COMPLICATIONS diabetes (DoD) and poor glycemic control (2). Genetic factors are also implicated, with heritability of 52% for proliferative DR (PDR) (3,4). Several candidate gene and genome-wide association studies (GWAS) have been conducted (5-11). Although several polymorphisms have been suggested to be associated with DR, few have been convincingly replicated (10,12-15). There are several reasons why studies have not yielded consistent findings. The genetic effects are likely modest, and identification requires large sample sizes. Previous studies have not consistently accounted for the strongest two covariates, DoD and glycemic control. Liability threshold (LT) modeling is one way to incorporate these covariates while also increasing statistical power (16). Finally,

BackgroundThe highest prevalence of migraine is detected among people who are of working age. The aim of this study was to assess the burden of migraine in an occupational health care setting using real world data collected as a part of routine clinical practice.MethodsThis retrospective register study included migraineurs using occupational health care at the private health care provider Terveystalo. An age and gender matched control population was established for comparison. Electronic medical records were assessed for overall and migraine related health care visits, sick-leaves and comorbidities. Stratification to acute and prophylactic treatment groups along with prophylactic treatment lines was based on prescriptions.ResultsAmong the 369,383 individuals in the study cohort, 7.4% women and 2.1% men were identified having a diagnosis of migraine. Prophylactic medication was prescribed to 13% of migraine patients and exclusively acute medication to 37%. Although migraine related visits and sick-leave days were significantly lower than overall visits or sick-leave days, both increased by prophylactic treatment line. The number of visits rose from 13.8 to 26.2 and sick-leave days from 16.8 to 30.4 per patient-year, in those without prophylaxis vs. ≥3 prophylactic treatments. Moreover, migraine patients had 1.7-fold increase in visits and 1.8-fold increase in sick leave days on average per patient-year, when compared to the control population. Depression and anxiety were 1.8-fold more common among patients with migraine, and the frequency also increase by treatment line.ConclusionsMigraine burden increased by each failed treatment line and was associated with increased comorbidity. In addition, migraine patients had significantly higher extent of visits and sick-leave days as well as extent of comorbidities when compared to their age- and gender-matched counterparts.

Background The genetic determinants of diabetic nephropathy remain poorly understood. We aimed to identify novel susceptibility genes for diabetic nephropathy. Patients and methods We performed a genome-wide association study using 1000 Genomes-based imputation in type 1 diabetic patients comparing diabetic nephropathy cases with proteinuria with or without renal failure to controls with diabetes for more than 15 years and no evidence of renal disease. Results None of the SNPs tested in a discovery cohort composed of 683 cases and 779 controls reached genome-wide statistical significance. The 46 top hits (p-value < 10−5) were then sought for first-stage analysis in US-GoKinD an independent population of 820 cases and 885 controls. Two SNPs, in strong linkage disequilibrium with each other, located in the SORBS1 gene, were consistently and significantly (p < 10−4) associated with diabetic nephropathy. The minor rs1326934-C allele was less frequent in cases than in controls (0.34 vs 0.43) and was associated with a decreased risk for diabetic nephropathy: OR = 0.70 [0.60 – 0.82]. However, this association was not observed in a second-stage with two additional diabetic nephropathy cohorts UK-ROI (p=0.15) and FINNDIANE (p = 0.44) totaling 2,142 cases and 2,494 controls. Altogether, the random-effect meta-analyzed rs1326934-C allele OR for diabetic nephropathy was 0.83 [0.72 – 0.96] (p = 0.009). Conclusion These data suggest that SORBS1 might be a gene involved in diabetic nephropathy.

Purpose Diabetic retinopathy is the most common eye complication in patients with diabetes. The purpose of this study is to identify genetic factors contributing to severe diabetic retinopathy. Methods A genome-wide association approach was applied. In the Genetics of Diabetes Audit and Research in Tayside Scotland (GoDARTS) datasets, cases of severe diabetic retinopathy were defined as type 2 diabetic patients who were ever graded as having severe background retinopathy (Level R3) or proliferative retinopathy (Level R4) in at least one eye according to the Scottish Diabetic Retinopathy Grading Scheme or who were once treated by laser photocoagulation. Controls were diabetic individuals whose longitudinal retinopathy screening records were either normal (Level R0) or only with mild background retinopathy (Level R1) in both eyes. Significant SNPs were taken forward for meta-analysis using multiple Caucasian cohorts. Results 560 cases of type 2 diabetes with severe diabetic retinopathy and 4,106 controls were identified in the GoDARTS cohort. We revealed that rs3913535 in the NADPH Oxidase 4 (NOX4) gene reached a P value of 4.05 × 10-9. Two nearby SNPs, rs10765219 and rs11018670 also showed promising P values (P values = 7.41 × 10-8 and 1.23 × 10-8, respectively). In the meta-analysis using multiple Caucasian cohorts (excluding GoDARTS), rs10765219 and rs11018670 showed associations for diabetic retinopathy (P=0.003 and 0.007, respectively) while the P value of rs3913535 was not significant (P=0.429). Conclusion This genome-wide association study of severe diabetic retinopathy suggests new evidence for the involvement of the NOX4 gene.