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Article ; Online: Functional Assessment of High-Risk

Robinson-Cohen, Cassianne

Clinical journal of the American Society of Nephrology : CJASN

2022 Volume 17, Issue 5, Page(s) 626–627

MeSH term(s)	Humans ; Apolipoprotein L1/genetics ; Proteomics ; Kidney ; Genetic Variation
Chemical Substances	Apolipoprotein L1 ; APOL1 protein, human
Language	English
Publishing date	2022-04-26
Publishing country	United States
Document type	Editorial ; Comment
ZDB-ID	2226665-3
ISSN	1555-905X ; 1555-9041
ISSN (online)	1555-905X
ISSN	1555-9041
DOI	10.2215/CJN.03470322
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Article ; Online: Mendelian randomization and the association of fibroblast growth factor-23 with heart failure with preserved ejection fraction.

Akwo, Elvis A / Robinson-Cohen, Cassianne

Current opinion in nephrology and hypertension

2023 Volume 32, Issue 4, Page(s) 305–312

Abstract: Purpose of review: Observational data provide compelling evidence for elevated fibroblast growth factor-23 (FGF23) as a risk factor for heart failure (HF), particularly heart failure with preserved ejection fraction (HFpEF). Given the limitations of ... ...

Abstract	Purpose of review: Observational data provide compelling evidence for elevated fibroblast growth factor-23 (FGF23) as a risk factor for heart failure (HF), particularly heart failure with preserved ejection fraction (HFpEF). Given the limitations of observational studies, uncertainties persist regarding the causal role of FGF23 in the pathogenesis of HF and HFpEF. Recently, Mendelian randomization (MR) studies have been performed to examine causal associations between FGF23 and HF phenotypes. Recent findings: The current review describes the methodological basis of the MR techniques used to examine the causal role of FGF23 on HF phenotypes, highlighting the importance of large-scale multiomics data. The findings from most of the MR studies indicate an absence of evidence of a causal effect of FGF23 on the risk of HF in general population settings. However, analysis using individual-level data showed a strong association between genetically-predicted FGF23 and HFpEF in individuals with a genetic predisposition to low estimated glomerular filtration (eGFR). Summary: Evidence from MR analysis suggests a causal role of FGF23 in the pathogenesis of HFpEF in low eGFR settings - a finding supported by experimental, clinical, and epidemiological data. While future MR studies of FGF23 and HFpEF could provide further evidence, randomized trials of FGF23-lowering agents could provide the most definitive answers on the association in chronic kidney disease populations.
MeSH term(s)	Humans ; Heart Failure/epidemiology ; Heart Failure/genetics ; Stroke Volume ; Fibroblast Growth Factor-23 ; Mendelian Randomization Analysis ; Risk Factors
Chemical Substances	Fibroblast Growth Factor-23 (7Q7P4S7RRE)
Language	English
Publishing date	2023-03-20
Publishing country	England
Document type	Review ; Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	1151092-4
ISSN	1473-6543 ; 1535-3842 ; 1062-4813 ; 1062-4821
ISSN (online)	1473-6543 ; 1535-3842
ISSN	1062-4813 ; 1062-4821
DOI	10.1097/MNH.0000000000000888
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Zs.A 3686: Show issues

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Article ; Online: Genetic variants of mineral metabolism in health and disease.

Robinson-Cohen, Cassianne

Current opinion in nephrology and hypertension

2020 Volume 29, Issue 4, Page(s) 387–393

Abstract: Purpose of review: Disturbances in mineral metabolism are common among individuals with chronic kidney disease and have consistently been associated with cardiovascular and bone disease. The current review aims to describe the current knowledge of the ... ...

Abstract	Purpose of review: Disturbances in mineral metabolism are common among individuals with chronic kidney disease and have consistently been associated with cardiovascular and bone disease. The current review aims to describe the current knowledge of the genetic aspects of mineral metabolism disturbances and to suggest directions for future studies to uncover the cause and pathogenesis of chronic kidney disease - mineral bone disorder. Recent findings: The most severe disorders of mineral metabolism are caused by highly penetrant, rare, single-gene disruptive mutations. More recently, genome-wide association studies (GWAS) have made an important contribution to our understanding of the genetic determinants of circulating levels of 25-hydroxyvitamin D, calcium, phosphorus, fibroblast growth factor-23, parathyroid hormone, fetuin-A and osteoprotegerin. Although the majority of these genes are known members of mineral homeostasis pathways, GWAS with larger sample sizes have enabled the discovery of many genes not known to be involved in the regulation of mineral metabolism. Summary: GWAS have enabled remarkable developments in our ability to discover the genetic basis of mineral metabolism disturbances. Although we are far from using these findings to inform clinical practice, we are gaining understanding of novel biological mechanisms and providing insight into ethnic variation in these traits.
MeSH term(s)	Genetic Variation ; Genome-Wide Association Study ; Humans ; Metabolism, Inborn Errors/genetics ; Metabolism, Inborn Errors/metabolism ; Minerals/metabolism ; Renal Insufficiency, Chronic/genetics ; Renal Insufficiency, Chronic/metabolism
Chemical Substances	Minerals
Language	English
Publishing date	2020-07-01
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Review
ZDB-ID	1151092-4
ISSN	1473-6543 ; 1535-3842 ; 1062-4813 ; 1062-4821
ISSN (online)	1473-6543 ; 1535-3842
ISSN	1062-4813 ; 1062-4821
DOI	10.1097/MNH.0000000000000612
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Article: Multi-trait Analysis of GWAS for circulating FGF23 Identifies Novel Network Interactions Between HRG-HMGB1 and Cardiac Disease in CKD.

Perwad, Farzana / Akwo, Elvis A / Vartanian, Nicholas / Suva, Larrry J / Friedman, Peter A / Robinson-Cohen, Cassianne

medRxiv : the preprint server for health sciences

2024

Abstract: Background: Genome-wide association studies (GWAS) have identified numerous genetic loci associated with mineral metabolism (MM) markers but have exclusively focused on single-trait analysis. In this study, we performed a multi-trait analysis of GWAS ( ... ...

Abstract	Background: Genome-wide association studies (GWAS) have identified numerous genetic loci associated with mineral metabolism (MM) markers but have exclusively focused on single-trait analysis. In this study, we performed a multi-trait analysis of GWAS (MTAG) of MM, exploring overlapping genetic architecture between traits, to identify novel genetic associations for fibroblast growth factor 23 (FGF23). Methods: We applied MTAG to genetic variants common to GWAS of 5 genetically correlated MM markers (calcium, phosphorus, FGF23, 25-hydroxyvitamin D (25(OH)D) and parathyroid hormone (PTH)) in European-ancestry subjects. We integrated information from UKBioBank GWAS for blood levels for phosphate, 25(OH)D and calcium (n=366,484), and CHARGE GWAS for PTH (n=29,155) and FGF23 (n=16,624). We then used functional genomics to model interactive and dynamic networks to identify novel associations between genetic traits and circulating FGF23. Results: MTAG increased the effective sample size for all MM markers to n=50,325 for FGF23. After clumping, MTAG identified independent genome-wide significant SNPs for all traits, including 62 loci for FGF23. Many of these loci have not been previously reported in single-trait analyses. Through functional genomics we identified Histidine-rich glycoprotein ( Conclusion: Our findings highlight the importance of MTAG analysis of MM markers to boost the number of genome-wide significant loci for FGF23 to identify novel genetic traits. Functional genomics revealed novel networks that inform unique cellular functions and identified
Language	English
Publishing date	2024-03-06
Publishing country	United States
Document type	Preprint
DOI	10.1101/2024.03.04.24303051
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Article ; Online: Genetic Variants Associated With Systolic Blood Pressure in Children and Adolescents.

Pike, Mindy M / Schildcrout, Jonathan / Baldwin, Scott / Edwards, Todd / Lipworth, Loren / Robinson-Cohen, Cassianne

Journal of the American Heart Association

2023 Volume 12, Issue 3, Page(s) e027993

Abstract: Background Genetics, along with lifestyle and behavioral characteristics, play an important role in hypertension in adults. Our aim was to identify genetic variants associated with blood pressure in childhood and adolescence. Methods and Results We ... ...

Abstract	Background Genetics, along with lifestyle and behavioral characteristics, play an important role in hypertension in adults. Our aim was to identify genetic variants associated with blood pressure in childhood and adolescence. Methods and Results We conducted a candidate single-nucleotide polymorphism (SNP) analysis and genome-wide association study among 9778 participants aged <18 years in BioVU, the Vanderbilt University Medical Center biobank. The outcome was childhood blood pressure percentile from age 0 to 18 years. For the candidate SNP analysis, a total of 457 previously identified SNPs were examined. Linear regression was used to test the association between genetic variants and median systolic blood pressure (SBP) percentile. Adjusted models included median age, self-reported sex, race, the first 4 principal components of ancestry, and median body mass index
MeSH term(s)	Adolescent ; Child ; Child, Preschool ; Humans ; Blood Pressure/genetics ; Genome-Wide Association Study ; Hypertension/diagnosis ; Hypertension/epidemiology ; Hypertension/genetics ; Linear Models ; Plasma Membrane Calcium-Transporting ATPases/genetics ; Polymorphism, Single Nucleotide ; Risk Factors
Chemical Substances	ATP2B1 protein, human ; Plasma Membrane Calcium-Transporting ATPases (EC 3.6.3.8)
Language	English
Publishing date	2023-01-31
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	2653953-6
ISSN	2047-9980 ; 2047-9980
ISSN (online)	2047-9980
ISSN	2047-9980
DOI	10.1161/JAHA.122.027993
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Article ; Online: Infection risk associated with clonal hematopoiesis of indeterminate potential is partly mediated by hematologic cancer transformation in the UK Biobank.

Vlasschaert, Caitlyn / Akwo, Elvis / Robinson-Cohen, Cassianne / Cook, Elina K / Lanktree, Matthew B / Rauh, Michael J / Bick, Alexander G

Leukemia

2023 Volume 37, Issue 11, Page(s) 2306–2308

MeSH term(s)	Humans ; Clonal Hematopoiesis ; Biological Specimen Banks ; Hematologic Neoplasms/genetics ; Hematopoiesis/genetics ; Disease Susceptibility ; United Kingdom/epidemiology ; Mutation
Language	English
Publishing date	2023-09-09
Publishing country	England
Document type	Letter
ZDB-ID	807030-1
ISSN	1476-5551 ; 0887-6924
ISSN (online)	1476-5551
ISSN	0887-6924
DOI	10.1038/s41375-023-02023-7
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Zs.A 2295: Show issues

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Article ; Online: The association of post-traumatic stress disorder with glomerular filtration rate decline.

Koraishy, Farrukh M / Cohen, Beth E / Scherrer, Jeffery F / Whooley, Mary / Hajagos, Janos / Robinson-Cohen, Cassianne / Hou, Wei

Nephrology (Carlton, Vic.)

2023 Volume 28, Issue 3, Page(s) 181–186

Abstract: While major depression is known to be associated with glomerular filtration rate (GFR) decline, there is a lack of data on the association of other mental illnesses like posttraumatic stress disorder (PTSD) with kidney disease. In 640 adult participants ... ...

Abstract	While major depression is known to be associated with glomerular filtration rate (GFR) decline, there is a lack of data on the association of other mental illnesses like posttraumatic stress disorder (PTSD) with kidney disease. In 640 adult participants of the Heart and Soul Study (mean baseline age of 66.2 years) with a high prevalence cardiovascular disease, hypertension and diabetes, we examined the association of PTSD with GFR decline over a 5-year follow-up. We observed a significantly greater estimated (e) GFR decline over time in those with PTSD compared to those without (2.97 vs. 2.11 ml/min/1.73 m
MeSH term(s)	Adult ; Middle Aged ; Humans ; Aged ; Glomerular Filtration Rate ; Stress Disorders, Post-Traumatic/epidemiology ; Diabetes Mellitus/epidemiology ; Hypertension/epidemiology ; Comorbidity ; Disease Progression
Language	English
Publishing date	2023-01-20
Publishing country	Australia
Document type	Journal Article
ZDB-ID	1303661-0
ISSN	1440-1797 ; 1320-5358
ISSN (online)	1440-1797
ISSN	1320-5358
DOI	10.1111/nep.14140
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Zs.A 4822: Show issues

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Article ; Online: Epigenetic profiling reveals key genes and cis-regulatory networks specific to human parathyroids.

Jung, Youngsook Lucy / Zhao, Wenping / Li, Ian / Jain, Dhawal / Epstein, Charles B / Bernstein, Bradley E / Parangi, Sareh / Sherwood, Richard / Robinson-Cohen, Cassianne / Hsu, Yi-Hsiang / Park, Peter J / Mannstadt, Michael

Nature communications

2024 Volume 15, Issue 1, Page(s) 2106

Abstract: In all terrestrial vertebrates, the parathyroid glands are critical regulators of calcium homeostasis and the sole source of parathyroid hormone (PTH). Hyperparathyroidism and hypoparathyroidism are clinically important disorders affecting multiple ... ...

Abstract	In all terrestrial vertebrates, the parathyroid glands are critical regulators of calcium homeostasis and the sole source of parathyroid hormone (PTH). Hyperparathyroidism and hypoparathyroidism are clinically important disorders affecting multiple organs. However, our knowledge regarding regulatory mechanisms governing the parathyroids has remained limited. Here, we present the comprehensive maps of the chromatin landscape of the human parathyroid glands, identifying active regulatory elements and chromatin interactions. These data allow us to define regulatory circuits and previously unidentified genes that play crucial roles in parathyroid biology. We experimentally validate candidate parathyroid-specific enhancers and demonstrate their integration with GWAS SNPs for parathyroid-related diseases and traits. For instance, we observe reduced activity of a parathyroid-specific enhancer of the Calcium Sensing Receptor gene, which contains a risk allele associated with higher PTH levels compared to the wildtype allele. Our datasets provide a valuable resource for unraveling the mechanisms governing parathyroid gland regulation in health and disease.
MeSH term(s)	Animals ; Humans ; Calcium/metabolism ; Parathyroid Glands/metabolism ; Parathyroid Hormone/genetics ; Parathyroid Hormone/metabolism ; Chromatin/genetics ; Epigenesis, Genetic
Chemical Substances	Calcium (SY7Q814VUP) ; Parathyroid Hormone ; Chromatin
Language	English
Publishing date	2024-03-07
Publishing country	England
Document type	Journal Article
ZDB-ID	2553671-0
ISSN	2041-1723 ; 2041-1723
ISSN (online)	2041-1723
ISSN	2041-1723
DOI	10.1038/s41467-024-46181-3
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Article ; Online: Risk factors for hip and vertebral fractures in chronic kidney disease: the CRIC study.

Hsu, Simon / Bansal, Nisha / Denburg, Michelle / Ginsberg, Charles / Hoofnagle, Andrew N / Isakova, Tamara / Ix, Joachim H / Robinson-Cohen, Cassianne / Wolf, Myles / Kestenbaum, Bryan R / de Boer, Ian H / Zelnick, Leila R

Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research

2024

Abstract: Fracture risk is high in chronic kidney disease (CKD) and underlying pathophysiology and risk factors may differ from the general population. In a cohort study of 3939 participants in the Chronic Renal Insufficiency Cohort (CRIC), we used Cox regression ... ...

Abstract	Fracture risk is high in chronic kidney disease (CKD) and underlying pathophysiology and risk factors may differ from the general population. In a cohort study of 3939 participants in the Chronic Renal Insufficiency Cohort (CRIC), we used Cox regression to test associations of putative risk factors with the composite of first hip or vertebral fracture assessed using hospital discharge codes. Mean age was 58 years, 45% were female, 42% were Black, and 13% were Hispanic. There were 82 hip and 24 vertebral fractures over a mean (SD) 11.1 (4.8) years (2.4 events per 1000 person-years [95% CI: 2.0, 2.9]). Measured at baseline, diabetes, lower body mass index (BMI), steroid use, proteinuria, and elevated parathyroid hormone (PTH) were each associated with fracture risk after adjusting for covariates. Lower time-updated estimated glomerular filtration rate (eGFR) was associated with fractures (HR 1.20 per 10 mL/min/1.73m2 lower eGFR; 95% CI: 1.04, 1.38) as were lower time-updated serum calcium and bicarbonate concentrations. Among time-updated categories of kidney function, hazard ratios (95% CI) for incident fracture were 4.53 (1.77, 11.60) for kidney failure treated with dialysis and 2.48 (0.86, 7.14) for post-kidney transplantation, compared with eGFR ≥60. Proton pump inhibitor use, dietary calcium intake, measures of vitamin D status, serum phosphate, urine calcium and phosphate, and plasma fibroblast growth factor-23 were not associated with fracture risk. In conclusion, lower eGFR in CKD is associated with higher fracture risk, which was highest in kidney failure. Diabetes, lower BMI, steroid use, proteinuria, higher serum concentrations of PTH, and lower calcium and bicarbonate concentrations were associated with fractures and may be modifiable risk factors.
Language	English
Publishing date	2024-02-04
Publishing country	England
Document type	Journal Article
ZDB-ID	632783-7
ISSN	1523-4681 ; 0884-0431
ISSN (online)	1523-4681
ISSN	0884-0431
DOI	10.1093/jbmr/zjae021
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Zs.A 2142: Show issues

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Article ; Online: 75561 Association of childhood hypertension with early adulthood obesity and hypertension

Mindy Pike / T. Alp Ikizler / Loren Lipworth / Cassianne Robinson-Cohen

Journal of Clinical and Translational Science, Vol 5, Pp 31-

2021 Volume 32

Abstract: ABSTRACT IMPACT: This study establishes the association between childhood hypertension and health outcomes in early adulthood, identifying the need to understand blood pressure during early life for primary prevention of hypertension and cardiovascular ... ...

Abstract	ABSTRACT IMPACT: This study establishes the association between childhood hypertension and health outcomes in early adulthood, identifying the need to understand blood pressure during early life for primary prevention of hypertension and cardiovascular disease. OBJECTIVES/GOALS: There is evidence that blood pressure level in early life can influence hypertension and other cardiovascular risk factors later in life. We examined whether hypertension before the age of 18 is associated with higher odds of obesity and hypertension after the age of 18. METHODS/STUDY POPULATION: We studied 19,367 children and adolescents from the Vanderbilt University Medical Center’s Synthetic Derivative, a de-identified version of the electronic medical record. Childhood hypertension was defined as systolic blood pressure (SBP) ≥130 mmHg or diastolic blood pressure (DBP) ≥80 mmHg at three or more outpatient visits before the age of 18. Obesity and hypertension in early adulthood were the primary outcomes. Obesity was defined as being above normal weight for adulthood height at age 30 based on the NIH’s body mass index tables. Hypertension was defined as SBP ≥130 mmHg or DBP ≥80 mmHg at three or more outpatient visits after the age of 18. Odds ratios and 95% confidence intervals (CIs) were computed from logistic regression models adjusted for demographics, medication use, and childhood weight. RESULTS/ANTICIPATED RESULTS: Most subjects were female (63%) and white (80%). During childhood, 17% of participants had hypertension. Approximately 58% of this group were obese at age 30, and 38% had hypertension as adults. Compared to females with no childhood hypertension, females with childhood hypertension had 1.35 times higher odds of being obese at age 30 (95% CI: 1.15, 1.58) and 3.56 times higher odds of having hypertension over the age of 18 (95% CI: 3.09, 4.09). Males with childhood hypertension, compared to males without, had 1.28 times higher odds of being obese at age 30 (95% CI: 1.08, 1.52) and 2.74 times higher odds of having ...
Keywords	Medicine ; R
Subject code	610
Language	English
Publishing date	2021-03-01T00:00:00Z
Publisher	Cambridge University Press
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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