Genetic association analyses of non-synonymous single nucleotide polymorphisms in diabetic nephropathy

D.A. Savage; C.C. Patterson; P. Deloukas; P. Whittaker; A.J. McKnight; J. Morrison; A.J. Boulton; A.G. Demaine; S.M. Marshall; B.A. Millward; S.M. Thomas; G.C. Viberti; J.D. Walker; D. Sadlier; A.P. Maxwell; S.C. Bain

doi:10.1007/s00125-008-1142-5

Genetic association analyses of non-synonymous single nucleotide polymorphisms in diabetic nephropathy

D.A. Savage, C.C. Patterson, P. Deloukas, P. Whittaker, A.J. McKnight, J. Morrison, A.J. Boulton, A.G. Demaine, S.M. Marshall, B.A. Millward, S.M. Thomas, G.C. Viberti, J.D. Walker, D. Sadlier, A.P. Maxwell, S.C. Bain

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Abstract

Aims/hypothesis: Diabetic nephropathy, characterised by persistent proteinuria, hypertension and progressive kidney failure, affects a subset of susceptible individuals with diabetes. It is also a leading cause of end-stage renal disease (ESRD). Non-synonymous (ns) single nucleotide polymorphisms (SNPs) have been reported to contribute to genetic susceptibility in both monogenic disorders and common complex diseases. The objective of this study was to investigate whether nsSNPs are involved in susceptibility to diabetic nephropathy using a case-control design.

Methods: White type 1 diabetic patients with (cases) and without (controls) nephropathy from eight centres in the UK and Ireland were genotyped for a selected subset of nsSNPs using Illumina's GoldenGate BeadArray assay. A ? 2 test for trend, stratified by centre, was used to assess differences in genotype distribution between cases and controls. Genomic control was used to adjust for possible inflation of test statistics, and the False Discovery Rate method was used to account for multiple testing.

Results: We assessed 1,111 nsSNPs for association with diabetic nephropathy in 1,711 individuals with type 1 diabetes (894 cases, 817 controls). A number of SNPs demonstrated a significant difference in genotype distribution between groups before but not after correction for multiple testing. Furthermore, neither subgroup analysis (diabetic nephropathy with ESRD or diabetic nephropathy without ESRD) nor stratification by duration of diabetes revealed any significant differences between groups.

Conclusions/interpretation: The nsSNPs investigated in this study do not appear to contribute significantly to the development of diabetic nephropathy in patients with type 1 diabetes.

Original language	English
Pages (from-to)	1998-2002
Number of pages	5
Journal	Diabetologia
Volume	51
Issue number	11
DOIs	https://doi.org/10.1007/s00125-008-1142-5
Publication status	Published - Nov 2008

ASJC Scopus subject areas

Internal Medicine
Endocrinology, Diabetes and Metabolism

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1007/s00125-008-1142-5

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Savage, D. A., Patterson, C. C., Deloukas, P., Whittaker, P., McKnight, A. J., Morrison, J., Boulton, A. J., Demaine, A. G., Marshall, S. M., Millward, B. A., Thomas, S. M., Viberti, G. C., Walker, J. D., Sadlier, D., Maxwell, A. P., & Bain, S. C. (2008). Genetic association analyses of non-synonymous single nucleotide polymorphisms in diabetic nephropathy. Diabetologia, 51(11), 1998-2002. https://doi.org/10.1007/s00125-008-1142-5

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title = "Genetic association analyses of non-synonymous single nucleotide polymorphisms in diabetic nephropathy",

abstract = "Aims/hypothesis: Diabetic nephropathy, characterised by persistent proteinuria, hypertension and progressive kidney failure, affects a subset of susceptible individuals with diabetes. It is also a leading cause of end-stage renal disease (ESRD). Non-synonymous (ns) single nucleotide polymorphisms (SNPs) have been reported to contribute to genetic susceptibility in both monogenic disorders and common complex diseases. The objective of this study was to investigate whether nsSNPs are involved in susceptibility to diabetic nephropathy using a case-control design. Methods: White type 1 diabetic patients with (cases) and without (controls) nephropathy from eight centres in the UK and Ireland were genotyped for a selected subset of nsSNPs using Illumina's GoldenGate BeadArray assay. A ? 2 test for trend, stratified by centre, was used to assess differences in genotype distribution between cases and controls. Genomic control was used to adjust for possible inflation of test statistics, and the False Discovery Rate method was used to account for multiple testing. Results: We assessed 1,111 nsSNPs for association with diabetic nephropathy in 1,711 individuals with type 1 diabetes (894 cases, 817 controls). A number of SNPs demonstrated a significant difference in genotype distribution between groups before but not after correction for multiple testing. Furthermore, neither subgroup analysis (diabetic nephropathy with ESRD or diabetic nephropathy without ESRD) nor stratification by duration of diabetes revealed any significant differences between groups.Conclusions/interpretation: The nsSNPs investigated in this study do not appear to contribute significantly to the development of diabetic nephropathy in patients with type 1 diabetes. ",

author = "D.A. Savage and C.C. Patterson and P. Deloukas and P. Whittaker and A.J. McKnight and J. Morrison and A.J. Boulton and A.G. Demaine and S.M. Marshall and B.A. Millward and S.M. Thomas and G.C. Viberti and J.D. Walker and D. Sadlier and A.P. Maxwell and S.C. Bain",

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Savage, DA, Patterson, CC, Deloukas, P, Whittaker, P, McKnight, AJ, Morrison, J, Boulton, AJ, Demaine, AG, Marshall, SM, Millward, BA, Thomas, SM, Viberti, GC, Walker, JD, Sadlier, D, Maxwell, AP & Bain, SC 2008, 'Genetic association analyses of non-synonymous single nucleotide polymorphisms in diabetic nephropathy', Diabetologia, vol. 51, no. 11, pp. 1998-2002. https://doi.org/10.1007/s00125-008-1142-5

TY - JOUR

T1 - Genetic association analyses of non-synonymous single nucleotide polymorphisms in diabetic nephropathy

AU - Savage, D.A.

AU - Patterson, C.C.

AU - Deloukas, P.

AU - Whittaker, P.

AU - McKnight, A.J.

AU - Morrison, J.

AU - Boulton, A.J.

AU - Demaine, A.G.

AU - Marshall, S.M.

AU - Millward, B.A.

AU - Thomas, S.M.

AU - Viberti, G.C.

AU - Walker, J.D.

AU - Sadlier, D.

AU - Maxwell, A.P.

AU - Bain, S.C.

PY - 2008/11

Y1 - 2008/11

N2 - Aims/hypothesis: Diabetic nephropathy, characterised by persistent proteinuria, hypertension and progressive kidney failure, affects a subset of susceptible individuals with diabetes. It is also a leading cause of end-stage renal disease (ESRD). Non-synonymous (ns) single nucleotide polymorphisms (SNPs) have been reported to contribute to genetic susceptibility in both monogenic disorders and common complex diseases. The objective of this study was to investigate whether nsSNPs are involved in susceptibility to diabetic nephropathy using a case-control design. Methods: White type 1 diabetic patients with (cases) and without (controls) nephropathy from eight centres in the UK and Ireland were genotyped for a selected subset of nsSNPs using Illumina's GoldenGate BeadArray assay. A ? 2 test for trend, stratified by centre, was used to assess differences in genotype distribution between cases and controls. Genomic control was used to adjust for possible inflation of test statistics, and the False Discovery Rate method was used to account for multiple testing. Results: We assessed 1,111 nsSNPs for association with diabetic nephropathy in 1,711 individuals with type 1 diabetes (894 cases, 817 controls). A number of SNPs demonstrated a significant difference in genotype distribution between groups before but not after correction for multiple testing. Furthermore, neither subgroup analysis (diabetic nephropathy with ESRD or diabetic nephropathy without ESRD) nor stratification by duration of diabetes revealed any significant differences between groups.Conclusions/interpretation: The nsSNPs investigated in this study do not appear to contribute significantly to the development of diabetic nephropathy in patients with type 1 diabetes.

AB - Aims/hypothesis: Diabetic nephropathy, characterised by persistent proteinuria, hypertension and progressive kidney failure, affects a subset of susceptible individuals with diabetes. It is also a leading cause of end-stage renal disease (ESRD). Non-synonymous (ns) single nucleotide polymorphisms (SNPs) have been reported to contribute to genetic susceptibility in both monogenic disorders and common complex diseases. The objective of this study was to investigate whether nsSNPs are involved in susceptibility to diabetic nephropathy using a case-control design. Methods: White type 1 diabetic patients with (cases) and without (controls) nephropathy from eight centres in the UK and Ireland were genotyped for a selected subset of nsSNPs using Illumina's GoldenGate BeadArray assay. A ? 2 test for trend, stratified by centre, was used to assess differences in genotype distribution between cases and controls. Genomic control was used to adjust for possible inflation of test statistics, and the False Discovery Rate method was used to account for multiple testing. Results: We assessed 1,111 nsSNPs for association with diabetic nephropathy in 1,711 individuals with type 1 diabetes (894 cases, 817 controls). A number of SNPs demonstrated a significant difference in genotype distribution between groups before but not after correction for multiple testing. Furthermore, neither subgroup analysis (diabetic nephropathy with ESRD or diabetic nephropathy without ESRD) nor stratification by duration of diabetes revealed any significant differences between groups.Conclusions/interpretation: The nsSNPs investigated in this study do not appear to contribute significantly to the development of diabetic nephropathy in patients with type 1 diabetes.

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U2 - 10.1007/s00125-008-1142-5

DO - 10.1007/s00125-008-1142-5

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JO - Diabetologia

JF - Diabetologia

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Genetic association analyses of non-synonymous single nucleotide polymorphisms in diabetic nephropathy

Abstract

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