Nora Franceschini

Nora Franceschini
University of North Carolina at Chapel Hill | UNC · Department of Epidemiology

MD MPH FAHA

About

666
Publications
53,002
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22,302
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Introduction
I am a board certified nephrologist and a genetic epidemiologist. My research includes social, environmental and biological determinants of kidney disease and hypertension in multi-ethnic populations using tools from epidemiology and genetics.
Additional affiliations
June 2007 - present
University of North Carolina at Chapel Hill
Position
  • Professor

Publications

Publications (666)
Article
Full-text available
Here, we report a lack of diversity in epigenome-wide association studies (EWAS) and DNA methylation (DNAm) data, discuss current challenges, and propose solutions for EWAS and DNAm research in diverse populations. The strategies we propose include fostering community involvement, new data generation, and cost-effective approaches such as locus-spe...
Article
Background In response to the COVID-19 pandemic, public health measures, including stay-at-home orders, were widely instituted in the United States (US) by March 2020. However, few studies have evaluated the impact of these measures on continuity of care among older adults living with chronic diseases. Methods Beginning in June 2020, participants...
Article
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Dyslipidemia associates with and usually precedes the onset of chronic kidney disease (CKD), but a comprehensive assessment of molecular lipid species associated with risk of CKD is lacking. Here, we sought to identify fasting plasma lipids associated with risk of CKD among American Indians in the Strong Heart Family Study, a large-scale community-...
Preprint
Chronic kidney disease (CKD) is prevalent in Central America and ancestry-specific factors may contribute to CKD risk. To understand the genetic ancestry influences on CKD susceptibility, we conducted an admixture mapping of CKD traits and risk factors on 1,023 participants of the Hispanic Community Health Study/Study of Latinos who reported four-g...
Article
Recent work has highlighted a lack of diversity in genomic studies. However, less attention has been given to epigenomics. Here, we show that epigenomic studies are lacking in diversity and propose several solutions to address this problem.
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Clinical and biomarker phenotypic associations for carriers of protein function-altering variants may help to elucidate gene function and health effects in populations. We genotyped 1127 Strong Heart Family Study participants for protein function-altering single nucleotide variants (SNV) and indels selected from a low coverage whole exome sequencin...
Article
Background: The availability of whole-genome sequencing data in large studies has enabled the assessment of coding and noncoding variants across the allele frequency spectrum for their associations with blood pressure. Methods: We conducted a multiancestry whole-genome sequencing analysis of blood pressure among 51 456 Trans-Omics for Precision...
Article
Hypertension is a major cardiovascular disease risk factor and contributor to premature death globally. Family-based investigations confirmed a significant heritable component of blood pressure (BP) while genome-wide association studies revealed >1000 common and rare genetic variants associated with BP and/or hypertension. The kidney is not only an...
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In a multi-stage analysis of 52,436 individuals aged 17-90 across diverse cohorts and biobanks, we train, test, and evaluate a polygenic risk score (PRS) for hypertension risk and progression. The PRS is trained using genome-wide association studies (GWAS) for systolic, diastolic blood pressure, and hypertension, respectively. For each trait, PRS i...
Preprint
Aims To provide a comprehensive evaluation of the biomedical effects of circulating concentrations of cholesterol-containing lipoproteins and apolipoproteins. Methods and Results Nuclear magnetic resonance (NMR) spectroscopy was used to measure the cholesterol content of high density (HDL-C), very low-density (VLDL-C), intermediate-density (IDL-C),...
Article
Numerous genes for monogenic kidney diseases with classical patterns of inheritance, as well as genes for complex kidney diseases that manifest in combination with environmental factors, have been discovered. Genetic findings are increasingly used to inform clinical management of nephropathies, and have led to improved diagnostics, disease surveill...
Article
Introduction: Blood pressure (BP) is known to rise during developmental stages from childhood to adulthood, and that those with higher BP trajectories are more likely to develop hypertension and CVD. Yet, there is a paucity of studies that have evaluated trajectories of BP change or the genetic factors involved in the BP changes from childhood to a...
Article
Background: Apparent treatment-resistant hypertension (aTRH) is characterized by the use of four or more antihypertensive classes to achieve blood pressure (BP) control. The estimated prevalence of aTRH from population-based studies is ~12-15% among adults with hypertension (HTN). Individuals with aTRH have an increased risk for cardiovascular even...
Article
Introduction: Despite the high prevalence of chronic kidney disease (CKD) in the Hispanic/Latino population, most Hispanic/Latino adults with CKD are not aware. This study aims to develop a tool for the Hispanic/Latino population to determine whether an individual has CKD. Methods: Baseline (2008-2011) data on 13,636 participants (aged 18 – 74 year...
Article
Background: Dyslipidemia is associated with and often precedes the onset of chronic kidney disease (CKD). However, standard lipid panels fail to describe the full spectrum of blood lipidome. A longitudinal profiling of the full spectrum of blood lipidome associated with the risk of CKD is still lacking in any racial/ethnic group, including American...
Preprint
African Americans (AAs) experience a high burden of hypertension but have been underrepresented in genetic studies of blood pressure. We performed common and rare variant genome-wide association studies (GWAS) of systolic (SBP) and diastolic (DBP) blood pressure, pulse pressure and hypertension in 95,457 AAs from the Million Veteran Program and Con...
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Background While large genome-wide association studies have identified nearly one thousand loci associated with variation in blood pressure, rare variant identification is still a challenge. In family-based cohorts, genome-wide linkage scans have been successful in identifying rare genetic variants for blood pressure. This study aims to identify lo...
Preprint
Dysfunction of either the right or left ventricle can lead to heart failure (HF) and subsequent morbidity and increased mortality. We performed a genome-wide association study (GWAS) of 16 measurements of biventricular function and structure obtained from cardiac magnetic resonance (CMR). We then used aggregated data from three independent plasma p...
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Background Genome-wide association study (GWAS) single nucleotide polymorphisms (SNPs) are known to preferentially co-locate to active regulatory elements in tissues and cell types relevant to disease aetiology. Further characterisation of associated cell type-specific regulation can broaden our understanding of how GWAS signals may contribute to d...
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Background The difference between an individual's chronological and DNA methylation predicted age (DNAmAge), termed DNAmAge acceleration (DNAmAA), can capture life-long environmental exposures and age-related physiological changes reflected in methylation status. Several studies have linked DNAmAA to morbidity and mortality, yet its relationship wi...
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Background United States (US) Hispanic/Latinos experience a disproportionate burden of obesity, which may in part be related to demographic or sociocultural factors, including acculturation to an US diet or inactive lifestyle. Therefore, we sought to describe the association between adulthood weight histories and demographic and sociocultural facto...
Article
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Long and short sleep duration are associated with elevated blood pressure (BP), possibly through effects on molecular pathways that influence neuroendocrine and vascular systems. To gain new insights into the genetic basis of sleep-related BP variation, we performed genome-wide gene by short or long sleep duration interaction analyses on four BP tr...
Preprint
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Background: We used summary statistics from previously-published GWAS of systolic and diastolic BP and of hypertension to construct Polygenic Risk Scores (PRS) to predict hypertension across diverse populations. Methods: We used 10,314 participants of diverse ancestry from BioMe to train trait-specific PRS. We implemented a novel approach to select...
Article
Circulating metabolites are by-products of endogenous metabolism or exogenous sources and may inform disease states. Our study aimed to identify the source of variability in the association of metabolites with estimated glomerular filtration rate (eGFR) in Hispanics/Latinos with low chronic kidney disease prevalence and tested the association of 64...
Article
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Viral infections, including hepatitis C, can cause secondary glomerular nephropathies. Studies suggest that hepatitis C virus infection (HCV+) is a risk factor for chronic kidney disease (CKD) but evidence of this relationship is lacking among Hispanics/Latinos. We examined the association between HCV+ and incident CKD in a prospective cohort of Hi...
Article
Background suPAR (Soluble urokinase plasminogen activator receptor) has emerged as an important biomarker of coagulation, inflammation, and cardiovascular disease (CVD) risk. The contribution of suPAR to CVD risk and its genetic influence in the Black population have not been evaluated. Methods We measured suPAR in 3492 Blacks from the prospective...
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Background: This study was to systematically test whether previously reported risk factors for chronic kidney disease (CKD) are causally related to CKD in European and East Asian ancestries using Mendelian randomization. Methods: A total of 45 risk factors with genetic data in European ancestry and 17 risk factors in East Asian participants were...
Article
Despite the high prevalence and economic burden of chronic kidney disease (CKD), federal funding for kidney-related research, prevention, and education activities under the National Institute of Diabetes, Digestive and Kidney Diseases (NIDDK) remains substantially lower compared to other chronic diseases. More federal support is needed to promote c...
Article
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Development of cholesteryl ester transfer protein (CETP) inhibitors for coronary heart disease (CHD) has yet to deliver licensed medicines. To distinguish compound from drug target failure, we compared evidence from clinical trials and drug target Mendelian randomization of CETP protein concentration, comparing this to Mendelian randomization of pr...
Preprint
Full-text available
We developed novel closed-form estimators of genetic and environmental correlation coefficients. We applied them to estimate over 4,000 genetic and environmental correlations between multiple phenotypes in a diverse sample from the Trans-Omics in Precision Medicine (TOPMed) program. We found substantial differences in heritabilities, genetic, and e...
Article
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Reproductive longevity is essential for fertility and influences healthy ageing in women1,2, but insights into its underlying biological mechanisms and treatments to preserve it are limited. Here we identify 290 genetic determinants of ovarian ageing, assessed using normal variation in age at natural menopause (ANM) in about 200,000 women of Europe...
Article
Despite the dramatic underrepresentation of non-European populations in human genetics studies, researchers continue to exclude participants of non-European ancestry, as well as variants rare in European populations, even when these data are available. This practice perpetuates existing research disparities and can lead to important and large effec...
Preprint
Gene-lifestyle interaction analyses have identified genetic variants whose effect on cardiovascular risk-raising traits is modified by alcohol consumption and smoking behavior. The biological mechanisms of these interactions remain largely unknown, but may involve epigenetic modification linked to perturbation of gene expression. Diverse, individua...
Article
Background - Coronary artery calcification (CAC) and carotid artery intima-media thickness (cIMT) are measures of subclinical atherosclerosis in asymptomatic individuals and strong risk factors for cardiovascular disease (CVD). Type 2 diabetes (T2D) is an independent CVD risk factor that accelerates atherosclerosis. Methods - We performed meta-anal...
Article
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Rationale and Objective Apolipoprotein L1 (APOL1) high-risk variants are associated with an increased risk of chronic kidney disease (CKD) among African Americans. Less is known regarding the risk of development of CKD and kidney failure (ESKD) among African Americans with only one APOL1 risk variant or whether the risk is modified by sickle cell t...
Article
Study question: Does the expansion of genome-wide association studies (GWAS) to a broader range of ancestries improve the ability to identify and generalise variants associated with age at menarche (AAM) in European populations to a wider range of world populations? Summary answer: By including women with diverse and predominantly non-European a...
Preprint
Background Admixture mapping is a powerful approach for gene mapping of complex traits that leverages the diverse genetic ancestry in populations with recent admixture such as U.S. Hispanics/Latinos (HL), who have increased risk of chronic kidney disease (CKD). Methods Genome-wide admixture mapping was performed for CKD and estimated glomerular fi...
Article
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Background DNA methylation (DNAm) is associated with gene regulation and estimated glomerular filtration rate (eGFR), a measure of kidney function. Decreased eGFR is more common among US Hispanics and African Americans. The causes for this are poorly understood. We aimed to identify trans-ethnic and ethnic-specific differentially methylated positio...
Article
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Genotype-phenotype association studies often combine phenotype data from multiple studies to increase power. Harmonization of the data usually requires substantial effort due to heterogeneity in phenotype definitions, study design, data collection procedures, and data set organization. Here we describe a centralized system for phenotype harmonizati...
Article
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Background Genome-wide association studies (GWAS) of kidney function have uncovered hundreds of loci, primarily in populations of European ancestry. We have undertaken the first continental African GWAS of estimated glomerular filtration rate (eGFR), a measure of kidney function used to define chronic kidney disease (CKD). Method We conducted GWAS...
Article
Objective: To identify causal pathophysiological mechanisms for atherosclerosis and incident cardiovascular events using protein measurements. Approach and Results: Carotid artery atherosclerosis was assessed by ultrasound, and 86 cardiovascular-related proteins were measured using the Olink CVD-I panel in 7 Swedish prospective studies (11 754 ind...
Article
Full-text available
The Trans-Omics for Precision Medicine (TOPMed) programme seeks to elucidate the genetic architecture and biology of heart, lung, blood and sleep disorders, with the ultimate goal of improving diagnosis, treatment and prevention of these diseases. The initial phases of the programme focused on whole-genome sequencing of individuals with rich phenot...
Article
Genetic effects are suspected to influence cadmium internal dose. Our objective was to assess genetic determinants of urine cadmium in American Indian adults participating in the Strong Heart Family Study (SHFS). Urine cadmium levels and genotyped short tandem repeat (STR) markers were available on 1936 SHFS participants. We investigated heritabili...
Article
Full-text available
Objective We employed Mendelian randomization (MR) to explore the effects of genetic predisposition to type 2 diabetes (T2D), hyperglycemia, insulin resistance, and β-cell dysfunction on risk of stroke subtypes and related cerebrovascular phenotypes. Methods We selected instruments for genetic predisposition to T2D (74,124 cases, 824,006 controls)...
Preprint
Full-text available
Reproductive longevity is critical for fertility and impacts healthy ageing in women, yet insights into the underlying biological mechanisms and treatments to preserve it are limited. Here, we identify 290 genetic determinants of ovarian ageing, assessed using normal variation in age at natural menopause (ANM) in ~200,000 women of European ancestry...
Article
Full-text available
Background Genetic factors that influence kidney traits have been understudied for low frequency and ancestry-specific variants. Methods We combined whole genome sequencing (WGS) data from 23,732 participants from 10 NHLBI Trans-Omics for Precision Medicine (TOPMed) Program multi-ethnic studies to identify novel loci for estimated glomerular filtr...
Article
Full-text available
Importance The incidence of and mortality from coronary heart disease (CHD) are substantially higher among African American individuals compared with non-Hispanic White individuals, even after adjusting for traditional factors associated with CHD. The unexplained excess risk might be due to genetic factors related to African ancestry that are assoc...
Article
Background This study was to systematically test whether previously reported risk factors for chronic kidney disease (CKD) are causally related to CKD in European and East Asian ancestries using Mendelian randomization. Methods A total of 45 risk factors with genetic data in European ancestry and 17 risk factors in East Asian participants were ide...
Article
Background There is accumulating evidence linking prolonged sedentary time to adverse health outcomes. The effect of sedentary behavior on kidney function has not been evaluated in US Hispanics/Latinos, a population disproportionately affected by CKD. Methods We evaluated the association between accelerometer-measured (1 week) sedentary time at ba...
Article
Full-text available
Genetic studies of blood pressure (BP) to date have mainly analyzed common variants (minor allele frequency > 0.05). In a meta-analysis of up to ~1.3 million participants, we discovered 106 new BP-associated genomic regions and 87 rare (minor allele frequency ≤ 0.01) variant BP associations (P < 5 × 10⁻⁸), of which 32 were in new BP-associated loci...
Article
Full-text available
Genetic studies of blood pressure (BP) to date have mainly analyzed common variants (minor allele frequency > 0.05). In a meta-analysis of up to ~1.3 million participants, we discovered 106 new BP-associated genomic regions and 87 rare (minor allele frequency ≤ 0.01) variant BP associations (P < 5 × 10−8), of which 32 were in new BP-associated loci...
Article
Sickle cell disease (SCD) and apolipoprotein L1 (APOL1) G1/G2 variants increase chronic kidney disease (CKD) risk in African Americans by poorly understood mechanisms. We applied bioinformatics to identify new candidate genes associated with SCD‐related CKD. An interaction network demonstrated APOA1 connecting haemoglobin subunit β (HBB) and APOL1...
Article
Full-text available
Background: Hypertension has been implicated as a smoking-related risk factor for cardiovascular disease but the dose-response relationship is incompletely described. Hispanics, who often have relatively light smoking exposures, have been understudied in this regard. Methods: We used data from a six-year follow up study of US Hispanic adults age...
Preprint
Full-text available
Background: Drug development of cholesteryl ester transfer protein (CETP) inhibition to prevent coronary heart disease (CHD) has yet to deliver licensed medicines. To distinguish compound from drug target failure, we compared evidence from clinical trials and Mendelian randomization (MR) results. Methods: Findings from meta-analyses of CETP inhibit...
Preprint
Full-text available
Drug development of cholesteryl ester transfer protein (CETP) inhibition to prevent coronary heart disease (CHD) has yet to deliver licensed medicines. To distinguish compound from drug target failure, we compared evidence from clinical trials and Mendelian randomization (MR) results. Findings from meta-analyses of CETP inhibitor trials (≥ 24 weeks...
Preprint
Full-text available
BACKGROUND The chronic kidney disease (CKD) public health burden is substantial and has not declined as expected with current interventions on disease treatments. A large number of clinical, biological, and behavioural risk factors have been associated with CKD. However, it is unclear which of them are causal. OBJECTIVE To systematically test wheth...
Preprint
Despite the dramatic underrepresentation of non-European populations in human genetics studies, researchers continue to exclude participants of non-European ancestry, even when these data are available. This practice perpetuates existing research disparities and can lead to important and large effect size associations being missed. Here, we conduct...