Elevated serum urate concentrations can cause gout, a prevalent and painful inflammatory arthritis. By combining data from >140,000 individuals of European ancestry within the Global Urate Genetics Consortium (GUGC), we identified and replicated 28 genome-wide significant loci in association with serum urate concentrations (18 new regions in or near TRIM46, INHBB, SFMBT1, TMEM171, VEGFA, BAZ1B, PRKAG2, STC1, HNF4G, A1CF, ATXN2, UBE2Q2, IGF1R, NFAT5, MAF, HLF, ACVR1B-ACVRL1 and B3GNT4). Associations for many of the loci were of similar magnitude in individuals of non-European ancestry. We further characterized these loci for associations with gout, transcript expression and the fractional excretion of urate. Network analyses implicate the inhibins-activins signaling pathways and glucose metabolism in systemic urate control. New candidate genes for serum urate concentration highlight the importance of metabolic control of urate production and excretion, which may have implications for the treatment and prevention of gout.

Chronic kidney disease (CKD), impairment of kidney function, is a serious public health problem, and the assessment of genetic factors influencing kidney function has substantial clinical relevance. Here, we report a meta-analysis of genome-wide association studies for kidney function–related traits, including 71,149 east Asian individuals from 18 studies in 11 population-, hospital- or family-based cohorts, conducted as part of the Asian Genetic Epidemiology Network (AGEN). Our meta-analysis identified 17 loci newly associated with kidney function–related traits, including the concentrations of blood urea nitrogen, uric acid and serum creatinine and estimated glomerular filtration rate based on serum creatinine levels (eGFRcrea) (P < 5.0 × 10−8). We further examined these loci with in silico replication in individuals of European ancestry from the KidneyGen, CKDGen and GUGC consortia, including a combined total of ~110,347 individuals. We identify pleiotropic associations among these loci with kidney function–related traits and risk of CKD. These findings provide new insights into the genetics of kidney function.

ObjectivesTo examine the association between plasma concentrations of antioxidative micronutrients and leukocyte telomere length (LTL) in elderly adults.DesignCross-sectional cohort study.SettingAustrian Stroke Prevention Study, a population-based cohort study on brain aging.ParticipantsIndividuals with a mean age of 66 ± 7 (n = 786; 58% female).MeasurementsConcentrations of vitamin C, lutein, zeaxanthin, β-cryptoxanthin, canthaxanthin, lycopene, α- and γ-tocopherol, α- and β-carotene, and retinol in plasma, advanced oxidation protein products as a measure of oxidative stress in serum, and LTL were measured. Vitamins and carotenoids were measured using high-performance liquid chromatography, advanced oxidation protein products using spectrophotometry, and telomere length using quantitative real-time polymerase chain reaction.ResultsMultiple linear regression analyses with adjustment for age and sex demonstrated that higher lutein, zeaxanthin, and vitamin C concentrations were strongly associated with longer telomere length. The associations were independent of body mass index, maximum oxygen uptake, and vascular risk factors and were not mediated by advanced oxidation protein products content.ConclusionThis study provides first evidence that higher lutein, zeaxanthin, and vitamin C concentrations in plasma are associated with longer LTL in normal elderly persons and suggest a protective role of these vitamins in telomere maintenance.

Background: Physical activity and cardiorespiratory fitness relate to better cognitive performance. Little is known about the effects of fitness on structural brain abnormalities in the elderly. Objective: Assess the association between maximal oxygen consumption (VO₂max), white matter lesion (WML) volume and brain parenchymal fraction (BPF) in a large cohort of community-dwelling elderly individuals. Methods: The study population consisted of 715 participants of the Austrian Stroke Prevention Study who underwent brain MRI with semi-automated measurement of WML volume (cm³) and automated assessment of BPF (%) by the use of SIENAX. A maximal exercise stress test was done on a bicycle ergometer. VO₂max was calculated based on maximum and resting heart rate. Results: After adjustment for possible confounders, VO₂max was independently associated with WML volume (β = –0.10; p = 0.02); no significant relationship existed with silent cerebral infarcts and BPF. Associations between VO₂max and WML load were only significant in men, but not in women. Conclusion: Our findings may have important preventive implications because WMLs are known to be a major determinant of cognitive decline and disability in old age.

Background and Purpose Ischemic stroke (IS) shares many common risk factors with coronary artery disease (CAD). We hypothesized that genetic variants associated with myocardial infarction (MI) or CAD may be similarly involved in the etiology of IS. To test this hypothesis, we evaluated whether single-nucleotide polymorphisms (SNPs) at 11 different loci recently associated with MI or CAD through genome-wide association studies were associated with IS. Methods Meta-analyses of the associations between the 11 MI-associated SNPs and IS were performed using 6865 cases and 11 395 control subjects recruited from 9 studies. SNPs were either genotyped directly or imputed; in a few cases a surrogate SNP in high linkage disequilibrium was chosen. Logistic regression was performed within each study to obtain study-specific βs and standard errors. Meta-analysis was conducted using an inverse variance weighted approach assuming a random effect model. Results Despite having power to detect odds ratio of 1.09–1.14 for overall IS and 1.20–1.32 for major stroke subtypes, none of the SNPs were significantly associated with overall IS and/or stroke subtypes after adjusting for multiple comparisons. Conclusions Our results suggest that the major common loci associated with MI risk do not have effects of similar magnitude on overall IS but do not preclude moderate associations restricted to specific IS subtypes. Disparate mechanisms may be critical in the development of acute ischemic coronary and cerebrovascular events.