Dataset Information

Novel susceptibility loci identified in a genome-wide association study of type 2 diabetes complications in population of Latvia.

ABSTRACT:

Background

Type 2 diabetes complications cause a serious emotional and economical burden to patients and healthcare systems globally. Management of both acute and chronic complications of diabetes, which dramatically impair the quality of patients' life, is still an unsolved issue in diabetes care, suggesting a need for early identification of individuals with high risk for developing diabetes complications.

Methods

We performed a genome-wide association study in 601 type 2 diabetes patients after stratifying them according to the presence or absence of four types of diabetes complications: diabetic neuropathy, diabetic nephropathy, macrovascular complications, and ophthalmic complications.

Results

The analysis revealed ten novel associations showing genome-wide significance, including rs1132787 (GYPA, OR?=?2.71; 95% CI?=?2.02-3.64) and diabetic neuropathy, rs2477088 (PDE4DIP, OR?=?2.50; 95% CI?=?1.87-3.34), rs4852954 (NAT8, OR?=?2.27; 95% CI?=?2.71-3.01), rs6032 (F5, OR?=?2.12; 95% CI?=?1.63-2.77), rs6935464 (RPS6KA2, OR?=?2.25; 95% CI?=?6.69-3.01) and macrovascular complications, rs3095447 (CCDC146, OR?=?2.18; 95% CI?=?1.66-2.87) and ophthalmic complications. By applying the targeted approach of previously reported susceptibility loci we managed to replicate three associations: MAPK14 (rs3761980, rs80028505) and diabetic neuropathy, APOL1 (rs136161) and diabetic nephropathy.

Conclusions

Together these results provide further evidence for the implication of genetic factors in the development of type 2 diabetes complications and highlight several potential key loci, able to modify the risk of developing these conditions. Moreover, the candidate variant approach proves a strong and consistent effect for multiple variants across different populations.

SUBMITTER: Ustinova M

PROVIDER: S-EPMC7802349 | biostudies-literature | 2021 Jan

REPOSITORIES: biostudies-literature

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Publications

Novel susceptibility loci identified in a genome-wide association study of type 2 diabetes complications in population of Latvia.

Ustinova Monta M Peculis Raitis R Rescenko Raimonds R Rovite Vita V Zaharenko Linda L Elbere Ilze I Silamikele Laila L Konrade Ilze I Sokolovska Jelizaveta J Pirags Valdis V Klovins Janis J

BMC medical genomics 20210111 1

<h4>Background</h4>Type 2 diabetes complications cause a serious emotional and economical burden to patients and healthcare systems globally. Management of both acute and chronic complications of diabetes, which dramatically impair the quality of patients' life, is still an unsolved issue in diabetes care, suggesting a need for early identification of individuals with high risk for developing diabetes complications.<h4>Methods</h4>We performed a genome-wide association study in 601 type 2 diabet ...[more]

PMID: 33430853

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Project description:Metabolic syndrome (MetS) is prevalent in type 2 diabetes (T2D) patients. The comorbidity of MetS and T2D increases the risk of cardiovascular complications. The aim of the present study was to determine the T2D-related genetic variants that contribute to MetS-related components in T2D patients of Chinese ancestry. We successfully genotyped 25 genome wide association study validated T2D-related single nucleotide polymorphisms (SNPs) among 5,169 T2D individuals and 4,560 normal glycemic controls recruited from the Chinese National Diabetes and Metabolic Disorders Study (DMS). We defined MetS in this population using the harmonized criteria (2009) combined with the Chinese criteria for abdominal obesity. The associations between SNPs and MetS-related components, as well as the associations between SNPs and risk for T2D with or without MetS, were subjected to logistic regression analysis adjusted for age and sex. Results showed that the T2D risk alleles of rs243021 located near BCL11A, rs10830963 in MTNR1B, and rs2237895 in KCNQ1 were related to a lower risk for abdominal obesity in T2D patients (rs243021: 0.92 (0.84, 1.00), P = 4.42 × 10-2; rs10830963: 0.92 (0.85, 1.00), P = 4.07 × 10-2; rs2237895: 0.89 (0.82, 0.98), P = 1.29 × 10-2). The T2D risk alleles of rs972283 near KLF14 contributed to a higher risk of elevated blood pressure (1.10 (1.00, 1.22), P = 4.48 × 10-2), while the T2D risk allele of rs7903146 in TCF7L2 was related to a lower risk for elevated blood pressure (0.74 (0.61, 0.90), P = 2.56 × 10-3). The T2D risk alleles of rs972283 near KLF14 and rs11634397 near ZFAND6 were associated with a higher risk for elevated triglycerides (rs972283: 1.11 (1.02, 1.24), P = 1.46 × 10-2; rs11634397: 1.14 (1.00, 1.29), P = 4.66 × 10-2), while the T2D risk alleles of rs780094 in GCKR and rs7903146 in TCF7L2 were related to a lower risk of elevated triglycerides (rs780094: 0.86 (0.80, 0.93), P = 1.35 × 10-4; rs7903146: 0.82 (0.69, 0.98), P = 3.18 × 10-2). The genotype risk score of the 25 T2D-related SNPs was related to a lower risk for abdominal obesity (Ptrend = 1.29 × 10-2) and lower waist circumference (P = 2.20 × 10-3). Genetic variants of WFS1, CDKAL1, CDKN2BAS, TCF7L2, HHEX, KCNQ1, TSPAN8/LGR5, FTO, and TCF2 were associated with the risk for T2D with MetS, as well as the risk for development of T2D with at least one of the MetS components (P < 0.05). In addition, genetic variants of BCL11A, GCKR, ADAMTS9, CDKAL1, KLF14, CDKN2BAS, TCF7L2, CDC123/CAMK1D, HHEX, MTNR1B, and KCNQ1 contributed to the risk for T2D without MetS (P < 0.05). In conclusion, these findings highlight the contribution of T2D-related genetic loci to MetS in a Chinese Han population. The study also provides insight into the pleotropic effects of genome-wide association loci of diabetes on metabolic regulation.

Dataset Information

Novel susceptibility loci identified in a genome-wide association study of type 2 diabetes complications in population of Latvia.

Background

Methods

Results

Conclusions

Publications

Novel susceptibility loci identified in a genome-wide association study of type 2 diabetes complications in population of Latvia.

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