linkage of estimated glomerular filtration rate (eGFR) in the Family Investigation of Nephropathy and Diabetes (FIND). PLoS ONE |
author_facet |
Farook Thameem Robert P Igo Barry I Freedman Carl Langefeld Robert L Hanson Jeffrey R Schelling Robert C Elston Ravindranath Duggirala Susanne B Nicholas Katrina A B Goddard Jasmin Divers Xiuqing Guo Eli Ipp Paul L Kimmel Lucy A Meoni Vallabh O Shah Michael W Smith Cheryl A Winkler Philip G Zager William C Knowler Robert G Nelson Madeline V Pahl Rulan S Parekh W H Linda Kao Rebekah S Rasooly Sharon G Adler Hanna E Abboud Sudha K Iyengar John R Sedor Family Investigation of Nephropathy and Diabetes Research Group |
author_sort |
Farook Thameem |
title |
A genome-wide search for linkage of estimated glomerular filtration rate (eGFR) in the Family Investigation of Nephropathy and Diabetes (FIND). |
title_short |
A genome-wide search for linkage of estimated glomerular filtration rate (eGFR) in the Family Investigation of Nephropathy and Diabetes (FIND). |
title_full |
A genome-wide search for linkage of estimated glomerular filtration rate (eGFR) in the Family Investigation of Nephropathy and Diabetes (FIND). |
title_fullStr |
A genome-wide search for linkage of estimated glomerular filtration rate (eGFR) in the Family Investigation of Nephropathy and Diabetes (FIND). |
title_full_unstemmed |
A genome-wide search for linkage of estimated glomerular filtration rate (eGFR) in the Family Investigation of Nephropathy and Diabetes (FIND). |
title_sort |
genome-wide search for linkage of estimated glomerular filtration rate (egfr) in the family investigation of nephropathy and diabetes (find). |
publisher |
Public Library of Science (PLoS) |
series |
PLoS ONE |
issn |
1932-6203 |
publishDate |
2013-01-01 |
description |
Estimated glomerular filtration rate (eGFR), a measure of kidney function, is heritable, suggesting that genes influence renal function. Genes that influence eGFR have been identified through genome-wide association studies. However, family-based linkage approaches may identify loci that explain a larger proportion of the heritability. This study used genome-wide linkage and association scans to identify quantitative trait loci (QTL) that influence eGFR.Genome-wide linkage and sparse association scans of eGFR were performed in families ascertained by probands with advanced diabetic nephropathy (DN) from the multi-ethnic Family Investigation of Nephropathy and Diabetes (FIND) study. This study included 954 African Americans (AA), 781 American Indians (AI), 614 European Americans (EA) and 1,611 Mexican Americans (MA). A total of 3,960 FIND participants were genotyped for 6,000 single nucleotide polymorphisms (SNPs) using the Illumina Linkage IVb panel. GFR was estimated by the Modification of Diet in Renal Disease (MDRD) formula.The non-parametric linkage analysis, accounting for the effects of diabetes duration and BMI, identified the strongest evidence for linkage of eGFR on chromosome 20q11 (log of the odds [LOD] = 3.34; P = 4.4 × 10(-5)) in MA and chromosome 15q12 (LOD = 2.84; P = 1.5 × 10(-4)) in EA. In all subjects, the strongest linkage signal for eGFR was detected on chromosome 10p12 (P = 5.5 × 10(-4)) at 44 cM near marker rs1339048. A subsequent association scan in both ancestry-specific groups and the entire population identified several SNPs significantly associated with eGFR across the genome.The present study describes the localization of QTL influencing eGFR on 20q11 in MA, 15q21 in EA and 10p12 in the combined ethnic groups participating in the FIND study. Identification of causal genes/variants influencing eGFR, within these linkage and association loci, will open new avenues for functional analyses and development of novel diagnostic markers for DN. |
url |
http://europepmc.org/articles/PMC3866106?pdf=render |
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