Browsing by Author "Edenberg, H. J."

Now showing 1 - 2 of 2
  • Thumbnail Image
    Item
    Fibroblast Growth Factor 23 Genotype and Cardiovascular Disease in Patients Undergoing Hemodialysis
    (Karger Publishers, 2019-02) Schwantes-An, T.-H.; Liu, S.; Stedman, M.; Decker, B. S.; Wetherill, L.; Edenberg, H. J.; Vatta, M.; Foroud, T. M.; Chertow, G. M.; Moe, S. M.; Medical and Molecular Genetics, School of Medicine
    Background: Elevated serum concentrations of fibroblast growth factor 23 (FGF23) are associated with cardiovascular mortality in patients with chronic kidney disease and those undergoing dialysis. Objectives: We tested the hypotheses that polymorphisms in FGF23, its co-receptor alpha-klotho (KL), and/or FGF23 receptors (FGFR) are associated with cardiovascular events and/or mortality. Methods: We used 1,494 DNA samples collected at baseline from the Evaluation of Cinacalcet HCl Therapy to Lower Cardiovascular Events Trial, in which patients were randomized to the calcimimetic cinacalcet or placebo for the treatment of secondary hyperparathyroidism. We analyzed European and African Ancestry samples separately and then combined summary statistics to perform a meta-analysis. We evaluated single-nucleotide polymorphisms (SNPs) in FGF23, KL, and FGFR4 as the key exposures of interest in proportional hazards (Cox) regression models using adjudicated endpoints (all-cause and cardiovascular mortality, sudden cardiac death, and heart failure [HF]) as the outcomes of interest. Results: rs11063112 in FGF23 was associated with cardiovascular mortality (risk allele = A, hazard ratio [HR] 1.32, meta-p value = 0.004) and HF (HR 1.40, meta-p value = 0.007). No statistically significant associations were observed between FGF23 rs13312789 and SNPs in FGFR4 or KL genes and the outcomes of interest. Conclusions: rs11063112 was associated with HF and cardiovascular mortality in patients receiving dialysis with moderate to severe secondary hyperparathyroidism.
  • Thumbnail Image
    Item
    Genetic influences on eight psychiatric disorders based on family data of 4 408 646 full and half-siblings, and genetic data of 333 748 cases and controls
    (Cambridge University Press, 2018-09) Pettersson, E.; Lichtenstein, P.; Larsson, H.; Song, J.; Attention Deficit/Hyperactivity Disorder Working Group of the iPSYCH-Broad-PGC Consortium; Agrawal, A.; Børglum, A. D.; Bulik, C. M.; Daly, M. J.; Davis, L. K.; Demontis, D.; Edenberg, H. J.; Grove, J.; Gelernter, J.; Neale, B. M.; Pardiñas, A. F.; Stahl, E.; Walters, J. T. R.; Walters, R.; Sullivan, P. F.; Posthuma, D.; Polderman, T. J. C.; Biochemistry and Molecular Biology, School of Medicine
    BackgroundMost studies underline the contribution of heritable factors for psychiatric disorders. However, heritability estimates depend on the population under study, diagnostic instruments, and study designs that each has its inherent assumptions, strengths, and biases. We aim to test the homogeneity in heritability estimates between two powerful, and state of the art study designs for eight psychiatric disorders.MethodsWe assessed heritability based on data of Swedish siblings (N = 4 408 646 full and maternal half-siblings), and based on summary data of eight samples with measured genotypes (N = 125 533 cases and 208 215 controls). All data were based on standard diagnostic criteria. Eight psychiatric disorders were studied: (1) alcohol dependence (AD), (2) anorexia nervosa, (3) attention deficit/hyperactivity disorder (ADHD), (4) autism spectrum disorder, (5) bipolar disorder, (6) major depressive disorder, (7) obsessive-compulsive disorder (OCD), and (8) schizophrenia.ResultsHeritability estimates from sibling data varied from 0.30 for Major Depression to 0.80 for ADHD. The estimates based on the measured genotypes were lower, ranging from 0.10 for AD to 0.28 for OCD, but were significant, and correlated positively (0.19) with national sibling-based estimates. When removing OCD from the data the correlation increased to 0.50.ConclusionsGiven the unique character of each study design, the convergent findings for these eight psychiatric conditions suggest that heritability estimates are robust across different methods. The findings also highlight large differences in genetic and environmental influences between psychiatric disorders, providing future directions for etiological psychiatric research.