Value of reduced glomerular filtration rate assessment with cardiometabolic index: insights from a population-based Chinese cohort

Abstract Background Recent studies have suggested that cardiometabolic index (CMI), a novel estimate of visceral adipose tissue, could be of use in the evaluation of cardiovascular risk factors. However, the potential utility and clinical significance of CMI in the detection of reduced estimated glomerular filtration rate (eGFR) remains uncertain. The purpose of this study was to investigate the usefulness of CMI in assessing reduced eGFR in the general Chinese population. Methods This cross-sectional analysis included 11,578 participants (mean age: 53.8 years, 53.7% females) from Northeast China Rural Cardiovascular Health Study (NCRCHS) of general Chinese population (data collected from January 2013 to August 2013). CMI was calculated by triglyceride to high density lipoprotein cholesterol ratio multiply waist-to-height ratio. Reduced eGFR was defined as eGFR< 60 ml/min per 1.73m2. Multivariate regressions were performed to determine CMI’s association with eGFR value and eGFR reduction, ROC analyses were employed to investigate CMI’s discriminating ability for decreased eGFR. Results The prevalence of reduced eGFR was 1.7% in males and 2.5% in females. CMI was notably more adverse in reduced eGFR groups, regardless of genders. In fully adjusted multivariate linear models, each 1 SD increment of CMI caused 3.150 ml/min per 1.73m2 and 2.411 ml/min per 1.73m2 loss of eGFR before CMI reached 1.210 and 1.520 in males and females, respectively. In logistic regression analyses, per 1 SD increase of CMI brought 51.6% additional risk of reduced eGFR in males while caused 1.347 times of risk in females. After divided into quartiles, people in the top quartile of CMI had higher adjusted ORs of having reduced eGFR, with ORs of 4.227 (1.681, 10.627) and 3.442 (1.685–7.031) for males and females respectively. AUC of CMI was revealed to be 0.633 (0.620–0.646) in males and 0.684 (0.672–0.695) in females. Conclusions Higher CMI was independently associated with greater burden of reduced eGFR, highlighting VAT distribution and dysfunction as a potential mechanism underlying the association of obesity with kidney damage and adverse cardiovascular outcomes. The findings from this study provided important insights regarding the potential usefulness and clinical relevance of CMI in the detection of reduced eGFR among general Chinese population.https://deepblue.lib.umich.edu/bitstream/2027.42/146138/1/12882_2018_Article_1098.pd

Current Mathematical Methods Used in QSAR/QSPR Studies

This paper gives an overview of the mathematical methods currently used in quantitative structure-activity/property relationship (QASR/QSPR) studies. Recently, the mathematical methods applied to the regression of QASR/QSPR models are developing very fast, and new methods, such as Gene Expression Programming (GEP), Project Pursuit Regression (PPR) and Local Lazy Regression (LLR) have appeared on the QASR/QSPR stage. At the same time, the earlier methods, including Multiple Linear Regression (MLR), Partial Least Squares (PLS), Neural Networks (NN), Support Vector Machine (SVM) and so on, are being upgraded to improve their performance in QASR/QSPR studies. These new and upgraded methods and algorithms are described in detail, and their advantages and disadvantages are evaluated and discussed, to show their application potential in QASR/QSPR studies in the future

Novel Approach Identifies SNPs in SLC2A10 and KCNK9 with Evidence for Parent-of-Origin Effect on Body Mass Index

Marja-Liisa Lokki työryhmien Generation Scotland Consortium, LifeLines Cohort Study ja GIANT Consortium jäsenPeer reviewe

A saturated map of common genetic variants associated with human height

Common single-nucleotide polymorphisms (SNPs) are predicted to collectively explain 40-50% of phenotypic variation in human height, but identifying the specific variants and associated regions requires huge sample sizes(1). Here, using data from a genome-wide association study of 5.4 million individuals of diverse ancestries, we show that 12,111 independent SNPs that are significantly associated with height account for nearly all of the common SNP-based heritability. These SNPs are clustered within 7,209 non-overlapping genomic segments with a mean size of around 90 kb, covering about 21% of the genome. The density of independent associations varies across the genome and the regions of increased density are enriched for biologically relevant genes. In out-of-sample estimation and prediction, the 12,111 SNPs (or all SNPs in the HapMap 3 panel(2)) account for 40% (45%) of phenotypic variance in populations of European ancestry but only around 10-20% (14-24%) in populations of other ancestries. Effect sizes, associated regions and gene prioritization are similar across ancestries, indicating that reduced prediction accuracy is likely to be explained by linkage disequilibrium and differences in allele frequency within associated regions. Finally, we show that the relevant biological pathways are detectable with smaller sample sizes than are needed to implicate causal genes and variants. Overall, this study provides a comprehensive map of specific genomic regions that contain the vast majority of common height-associated variants. Although this map is saturated for populations of European ancestry, further research is needed to achieve equivalent saturation in other ancestries.A large genome-wide association study of more than 5 million individuals reveals that 12,111 single-nucleotide polymorphisms account for nearly all the heritability of height attributable to common genetic variants

A saturated map of common genetic variants associated with human height.

Common single-nucleotide polymorphisms (SNPs) are predicted to collectively explain 40-50% of phenotypic variation in human height, but identifying the specific variants and associated regions requires huge sample sizes1. Here, using data from a genome-wide association study of 5.4 million individuals of diverse ancestries, we show that 12,111 independent SNPs that are significantly associated with height account for nearly all of the common SNP-based heritability. These SNPs are clustered within 7,209 non-overlapping genomic segments with a mean size of around 90 kb, covering about 21% of the genome. The density of independent associations varies across the genome and the regions of increased density are enriched for biologically relevant genes. In out-of-sample estimation and prediction, the 12,111 SNPs (or all SNPs in the HapMap 3 panel2) account for 40% (45%) of phenotypic variance in populations of European ancestry but only around 10-20% (14-24%) in populations of other ancestries. Effect sizes, associated regions and gene prioritization are similar across ancestries, indicating that reduced prediction accuracy is likely to be explained by linkage disequilibrium and differences in allele frequency within associated regions. Finally, we show that the relevant biological pathways are detectable with smaller sample sizes than are needed to implicate causal genes and variants. Overall, this study provides a comprehensive map of specific genomic regions that contain the vast majority of common height-associated variants. Although this map is saturated for populations of European ancestry, further research is needed to achieve equivalent saturation in other ancestries

Negative costimulatory molecule B7-H4 mediates protective effect of mesenchymal stem cells on experimental autoimmune encephalomyelitis

Our previous study has shown that the negative co-stimulatory molecule B7-H4 is constitutively expressed on human bone marrow-derived mesenchymal stem cells (MSCs) and mediates their immunomodulatory effect on T cells in vitro. However, whether B7-H4 on MSCs can be responsible for their immunomodulation in vivo has not been clarified. The present study investigated the immunomodulatory role and mechanism of B7-H4 on mouse mesenchymal stem cell (MSCs) in the development of experimental autoimmune encephalomyelitis (EAE). Murine MSC C3H/10T1/2 (C3H10) cells were transfected with B7-H4-specific shRNA to silence B7-H4 expression (C3H10-B7H4). The effects of C3H10-B7H4 cells on splenocyte proliferation and cell cycling as well as cytokine responses were examined.We found that B7-H4 silencing mitigated the immune-inhibitory effect of C3H10 cells on PHA-stimulated splenocyte activation and proliferation as well as IL-2, IL-17 and IFN-γ responses. Female C57BL/6 mice were injected with myelin oligodendrocyte glycoprotein peptide (MOG35-55) to induce EAE, then infused with C3H10-B7H4, C3H10-NC (C3H10 transfected with negative control shRNA) or C3H10 cells. The pathological changes of the injured spinal cord were analyzed by hematoxylin and eosin (HE) staining, Luxol fast blue (LFB) staining and immunofluorescence. Infusion with C3H10 or C3H10-NC, but not C3H10-B7H4 cells, dramatically slowed the development of EAE, and reduced the severity and degree of inflammatory infiltrates, demyelination, and axonal damages. The plasma levels of interleukin-2 (IL-2), IL-17, interferon-gamma (IFN-γ), and IL-4 in the different groups of mice were examined. Infusion with C3H10 or C3H10-NC cells significantly decreased the plasma levels of IL-2, IL-17 and IFN-γ in EAE mice, but infusion with C3H10-B7H4 cells only slightly reduced pro-inflammatory cytokine responses in mice. Taken together, these data indicated that B7-H4 was important for the immune characteristics and immunomodulatory capacity of mouse MSCs. B7-H4 decreased Th1/Th17 responses in EAE mice. This is the first report on the role and possible mechanism of B7-H4 in the protection of MSCs against MOG-induced EAE in mice. These findings may provide a new avenue and target molecule in MSC-based therapy for autoimmune diseases in the central nervous system, such as multiple sclerosis and neuromyelitis optica spectrum disorder