Background: Decreased renal function is an established risk factor for cardiovascular disease (CVD). Causal mechanisms between estimates of renal function and CVD are intricate and investigation of the relative importance of genetic and environmental factors for the variability of these phenotypes could provide new knowledge.
Methods And Results: Cystatin C and creatinine levels in 12 313 twins were analyzed. Uni- and bivariate heritability for these traits and CVD was estimated through structured equation modelling and genome-wide complex trait analysis (GCTA) in order to independently confirm additive genetic effects. Twin model-estimated heritability of Cystatin C was 0.55 (95% confidence interval [CI], 0.49 to 0.60) in men, 0.63 (0.59 to 0.66) in women, and 0.60 (0.56 to 0.63) in both sexes combined. For creatinine, heritability estimates were in the same range. Heritability of CVD was 0.39 (0.02 to 0.67) in men and 0.20 (0.00 to 0.61) in women. The phenotypic correlation between Cystatin C and CVD correlation was 0.16 (0.12 to 0.20) in men and 0.17 (0.13 to 0.21) in women, whereas the genetic correlation in males was 0.41 (0.21 to 0.62) while it was non-significant in females. Trough GCTA, the heritability of Cystatin C and creatinine in both sexes combined was estimated to 0.40 (SE 0.07, P=8E(-9)) and 0.19 (SE 0.07, P=0.003), respectively.
Conclusions: Twin model-based heritability of Cystatin C was higher compared to previous studies. Co-variation between Cystatin C and CVD in males was partly explained by additive genetic components, indicating that Cystatin C and CVD share genetic influences. The GCTA provided independent evidence for significant contribution of additive genetics to trait variance of Cystatin C.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4330070 | PMC |
| http://dx.doi.org/10.1161/JAHA.114.001467 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Key Points: We found that development of both albuminuria and reduced eGFR was associated with clinically significant cognitive decline, particularly in the psychomotor and mental efficiency domain. There was also a significant interaction between worsened albuminuria and eGFR, the combination of which augmented cognitive deficits. A more comprehensive longitudinal phenotype of albuminuria showed that regressed albuminuria did not associate with worsened cognitive decline, as opposed to persistent albuminuria.
View Article and Find Full Text PDFOver the past few decades, obesity has become a public health issue of global concern. Even though disparities exist between human populations, , the higher liver fat content of the Japanese despite a lower body mass index (BMI), studies on the genetics of obesity still largely focus on populations of European descent, leading to a dearth of genetic data on non-European populations. In this context, this study aimed to establish a broad picture of the genetic attributes of the Japanese population, by examining a representative sample of 18,889 individuals participating in the Tohoku Medical Megabank Project cohort.
View Article and Find Full Text PDFGenetic and Environmental Influences on the Correlations between Traits of Metabolic Syndrome and CKD.
Clin J Am Soc Nephrol
November 2019
Department of Clinical Science and Education, Karolinska Institute; and.
Background And Objectives: Metabolic syndrome is a cluster of risk factors associated with CKD. By studying the genetic and environmental influences on how traits of metabolic syndrome correlate with CKD, the understanding of the etiological relationships can be improved.
Design, Setting, Participants, & Measurements: From the population-based TwinGene project within the Swedish Twin Registry, 4721 complete twin pairs (9442 European ancestry participants) were included in this cross-sectional twin study.
The Central Role of KNG1 Gene as a Genetic Determinant of Coagulation Pathway-Related Traits: Exploring Metaphenotypes.
PLoS One
July 2017
Unit of Genomics of Complex Diseases, Sant Pau Institute of Biomedical Research (IIB-Sant Pau), Barcelona, Spain.
Traditional genetic studies of single traits may be unable to detect the pleiotropic effects involved in complex diseases. To detect the correlation that exists between several phenotypes involved in the same biological process, we introduce an original methodology to analyze sets of correlated phenotypes involved in the coagulation cascade in genome-wide association studies. The methodology consists of a two-stage process.
View Article and Find Full Text PDFCystatin C in aging and in Alzheimer's disease.
Ageing Res Rev
December 2016
Departments of Psychiatry, New York University School of Medicine, USA; Biochemistry and Molecular Pharmacology, New York University School of Medicine, USA; Center for Dementia Research, Nathan S. Kline Institute, Orangeburg, NY 10962, USA. Electronic address:
Under normal conditions, the function of catalytically active proteases is regulated, in part, by their endogenous inhibitors, and any change in the synthesis and/or function of a protease or its endogenous inhibitors may result in inappropriate protease activity. Altered proteolysis as a result of an imbalance between active proteases and their endogenous inhibitors can occur during normal aging, and such changes have also been associated with multiple neuronal diseases, including Amyotrophic Lateral Sclerosis (ALS), rare heritable neurodegenerative disorders, ischemia, some forms of epilepsy, and Alzheimer's disease (AD). One of the most extensively studied endogenous inhibitor is the cysteine-protease inhibitor cystatin C (CysC).
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!