methylglyoxal-bis(butylamidinohydrazone) and Diabetes-Mellitus--Type-2

Quantify the impact of genetic and socioeconomic factors on risk of type 2 diabetes (T2D) and obesity.. Among participants in the Mass General Brigham Biobank (MGBB) and UK Biobank (UKB), we used logistic regression models to calculate cross-sectional odds of T2D and obesity using 1) polygenic risk scores for T2D and BMI and 2) area-level socioeconomic risk (educational attainment) measures. The primary analysis included 26,737 participants of European genetic ancestry in MGBB with replication in UKB (N = 223,843), as well as in participants of non-European ancestry (MGBB N = 3,468; UKB N = 7,459).. The area-level socioeconomic measure most strongly associated with both T2D and obesity was percent without a college degree, and associations with disease prevalence were independent of genetic risk (P < 0.001 for each). Moving from lowest to highest quintiles of combined genetic and socioeconomic burden more than tripled T2D (3.1% to 22.2%) and obesity (20.9% to 69.0%) prevalence. Favorable socioeconomic risk was associated with lower disease prevalence, even in those with highest genetic risk (T2D 13.0% vs. 22.2%, obesity 53.6% vs. 69.0% in lowest vs. highest socioeconomic risk quintiles). Additive effects of genetic and socioeconomic factors accounted for 13.2% and 16.7% of T2D and obesity prevalence, respectively, explained by these models. Findings were replicated in independent European and non-European ancestral populations.. Genetic and socioeconomic factors significantly interact to increase risk of T2D and obesity. Favorable area-level socioeconomic status was associated with an almost 50% lower T2D prevalence in those with high genetic risk.

Topics: Cross-Sectional Studies; Diabetes Mellitus, Type 2; Genetic Predisposition to Disease; Humans; Obesity; Prevalence; Risk Factors; Socioeconomic Factors

We aimed to discover loci associated with triglyceride (TG) levels in the context of type 2 diabetes (T2D). We conducted a genome-wide association study (GWAS) in 424,120 genotyped participants of the UK Biobank (UKB) with T2D status and TG levels.. We stratified the cohort based on T2D status and conducted association analyses of TG levels for genetic variants with minor allele count (MAC) at least 20 in each stratum. Effect differences of genetic variants by T2D status were determined by Cochran's Q-test and we validated the significantly associated variants in the Mass General Brigham Biobank (MGBB).. Among 21,176 T2D and 402,944 non-T2D samples from UKB, stratified GWAS identified 19 and 315 genomic risk loci significantly associated with TG levels, respectively. Only chr6p21.32 exhibited genome-wide significant heterogeneity (I2 = 98.4%; pheterogeneity = 2.1x10-15), with log(TG) effect estimates of -0.066 (95%CI: -0.082, -0.050) and 0.002 (95%CI: -0.002, 0.006) for T2D and non-T2D, respectively. The lead variant rs9274619:A (allele frequency 0.095) is located 2Kb upstream of the HLA-DQB1 gene, between HLA-DQB1 and HLA-DQA2 genes. We replicated this finding among 25,137 participants (6,951 T2D cases) of MGBB (pheterogeneity = 9.5x10-3). Phenome-wide interaction association analyses showed that the lead variant was strongly associated with a concomitant diagnosis of type 1 diabetes (T1D) as well as diabetes-associated complications.. In conclusion, we identified an intergenic variant near HLA-DQB1/DQA2 significantly associates with decreased triglycerides only among those with T2D and highlights an immune overlap with T1D.

Topics: Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Genome-Wide Association Study; Humans; Polymorphism, Single Nucleotide; Triglycerides