Candidate Gene Association Study for Diabetic Retinopathy in Persons with Type 2 Diabetes: The Candidate Gene Association Resource (CARe)

Lucia Sobrin; Todd Green; Xueling Sim; Richard A. Jensen; E. Shyong Tai; Wan Ting Tay; Jie Jin Wang; Paul Mitchell; Niina Sandholm; Yiyuan Liu; Kustaa Hietala; Sudha K. Iyengar; Matthew Brooks; Monika Buraczynska; Natalie Van Zuydam; Albert V. Smith; Vilmundur Gudnason; Alex S. F. Doney; Andrew D. Morris; Graham P. Leese; Colin N. A. Palmer; Anand Swaroop; Herman A. Taylor; James G. Wilson; Alan Penman; Ching J. Chen; Per-Henrik Groop; Seang-Mei Saw; Tin Aung; Barbara E. Klein; Jerome I. Rotter; David S. Siscovick; Mary Frances Cotch; Ronald Klein; Mark J. Daly; Tien Y. Wong; Wellcome Trust Case Control Consor, Family Invest Nephropathy Diabet-E

doi:10.1167/iovs.11-7510

Candidate Gene Association Study for Diabetic Retinopathy in Persons with Type 2 Diabetes: The Candidate Gene Association Resource (CARe)

Lucia Sobrin, Todd Green, Xueling Sim, Richard A. Jensen, E. Shyong Tai, Wan Ting Tay, Jie Jin Wang, Paul Mitchell, Niina Sandholm, Yiyuan Liu, Kustaa Hietala, Sudha K. Iyengar, Matthew Brooks, Monika Buraczynska, Natalie Van Zuydam, Albert V. Smith, Vilmundur Gudnason, Alex S. F. Doney, Andrew D. Morris, Graham P. LeeseColin N. A. Palmer, Anand Swaroop, Herman A. Taylor, James G. Wilson, Alan Penman, Ching J. Chen, Per-Henrik Groop, Seang-Mei Saw, Tin Aung, Barbara E. Klein, Jerome I. Rotter, David S. Siscovick, Mary Frances Cotch, Ronald Klein, Mark J. Daly, Tien Y. Wong, Wellcome Trust Case Control Consor, Family Invest Nephropathy Diabet-E

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Abstract

PURPOSE. To investigate whether variants in cardiovascular candidate genes, some of which have been previously associated with type 2 diabetes (T2D), diabetic retinopathy (DR), and diabetic nephropathy (DN), are associated with DR in the Candidate gene Association Resource (CARe).

METHODS. Persons with T2D who were enrolled in the study (n = 2691) had fundus photography and genotyping of single nucleotide polymorphisms (SNPs) in 2000 candidate genes. Two case definitions were investigated: Early Treatment Diabetic Retinopathy Study (ETDRS) grades >= 14 and >= 30. The chi(2) analyses for each CARe cohort were combined by Cochran-Mantel- Haenszel (CMH) pooling of odds ratios (ORs) and corrected for multiple hypothesis testing. Logistic regression was performed with adjustment for other DR risk factors. Results from replication in independent cohorts were analyzed with CMH meta-analysis methods.

RESULTS. Among 39 genes previously associated with DR, DN, or T2D, three SNPs in P-selectin (SELP) were associated with DR. The strongest association was to rs6128 (OR = 0.43, P = 0.0001, after Bonferroni correction). These associations remained significant after adjustment for DR risk factors. Among other genes examined, several variants were associated with DR with significant P values, including rs6856425 tagging alpha-Liduronidase (IDUA) (P = 2.1 X 10(-5), after Bonferroni correction). However, replication in independent cohorts did not reveal study-wide significant effects. The P values after replication were 0.55 and 0.10 for rs6128 and rs6856425, respectively.

CONCLUSIONS. Genes associated with DN, T2D, and vascular diseases do not appear to be consistently associated with DR. A few genetic variants associated with DR, particularly those in SELP and near IDUA, should be investigated in additional DR cohorts. (Invest Ophthalmol Vis Sci. 2011;52:7593-7602) DOI:10.1167/iovs.11-7510

Original language	English
Pages (from-to)	7593-7602
Number of pages	10
Journal	Investigative Ophthalmology & Visual Science
Volume	52
Issue number	10
DOIs	https://doi.org/10.1167/iovs.11-7510
Publication status	Published - Sept 2011

Keywords

GENOME-WIDE ASSOCIATION
CORONARY-ARTERY-DISEASE
COMMON VARIANTS
RISK-FACTORS
ERYTHROPOIETIN GENE
LINKAGE ANALYSES
BLOOD-PRESSURE
UNITED-STATES
FTO GENE
COMPLICATIONS

UN SDGs

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

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10.1167/iovs.11-7510

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Sobrin, L., Green, T., Sim, X., Jensen, R. A., Tai, E. S., Tay, W. T., Wang, J. J., Mitchell, P., Sandholm, N., Liu, Y., Hietala, K., Iyengar, S. K., Brooks, M., Buraczynska, M., Van Zuydam, N., Smith, A. V., Gudnason, V., Doney, A. S. F., Morris, A. D., ... Wellcome Trust Case Control Consor, Family Invest Nephropathy Diabet-E (2011). Candidate Gene Association Study for Diabetic Retinopathy in Persons with Type 2 Diabetes: The Candidate Gene Association Resource (CARe). Investigative Ophthalmology & Visual Science, 52(10), 7593-7602. https://doi.org/10.1167/iovs.11-7510

@article{1bbc31c76430404fbc9679441f00362d,

title = "Candidate Gene Association Study for Diabetic Retinopathy in Persons with Type 2 Diabetes: The Candidate Gene Association Resource (CARe)",

abstract = "PURPOSE. To investigate whether variants in cardiovascular candidate genes, some of which have been previously associated with type 2 diabetes (T2D), diabetic retinopathy (DR), and diabetic nephropathy (DN), are associated with DR in the Candidate gene Association Resource (CARe).METHODS. Persons with T2D who were enrolled in the study (n = 2691) had fundus photography and genotyping of single nucleotide polymorphisms (SNPs) in 2000 candidate genes. Two case definitions were investigated: Early Treatment Diabetic Retinopathy Study (ETDRS) grades >= 14 and >= 30. The chi(2) analyses for each CARe cohort were combined by Cochran-Mantel- Haenszel (CMH) pooling of odds ratios (ORs) and corrected for multiple hypothesis testing. Logistic regression was performed with adjustment for other DR risk factors. Results from replication in independent cohorts were analyzed with CMH meta-analysis methods.RESULTS. Among 39 genes previously associated with DR, DN, or T2D, three SNPs in P-selectin (SELP) were associated with DR. The strongest association was to rs6128 (OR = 0.43, P = 0.0001, after Bonferroni correction). These associations remained significant after adjustment for DR risk factors. Among other genes examined, several variants were associated with DR with significant P values, including rs6856425 tagging alpha-Liduronidase (IDUA) (P = 2.1 X 10(-5), after Bonferroni correction). However, replication in independent cohorts did not reveal study-wide significant effects. The P values after replication were 0.55 and 0.10 for rs6128 and rs6856425, respectively.CONCLUSIONS. Genes associated with DN, T2D, and vascular diseases do not appear to be consistently associated with DR. A few genetic variants associated with DR, particularly those in SELP and near IDUA, should be investigated in additional DR cohorts. (Invest Ophthalmol Vis Sci. 2011;52:7593-7602) DOI:10.1167/iovs.11-7510",

keywords = "GENOME-WIDE ASSOCIATION, CORONARY-ARTERY-DISEASE, COMMON VARIANTS, RISK-FACTORS, ERYTHROPOIETIN GENE, LINKAGE ANALYSES, BLOOD-PRESSURE, UNITED-STATES, FTO GENE, COMPLICATIONS",

author = "Lucia Sobrin and Todd Green and Xueling Sim and Jensen, {Richard A.} and Tai, {E. Shyong} and Tay, {Wan Ting} and Wang, {Jie Jin} and Paul Mitchell and Niina Sandholm and Yiyuan Liu and Kustaa Hietala and Iyengar, {Sudha K.} and Matthew Brooks and Monika Buraczynska and {Van Zuydam}, Natalie and Smith, {Albert V.} and Vilmundur Gudnason and Doney, {Alex S. F.} and Morris, {Andrew D.} and Leese, {Graham P.} and Palmer, {Colin N. A.} and Anand Swaroop and Taylor, {Herman A.} and Wilson, {James G.} and Alan Penman and Chen, {Ching J.} and Per-Henrik Groop and Seang-Mei Saw and Tin Aung and Klein, {Barbara E.} and Rotter, {Jerome I.} and Siscovick, {David S.} and Cotch, {Mary Frances} and Ronald Klein and Daly, {Mark J.} and Wong, {Tien Y.} and {Wellcome Trust Case Control Consor, Family Invest Nephropathy Diabet-E}",

year = "2011",

month = sep,

doi = "10.1167/iovs.11-7510",

language = "English",

volume = "52",

pages = "7593--7602",

journal = "Investigative Ophthalmology & Visual Science",

issn = "0146-0404",

publisher = "Association for Research in Vision and Ophthalmology",

number = "10",

}

Sobrin, L, Green, T, Sim, X, Jensen, RA, Tai, ES, Tay, WT, Wang, JJ, Mitchell, P, Sandholm, N, Liu, Y, Hietala, K, Iyengar, SK, Brooks, M, Buraczynska, M, Van Zuydam, N, Smith, AV, Gudnason, V, Doney, ASF, Morris, AD, Leese, GP , Palmer, CNA, Swaroop, A, Taylor, HA, Wilson, JG, Penman, A, Chen, CJ, Groop, P-H, Saw, S-M, Aung, T, Klein, BE, Rotter, JI, Siscovick, DS, Cotch, MF, Klein, R, Daly, MJ, Wong, TY & Wellcome Trust Case Control Consor, Family Invest Nephropathy Diabet-E 2011, 'Candidate Gene Association Study for Diabetic Retinopathy in Persons with Type 2 Diabetes: The Candidate Gene Association Resource (CARe)', Investigative Ophthalmology & Visual Science, vol. 52, no. 10, pp. 7593-7602. https://doi.org/10.1167/iovs.11-7510

TY - JOUR

T1 - Candidate Gene Association Study for Diabetic Retinopathy in Persons with Type 2 Diabetes

T2 - The Candidate Gene Association Resource (CARe)

AU - Sobrin, Lucia

AU - Green, Todd

AU - Sim, Xueling

AU - Jensen, Richard A.

AU - Tai, E. Shyong

AU - Tay, Wan Ting

AU - Wang, Jie Jin

AU - Mitchell, Paul

AU - Sandholm, Niina

AU - Liu, Yiyuan

AU - Hietala, Kustaa

AU - Iyengar, Sudha K.

AU - Brooks, Matthew

AU - Buraczynska, Monika

AU - Van Zuydam, Natalie

AU - Smith, Albert V.

AU - Gudnason, Vilmundur

AU - Doney, Alex S. F.

AU - Morris, Andrew D.

AU - Leese, Graham P.

AU - Palmer, Colin N. A.

AU - Swaroop, Anand

AU - Taylor, Herman A.

AU - Wilson, James G.

AU - Penman, Alan

AU - Chen, Ching J.

AU - Groop, Per-Henrik

AU - Saw, Seang-Mei

AU - Aung, Tin

AU - Klein, Barbara E.

AU - Rotter, Jerome I.

AU - Siscovick, David S.

AU - Cotch, Mary Frances

AU - Klein, Ronald

AU - Daly, Mark J.

AU - Wong, Tien Y.

AU - Wellcome Trust Case Control Consor, Family Invest Nephropathy Diabet-E

PY - 2011/9

Y1 - 2011/9

N2 - PURPOSE. To investigate whether variants in cardiovascular candidate genes, some of which have been previously associated with type 2 diabetes (T2D), diabetic retinopathy (DR), and diabetic nephropathy (DN), are associated with DR in the Candidate gene Association Resource (CARe).METHODS. Persons with T2D who were enrolled in the study (n = 2691) had fundus photography and genotyping of single nucleotide polymorphisms (SNPs) in 2000 candidate genes. Two case definitions were investigated: Early Treatment Diabetic Retinopathy Study (ETDRS) grades >= 14 and >= 30. The chi(2) analyses for each CARe cohort were combined by Cochran-Mantel- Haenszel (CMH) pooling of odds ratios (ORs) and corrected for multiple hypothesis testing. Logistic regression was performed with adjustment for other DR risk factors. Results from replication in independent cohorts were analyzed with CMH meta-analysis methods.RESULTS. Among 39 genes previously associated with DR, DN, or T2D, three SNPs in P-selectin (SELP) were associated with DR. The strongest association was to rs6128 (OR = 0.43, P = 0.0001, after Bonferroni correction). These associations remained significant after adjustment for DR risk factors. Among other genes examined, several variants were associated with DR with significant P values, including rs6856425 tagging alpha-Liduronidase (IDUA) (P = 2.1 X 10(-5), after Bonferroni correction). However, replication in independent cohorts did not reveal study-wide significant effects. The P values after replication were 0.55 and 0.10 for rs6128 and rs6856425, respectively.CONCLUSIONS. Genes associated with DN, T2D, and vascular diseases do not appear to be consistently associated with DR. A few genetic variants associated with DR, particularly those in SELP and near IDUA, should be investigated in additional DR cohorts. (Invest Ophthalmol Vis Sci. 2011;52:7593-7602) DOI:10.1167/iovs.11-7510

AB - PURPOSE. To investigate whether variants in cardiovascular candidate genes, some of which have been previously associated with type 2 diabetes (T2D), diabetic retinopathy (DR), and diabetic nephropathy (DN), are associated with DR in the Candidate gene Association Resource (CARe).METHODS. Persons with T2D who were enrolled in the study (n = 2691) had fundus photography and genotyping of single nucleotide polymorphisms (SNPs) in 2000 candidate genes. Two case definitions were investigated: Early Treatment Diabetic Retinopathy Study (ETDRS) grades >= 14 and >= 30. The chi(2) analyses for each CARe cohort were combined by Cochran-Mantel- Haenszel (CMH) pooling of odds ratios (ORs) and corrected for multiple hypothesis testing. Logistic regression was performed with adjustment for other DR risk factors. Results from replication in independent cohorts were analyzed with CMH meta-analysis methods.RESULTS. Among 39 genes previously associated with DR, DN, or T2D, three SNPs in P-selectin (SELP) were associated with DR. The strongest association was to rs6128 (OR = 0.43, P = 0.0001, after Bonferroni correction). These associations remained significant after adjustment for DR risk factors. Among other genes examined, several variants were associated with DR with significant P values, including rs6856425 tagging alpha-Liduronidase (IDUA) (P = 2.1 X 10(-5), after Bonferroni correction). However, replication in independent cohorts did not reveal study-wide significant effects. The P values after replication were 0.55 and 0.10 for rs6128 and rs6856425, respectively.CONCLUSIONS. Genes associated with DN, T2D, and vascular diseases do not appear to be consistently associated with DR. A few genetic variants associated with DR, particularly those in SELP and near IDUA, should be investigated in additional DR cohorts. (Invest Ophthalmol Vis Sci. 2011;52:7593-7602) DOI:10.1167/iovs.11-7510

KW - GENOME-WIDE ASSOCIATION

KW - CORONARY-ARTERY-DISEASE

KW - COMMON VARIANTS

KW - RISK-FACTORS

KW - ERYTHROPOIETIN GENE

KW - LINKAGE ANALYSES

KW - BLOOD-PRESSURE

KW - UNITED-STATES

KW - FTO GENE

KW - COMPLICATIONS

U2 - 10.1167/iovs.11-7510

DO - 10.1167/iovs.11-7510

M3 - Article

C2 - 21873659

SN - 0146-0404

VL - 52

SP - 7593

EP - 7602

JO - Investigative Ophthalmology & Visual Science

JF - Investigative Ophthalmology & Visual Science

IS - 10

ER -

Candidate Gene Association Study for Diabetic Retinopathy in Persons with Type 2 Diabetes: The Candidate Gene Association Resource (CARe)

Abstract

Keywords

UN SDGs

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