Common and Distinct Genetic Architecture of Age at Diagnosis of Diabetes in South Indian and European Populations.

OBJECTIVE: South Asians are diagnosed with type 2 diabetes (T2D) more than a decade earlier in life than seen in European populations. We hypothesized that studying the genomics of age of diagnosis in these populations may give insight into the earlier age diagnosis of T2D among individuals of South Asian descent. RESEARCH DESIGN AND METHODS: We conducted a meta-analysis of genome-wide association studies (GWAS) of age at diagnosis of T2D in 34,001 individuals from four independent cohorts of European and South Asian Indians. RESULTS: We identified two signals near the TCF7L2 and CDKAL1 genes associated with age at the onset of T2D. The strongest genome-wide significant variants at chromosome 10q25.3 in TCF7L2 (rs7903146; P = 2.4 × 10-12, ß = -0.436; SE 0.02) and chromosome 6p22.3 in CDKAL1 (rs9368219; P = 2.29 × 10-8; ß = -0.053; SE 0.01) were directionally consistent across ethnic groups and present at similar frequencies; however, both loci harbored additional independent signals that were only present in the South Indian cohorts. A genome-wide signal was also obtained at chromosome 10q26.12 in WDR11 (rs3011366; P = 3.255 × 10-8; ß = 1.44; SE 0.25), specifically in the South Indian cohorts. Heritability estimates for the age at diagnosis were much stronger in South Indians than Europeans, and a polygenic risk score constructed based on South Indian GWAS explained ∼2% trait variance. CONCLUSIONS: Our findings provide a better understanding of ethnic differences in the age at diagnosis and indicate the potential importance of ethnic differences in the genetic architecture underpinning T2D.

Humidity Sustainable Hydrophobic Poly(vinylidene fluoride)-Carbon Nanotubes Foam Based Piezoelectric Nanogenerator.

Light weight lead free, polymer, and carbon nanotubes based flexible piezoelectric nanogenerators have prompted widespread concern for harvesting mechanical energy and powering next generation electronics devices. Herein, lightweight polyvinylidene fluoride (PVDF)-carbon nanotube (CNT) foam was prepared to fabricate humid resistant hydrophobic flexible piezoelectric nanogenerator to converts mechanical energy into electricity for the first time. Hydrophobic piezoelectric PVDF-CNT foam with density of 0.15 g/cm3 was prepared by solution route. PVDF-CNT foam exhibited crystalline and a well-defined chain likes structure with 65% fraction of ß-phase. Self-poled PVDF-CNT foam shows piezoelectric charge coefficient (d33) of 9.4 pC/N. High d33 of PVDF-CNT foam is caused by dipole alignment induced by local electric field of CNT in the microcellular structure of PVDF. The developed foam exhibits ultrahigh dielectric constant (ε') ∼ 3048 at 150 Hz. Flexible piezoelectric PVDF-CNT foam based nanogenerator was fabricated, which generates high output voltage ∼12 V and current density of 30 nA/cm2 at small compressive pressure of 0.02 kgf. Piezoelectric output performance was measured under different humid condition and an output voltage up to 8 V was achieved even under 60% RH condition. PVDF-CNT foam exhibited hydrophobic behavior and high surface water contact angle of 139°. Such high output voltage even under small pressure, without applying electrical poling and under humid condition was originated though CNT induced self-alignment of electric dipoles in PVDF polymer. These excellent performances of developed foam based device confirmed its potential application in organic based ultrasensitive self-powered nanosensors and nanosystems.

Association of rs11643718 SLC12A3 and rs741301 ELMO1 Variants with Diabetic Nephropathy in South Indian Population.

This study reports on the association of genetic variants selected from previous genome-wide association studies for type 2 diabetic nephropathy in south Indians. Eight variants were genotyped in 601 type 2 diabetic subjects without nephropathy (DM) and 583 type 2 diabetic subjects with nephropathy (DN) by MassARRAY. The minor allele frequencies of rs11643718 SLC12A3 variant and rs741301 ELMO1 variant were significantly different between DM and DN groups (P = 0.029 and 0.016, respectively). A combined analysis showed that the subjects carrying the risk genotypes of both these variants (GG of rs11643718 + AG/AA of rs741301) had a significant association with DN with an odds ratio [adjusted for age, sex, Body Mass Index (BMI), HbA1c, and systolic Blood Pressure (BP)] of 1.73 (1.30-2.30, P = 1.72 × 10-4 ) as compared to subjects carrying all other genotype combinations. This is the first study to report a significant association of the SLC12A3 rs11643718 and ELMO1 rs741301 (Single nucleotide Polymorphism) SNPs with diabetic nephropathy in south Indians.