Genome-Wide Association Study for Renal Traits in the Framingham Heart and Atherosclerosis Risk in Communities StudiesReportar como inadecuado


Genome-Wide Association Study for Renal Traits in the Framingham Heart and Atherosclerosis Risk in Communities Studies


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Citation

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

Abstract

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.Rights

Copyright 2008 Kottgen et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution 2.0 License http:-creativecommons.org-licenses-by-2.0, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

MED: Medicine Papers - SPH Biostatistics Papers - Framingham Heart Study Papers - SPH Epidemiology Papers -



Autor: Kottgen, Anna - Kao, Wen Hong L. - Hwang, Shih-Jen - Boerwinkle, Eric - Yang, Qiong - Levy, Daniel - Benjamin, Emelia J. - Larson

Fuente: https://open.bu.edu/







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