Please use this identifier to cite or link to this item: http://dl.umsu.ac.ir/handle/2144/2515
Title: Genome-Wide Association Study for Renal Traits in the Framingham Heart and Atherosclerosis Risk in Communities Studies
Authors: Kottgen, Anna;Kao, Wen Hong L;Hwang, Shih-Jen;Boerwinkle, Eric;Yang, Qiong;Levy, Daniel;Benjamin, Emelia J;Larson, Martin G;Astor, Brad C;Coresh, Josef;Fox, Caroline S
Year: 2008
3-Jun-2008
Publisher: BioMed Central
Description: BACKGROUND: The Framingham Heart Study (FHS) recently obtained initial results from the first genome-wide association scan for renal traits. The study of 70,987 single nucleotide polymorphisms (SNPs) in 1,010 FHS participants provides a list of SNPs showing the strongest associations with renal traits which need to be verified in independent study samples. METHODS: Sixteen SNPs were selected for replication based on the most promising associations with chronic kidney disease (CKD), estimated glomerular filtration rate (eGFR), and serum cystatin C in FHS. These SNPs were genotyped in 15,747 participants of the Atherosclerosis in Communities (ARIC) Study and evaluated for association using multivariable adjusted regression analyses. Primary outcomes in ARIC were CKD and eGFR. Secondary prospective analyses were conducted for association with kidney disease progression using multivariable adjusted Cox proportional hazards regression. The definition of the outcomes, all covariates, and the use of an additive genetic model was consistent with the original analyses in FHS. RESULTS: The intronic SNP rs6495446 in the gene MTHFS was significantly associated with CKD among white ARIC participants at visit 4: the odds ratio per each C allele was 1.24 (95% CI 1.09–1.41, p = 0.001). Borderline significant associations of rs6495446 were observed with CKD at study visit 1 (p = 0.024), eGFR at study visits 1 (p = 0.073) and 4 (lower mean eGFR per C allele by 0.6 ml/min/1.73 m2, p = 0.043) and kidney disease progression (hazard ratio 1.13 per each C allele, 95% CI 1.00–1.26, p = 0.041). Another SNP, rs3779748 in EYA1, was significantly associated with CKD at ARIC visit 1 (odds ratio per each T allele 1.22, p = 0.01), but only with eGFR and cystatin C in FHS. CONCLUSION: This genome-wide association study provides unbiased information implicating MTHFS as a candidate gene for kidney disease. Our findings highlight the importance of replication to identify common SNPs associated with renal traits.
National Heart, Lung, and Blood Institute's Framingham Heart Study (N01-HC-25195); National Heart, Lung, and Blood Institute (N01-HC55015, N01-HC-55016, N01-HC-55018, N01-HC-55019, N01-HC-55020, N01-HC-55021, N01-HC-55022); Germam Research Foundation Fellowship; National Institutes of Health (K01DK067207)
URI: http://creativecommons.org/licenses/by/2.0
http://open.bu.edu/handle/2144/2515
Standard no: Kottgen, Anna, Wen Hong L Kao, Shih-Jen Hwang, Eric Boerwinkle, Qiong Yang, Daniel Levy, Emelia J Benjamin, Martin G Larson, Brad C Astor, Josef Coresh, Caroline S Fox. "Genome-wide association study for renal traits in the Framingham Heart and Atherosclerosis Risk in Communities Studies" BMC Medical Genetics 9:49. (2008)
1471-2350
10.1186/1471-2350-9-49
18522750
2430944
Appears in Collections:School of Medicine

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