Review
Copyright ©The Author(s) 2015.
World J Diabetes. Jun 10, 2015; 6(5): 715-725
Published online Jun 10, 2015. doi: 10.4239/wjd.v6.i5.715
Table 1 Genome-wide linkage studies for diabetic nephropathy and retinopathy
Ethnicity and sample sizeType of diabetesPhenotype definitionLinkage region (LOD score or P-value or MLS)Ref.
Diabetic nephropathy
954 African American, 781 American Indians, 614 European American, 1611 Mexican Americans (FIND)1 + 2Estimated GFR10p12.311 (LOD: 2.16), 1q431 (2.26), 2q31.3 (1.91), 3p12.1 (2.19), 7q11.22 (2.19), 10p141 (2.16), 15q12 (2.84), 20q11.111 (3.34)[13]
218 African American, 335 American Indians, 119 European American, 469 Mexican Americans (FIND)1 + 2Urine ACR7q21.3 (P = 8.6 x 10-5), 10p15.31 (1.29 x 10-5), 14q23.1 (7.8 x 10-4), 18q22.31 (2.17 x 10-3)[14]
3972 Americans (African American, American Indians, European American, Mexican Americans) (FIND)1 + 2DN defined by macroalbuminuria or ESRD, ACRDN: 1q431 (LOD: 2.00), 6p24.3 (2.84), 7p21.3 (2.81), 10p15.11 (2.10), 11p15.3 (2.28), 15q21.1 (2.04)ACR: 2q22.3 (2.04), 3p13 (2.76), 7q21.2 (2.96), 16q13 (2.31), 22q12.31 (2.29)[23]
882 American (African American, American Indians, European American, Mexican Americans) (FIND)1 + 2eGFR1q431 (LOD: 1.87), 7q36.1 (4.23), 8q13.3 (2.75), 15q22.3 (2.08), 18q23.3 (1.40)[24]
100 United States sibling pairs (Joslin Study on Genetics of Diabetic Nephropathy)1Proteinuria or ESRD1q441 (MLS: 1.6), 2q14.1 (2.1), 3p13 (0.6), 5q14.2 (2.7), 10q26.1 (2.4), 17p13.1 (1.9), 19q13.431 (3.1), 20p12.1 (1.8)[15]
63 extended United States families (Joslin Study on Genetics of Diabetic Nephropathy)2GFR2q33.3 (LOD: 4.1), 10q23.31 (3.1), 18p11.22 (2.2)[19]
556 Finnish, Danish, and French (FinnDiane)1Macroalbuminuria or ESRD3q21-251 (LOD: 0.76), 6p21 (2.31), 9p21.2, 16p12, 19q131 (1.61), 22q11 (2.78)[16]
83 Finnish sibling pairs1Macroalbuminuria or ESRD3q21.3-231 (MLS: 2.67)[21]
18 Turkish family + 101 sibling pairs of Pima India2Macroalbuminuria18q22.3-231 (max LOD:6.14)[17]
201 Pima India sibling pairs2Macroalbuminuria or ESRD3q26.11 (LOD: 1.48), 7q32.3 (2.04), 20p12.3 (1.83)[18]
206 African American sibling pairs2ESRD3q13.31 (LOD: 4.55), 7p21.1 (3.59), 18q22.11 (3.72)[22]
691 West African2GFR7p12.2 (LOD: 1.84), 16q24.1 (3.56), 17p13.2 (2.08)[20]
Diabetic retinopathy
282 Mexican American sibling pairs2Non-proliferative DR and proliferative DR3q12.3 (LOD: 2.41), 12p13.31 (2.47), 20q13.12 (4.47), 6p24.1 (2.28), 15q26.3 (2.53), 19q13.42 (2.21)[45]
725 Pima Indian sibling pairs2Worse eye score1p36.13 (LOD: 3.1)[46]
210 Pima Indian sibling pairs2Hemorrhage, microaneurysm, and proliferative DR3q26.31 (LOD: 1.36), 9q22.33 (1.46)[18]
Table 2 Genome-wide association studies for diabetic nephropathy, retinopathy, and neuropathy
PatientsEthnicCaseControlGeneRef.Replication studiesNon-replication studies
Diabetic nephropathy
T2DMJapanese459 DN242ELMO11[25]26, 27, 28, 29, 3031, 32
T2DMEuropean105 ESRD102PVT1[33]
T2DMAfrican American965 ESRD1029SASH1, RPS12,AUH, MSRB3, LIMK2-SKI1, APOL3-MYH91[34]35
T1DMCaucasian (GoKinD, DCCT/EDIC)820 ESRD885FRMD31, CARS, CPVL/CHN2, 13q3 between MYO16/IRS21[39]40, 41, 4242, 30
T1DMCaucasian547 ESRD549ZMIZ1[29]
T1DMGENIE (UK-ROI, FinnDiane, GoKinUS) + 9 follow-up studiesStage 1: 4315 ESRDStage 2: 1880 ESRDStage 1: 8568Stage 2: 6656AFF3, RGMA/MCTP2, ERBB4[43]
T1DMCaucasian(FinnDiane + 7 follow-up studies)5675 T1DMUrine albumin excretion ratePSD3, SH2D4A[44]
Diabetic retinopathy
T1DMCaucasian (GoKinD and EDIC)2829 PDR and macular edema1856AKT3/ZNF238, LEKR1/CCNL1, KRT18P34/VEPH1, A2BP1[47]
T2DMTaiwanese174 NPDR and PDR575MYSM1, FSTL5, C5orfF21, PLXD2, ARHGAP22, HS6ST3[48]
T2DMTaiwanese437 PDR570TBC1D4-COMMD6-UCHL3, LRP2-BBS5, and ARL4C-SH3BP4[49]
T2DMMexican-American103 severe DR183CAMK4, FMN1 genes[50]
Diabetic neuropathy
United KingdomUnited Kingdom (GoDART)572 diabetic neuropathic pain2491GFRA2[51]