Assessment of genetic risk of type 2 diabetes among Pakistanis based on GWAS-implicated loci

Sabiha, Bibi; Bhatti, Attya; Fan, Kang-Hsien; John, Peter; Aslam, Muhammad; Ali, Johar; Feingold, Eleanor; Demirci, Fuat; Kamboh, M. Ilyas

doi:10.1016/j.gene.2021.145563

Cited by 10 publications

(8 citation statements)

References 63 publications

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“…GLIS3 / rs7041847 was previously marked as a risk factor for T2DM in the Chinese population. 69 Similar to our finding, one recent study 36 also replicated variant GLIS3 / rs7041847 in the Pakistani population.…”

Section: Discussionsupporting

confidence: 90%

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Validation of Genome-Wide Association Studies (GWAS)-Identified Type 2 Diabetes Mellitus Risk Variants in Pakistani Pashtun Population

Jan¹,

Zakiullah²,

Khuda³

et al. 2023

JAFES

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Objective Recent GWAS largely conducted in European populations have successfully identified multiple genetic risk variants associated with Type 2 Diabetes Mellitus (T2DM). However, the effects conferred by these variants in the Pakistani population have not yet been fully elucidated. The objective of this study was to examine European GWAS-identified T2DM risk variants in the Pakistani Pashtun population to better understand the shared genetic basis of T2DM in the European and Pakistani cohorts. Methodology A total of 100 T2DM patients and 100 healthy volunteers of Pashtun ethnicity were enrolled in this study. Both groups were genotyped for 8 selected single nucleotide polymorphisms (SNPs) using the Sequenom MassARRAY ® platform. The association between selected SNPs and T2DM was determined by using appropriate statistical tests. Results Of the 8 studied SNPs, 5 SNPs, SLC30A8 / rs13266634 ( p =0.031, OR=2.13), IGF2BP2 / rs4402960 ( p =0.001, OR=3.01), KCNJ11 / rs5219 ( p =0.042, OR=1.78), PPARG / rs1801282 ( p =0.042, OR=2.81) and TCF7L2 / rs7903146 ( p =0.00006, 3.41) had a significant association with T2DM. SNP GLIS3 / rs7041847 ( p =0.051, OR=2.01) showed no sufficient evidence of association. SNPs KCNQ1 / rs2237892 ( p =0.140, OR=1.61) and HHEX/IDE / s1111875 ( p =0.112, OR=1.31) showed opposite allelic effects and were not validated for T2DM risk in the study population. Among the studied SNPs, TCF7L2 / rs7903146 showed the most significant association. Conclusion Our study finding indicates that selected genome-wide significant T2DM risk variants previously identified in European descent also increase the risk of developing T2DM in the Pakistani Pashtun population.

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Section: Discussionsupporting

confidence: 90%

“…TCF7L2 / rs7903146 apart from our study was reported as a significant risk factor for T2DM by two previous replication studies in the Pakistani sub-population. 34 - 36 …”

Section: Resultsmentioning

confidence: 99%

Validation of Genome-Wide Association Studies (GWAS)-Identified Type 2 Diabetes Mellitus Risk Variants in Pakistani Pashtun Population

Jan¹,

Zakiullah²,

Khuda³

et al. 2023

JAFES

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“…We have found an association with GDM in the Hispanic ethnic stratum. UBE2E2 (rs1496653) node is an ubiquitin-conjugating enzyme associated with diabetes in some reports ( 20 , 21 , 25 ), and with GDM in other studies ( 27 , 35 , 36 ). In our work, it shows interaction with IGF2BP2, but it barely reaches significance in the Hispanic ethnicity.…”

Section: Discussionmentioning

confidence: 98%

“…Most of the nodes in Figure 2 have the name of a locus/gene that are well referenced in the literature because several SNPs with a significant association with diabetes and GDM are located nearby. Specifically, the nodes located in the central core of the graph, MNTR1B (rs1387153, rs10830962, rs10830963), IGF2BP2 (rs4402960, rs7651090), KCNJ11 (rs5215), GCKR (rs780094), CDKAL1 (rs9368222), IRS1 (rs2943634), ADRA2A (rs10885122), CRY2(rs11605924), DKGB (rs2191349), G6PC2 (rs563694), GLIS3 (rs7041847, rs7034200, rs10814916), GIPR (rs2302593), WFS1 (rs4458523), ZBED3 (rs7708285), PROX1 (rs340874), FOXA2 (rs6048205), PDX1 (rs2293941), PCSK1 (rs6235), have been referred in various GWAS as associated to diabetes ( 6 , 19 – 25 ), GDM ( 26 – 34 ) or both ( 35 , 36 ).…”

Section: Discussionmentioning

confidence: 99%

Genetic variants for prediction of gestational diabetes mellitus and modulation of susceptibility by a nutritional intervention based on a Mediterranean diet

et al. 2022

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HypothesisGestational diabetes mellitus (GDM) entails a complex underlying pathogenesis, with a specific genetic background and the effect of environmental factors. This study examines the link between a set of single nucleotide polymorphisms (SNPs) associated with diabetes and the development of GDM in pregnant women with different ethnicities, and evaluates its potential modulation with a clinical intervention based on a Mediterranean diet.Methods2418 women from our hospital-based cohort of pregnant women screened for GDM from January 2015 to November 2017 (the San Carlos Cohort, randomized controlled trial for the prevention of GDM ISRCTN84389045 and real-world study ISRCTN13389832) were assessed for evaluation. Diagnosis of GDM was made according to the International Association of Diabetes and Pregnancy Study Groups (IADPSG) criteria. Genotyping was performed by IPLEX MassARRAY PCR using the Agena platform (Agena Bioscience, SanDiego, CA). 110 SNPs were selected for analysis based on selected literature references. Statistical analyses regarding patients’ characteristics were performed in SPSS (Chicago, IL, USA) version 24.0. Genetic association tests were performed using PLINK v.1.9 and 2.0 software. Bioinformatics analysis, with mapping of SNPs was performed using STRING, version 11.5.ResultsQuality controls retrieved a total 98 SNPs and 1573 samples, 272 (17.3%) with GDM and 1301 (82.7%) without GDM. 1104 (70.2%) were Caucasian (CAU) and 469 (29.8%) Hispanic (HIS). 415 (26.4%) were from the control group (CG), 418 (26.6%) from the nutritional intervention group (IG) and 740 (47.0%) from the real-world group (RW). 40 SNPs (40.8%) presented some kind of significant association with GDM in at least one of the genetic tests considered. The nutritional intervention presented a significant association with GDM, regardless of the variant considered. In CAU, variants rs4402960, rs7651090, IGF2BP2; rs1387153, rs10830963, MTNR1B; rs17676067, GLP2R; rs1371614, DPYSL5; rs5215, KCNJ1; and rs2293941, PDX1 were significantly associated with an increased risk of GDM, whilst rs780094, GCKR; rs7607980, COBLL1; rs3746750, SLC17A9; rs6048205, FOXA2; rs7041847, rs7034200, rs10814916, GLIS3; rs3783347, WARS; and rs1805087, MTR, were significantly associated with a decreased risk of GDM, In HIS, variants significantly associated with increased risk of GDM were rs9368222, CDKAL1; rs2302593, GIPR; rs10885122, ADRA2A; rs1387153, MTNR1B; rs737288, BACE2; rs1371614, DPYSL5; and rs2293941, PDX1, whilst rs340874, PROX1; rs2943634, IRS1; rs7041847, GLIS3; rs780094, GCKR; rs563694, G6PC2; and rs11605924, CRY2 were significantly associated with decreased risk for GDM.ConclusionsWe identify a core set of SNPs in their association with diabetes and GDM in a large cohort of patients from two main ethnicities from a single center. Identification of these genetic variants, even in the setting of a nutritional intervention, deems useful to design preventive and therapeutic strategies.

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“…14 A recent study on T2DM Pakistani patients identified that 16 SNPs were in equated prevalence among our population in comparison to SNPs identified in T2DM patients from European ancestry. 15 This trend highlights for Pakistani molecular sciences community to acknowledge the importance of developing race-specified GRS in general, T2DM, and obesity in specific. However, these efforts seem insufficient and more data is needed for specific diseases, especially T2DM.…”

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confidence: 99%

Need of Countrywide Genetic Risk Scores (GRS) or Polygenic Scores (PGS) for Type-2 Diabetes Mellitus

Khan

2023

J Coll Physicians Surg Pak

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The recent surge in the cases of type-2 diabetes mellitus (T2DM) needs to be intervened with short and long-term guards and much needful preemptive explorative efforts. Unfortunately, the existing efforts still fall short. As per WHO data, Pakistan has climbed up the world diabetes ranking with a prevalence close to 15%. The factual position may be even worse due to the lack of undiagnosed cases in the poverty-stricken country with limited resources.1,2 This will burden not just diabetes therapeutics, but additional workload in ophthalmology for retinopathy, cardiac centres for atherosclerotic cardiovascular diseases, neurology for neuropathies and nephrology for early-onset chronic kidney diseases. While resource bound in every possible way, human productivity will be at a loss and money will be wasted if preventive strategies will not be evolved and implemented with full-thrust. Though primary preventions stand as the key intervention, still lessons can be learnt from the various evolving concepts by doing risk profiling especially the genetic risk scores (GRS) which can highlight the prevailing genetic predispositions among our much-varied racial population. 3

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Assessment of genetic risk of type 2 diabetes among Pakistanis based on GWAS-implicated loci

Cited by 10 publications

References 63 publications

Validation of Genome-Wide Association Studies (GWAS)-Identified Type 2 Diabetes Mellitus Risk Variants in Pakistani Pashtun Population

Validation of Genome-Wide Association Studies (GWAS)-Identified Type 2 Diabetes Mellitus Risk Variants in Pakistani Pashtun Population

Genetic variants for prediction of gestational diabetes mellitus and modulation of susceptibility by a nutritional intervention based on a Mediterranean diet

Need of Countrywide Genetic Risk Scores (GRS) or Polygenic Scores (PGS) for Type-2 Diabetes Mellitus

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