Valerio Napolioni

Valerio Napolioni
University of Camerino | UNICAM · School of Biosciences and Veterinary Medicine

Ph.D
Head of Genomic and Molecular Epidemiology (GAME) Lab.

About

150
Publications
31,351
Reads
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2,585
Citations
Introduction
My large and solid expertise in Genomic and Molecular Epidemiology is leading myself to tackle a myriad of different scientific issues, from human X-chromosome analysis to PanGenome analysis of clinically-relevant bacterial species, and from global evolutionary/human adaptation-related issues to the genome-wide analysis of neuropsychiatric traits. Currently, I'm leading the Genomic And Molecular Epidemiology (GAME) lab at the School of Biosciences and Veterinary Medicine, University of Camerino.
Additional affiliations
February 2015 - December 2019
Stanford University
Position
  • Instructor
April 2013 - September 2014
Università degli Studi di Perugia
Position
  • Next-Gen Sequencing core, Lead Scientist
September 2011 - October 2012
Translational Genomics Research Institute
Position
  • PostDoc Position

Publications

Publications (150)
Article
Full-text available
We report a genome-wide association study (GWAS) of coronary artery disease (CAD) incorporating nearly a quarter of a million cases, in which existing studies are integrated with data from cohorts of white, Black and Hispanic individuals from the Million Veteran Program. We document near equivalent heritability of CAD across multiple ancestral grou...
Article
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Remdesivir is the first US Food and Drug Administration (FDA)‐approved drug for the treatment of coronavirus disease 2019 (COVID‐19). We conducted a retrospective pharmacogenetic study to examine remdesivir‐associated liver enzyme elevation among Million Veteran Program participants hospitalized with COVID‐19 between March 15, 2020, and June 30, 20...
Article
Importance: The APOE ε2 and APOE ε4 alleles are the strongest protective and risk-increasing, respectively, genetic variants for late-onset Alzheimer disease (AD). However, the mechanisms linking APOE to AD-particularly the apoE protein's role in AD pathogenesis and how this is affected by APOE variants-remain poorly understood. Identifying missen...
Article
Full-text available
Background Genetic variants within the APOE locus may modulate Alzheimer’s disease (AD) risk independently or in conjunction with APOE *2/3/4 genotypes. Identifying such variants and mechanisms would importantly advance our understanding of APOE pathophysiology and provide critical guidance for AD therapies aimed at APOE . The APOE locus however re...
Article
Full-text available
Objectives The F386L PSEN1 variant has been reported in 1 Japanese family with limited clinical information. We aimed to prove that F386L is pathogenic by demonstrating that it segregates with early-onset Alzheimer disease (AD). Methods Eight individuals in a South Asian family provided DNA for genetic testing and underwent a neurologic examinatio...
Article
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We describe the clinical and neuropathologic features of patients with Lewy body spectrum disorder (LBSD) carrying a nonsense variant, c.604C>T; p.R202X, in the glucocerebrosidase 1 (GBA) gene. While this GBA variant is causative for Gaucher’s disease, the pathogenic role of this mutation in LBSD is unclear. Detailed neuropathologic evaluation was...
Article
Full-text available
GWASs have identified numerous genetic variants associated with a wide variety of diseases, yet despite the wide availability of genetic testing the insights that would enhance the interpretability of these results are not widely available to members of the public. As a proof of concept and demonstration of technological feasibility, we developed P...
Article
Full-text available
Background Acute or chronic irreversible respiratory failure may occur in patients undergoing pneumonectomy. Aim of this study was to determine transcriptome expression changes after experimental pneumonectomy in swine model. Experimental left pneumonectomy was performed in five pigs under general anaesthesia. Both the resected and the remaining lu...
Article
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Background: Damaging rare variants in the TREM2, SORL1 and ABCA7 genes have been associated with an increased risk of developing Alzheimer's Disease (AD) with odds ratios that were not observed since the identification of the main AD genetic risk factor, the APOE-ε4 allele. Here, we aimed to identify additional AD-associated genes by investigating...
Article
Background: APOE*4 is the strongest genetic risk factor for late-onset Alzheimer's disease (AD) and is highly pleiotropic, such that it may be considered as a biological factor that can affect overall genetic risk for AD. To advance our understanding of the genetic architecture of AD, we sought to perform the largest APOE*4-stratified genome-wide...
Article
Background: The increased risk of Alzheimer's Disease (AD) with age is well established. However, genome-wide association studies of AD have often wrongly accounted for this known effect by covarying by age using age-at-onset for cases and age-at-last-exam for controls. In most scenarios, this leads to controls being on average older than cases an...
Article
Background: Among Alzheimer's Disease (AD) tier 1 genes, BIN1 shows the greatest sex-biased expression in GTEx RNASeq, notably in brain tissues. Fine-mapping studies suggest that the BIN1 locus harbors at least two independent risk variants. Method: We considered a region ±200kb around BIN1 and performed sex-stratified analyses to identify genom...
Article
Background: Rare variants are hypothesized to contribute greatly to the "missing heritability" in AD. APOE*4 is the strongest genetic risk factor for late-onset AD. As such, older, cognitively normal APOE*4 carriers may harbor rare protective variants. We prioritized candidate variants in families based on their segregation with protected APOE*4 c...
Preprint
Full-text available
Whole-exome sequencing (WES) and whole-genome sequencing (WGS) are expected to be critical to further elucidate the missing genetic heritability of Alzheimer’s disease (AD) risk by identifying rare coding and/or noncoding variants that contribute to AD pathogenesis. In the United States, the Alzheimer’s Disease Sequencing Project (ADSP) has taken a...
Preprint
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BACKGROUND The APOE gene has two common missense variants that greatly impact the risk of late-onset Alzheimer's disease (AD). Here we examined the risk of a third APOE missense variant, R145C, that is rare in European-Americans but present in 4% of African-Americans and always in phase with APOE ϵ3. METHODS In this study, we included 11,790 indivi...
Preprint
Full-text available
Background: Genetic variants within the APOE locus may modulate Alzheimer′s disease (AD) risk independently or in conjunction with APOE*2/3/4 genotypes. Identifying such variants and mechanisms would importantly advance our understanding of APOE pathophysiology and provide critical guidance for AD therapies aimed at APOE. The APOE locus however rem...
Preprint
GWASs have identified numerous genetic variants associated with a wide variety of diseases, yet despite the wide availability of genetic testing the insights that would enhance the interpretability of these results are not widely available to members of the public. As a proof of concept and demonstration of technological feasibility, we developed P...
Article
Full-text available
Extreme longevity in humans has a strong genetic component, but whether this involves genetic variation in the same longevity pathways as found in model organisms is unclear. Using whole-exome sequences of a large cohort of Ashkenazi Jewish centenarians to examine enrichment for rare coding variants, we found most longevity-associated rare coding v...
Article
Full-text available
Aims: The aim of this work was to refine the taxonomy and the functional characterization of publicly available Lactiplantibacillus plantarum complete genomes through a pan-genome analysis. Particular attention was paid in depicting the probiotic potential of each strain. Methods and results: Complete genome sequence of 127 L. plantarum strains,...
Article
Evaluating gene by environment (G$\times$E) interaction under an additive risk model (i.e. additive interaction) has gained wider attention. Recently, statistical tests have been proposed for detecting additive interaction that utilize an assumption on G-E independence to boost power, which do not rely on restrictive genetic models such as dominant...
Article
Full-text available
Background Many Alzheimer’s disease (AD) genetic association studies disregard age or incorrectly account for it, hampering variant discovery. Methods Using simulated data, we compared the statistical power of several models: logistic regression on AD diagnosis adjusted and not adjusted for age; linear regression on a score integrating case-contro...
Preprint
Full-text available
Coronary artery disease (CAD) is a leading cause of death, yet its genetic determinants are not fully elucidated. We report a multi-ethnic genome-wide association study of CAD involving nearly a quarter of a million cases, incorporating the largest cohorts to date of Whites, Blacks, and Hispanics from the Million Veteran Program with existing studi...
Article
Objective: To examine whether amyloid PET in CN individuals that were screened for the Anti-Amyloid in Asymptomatic AD (A4) study differed across self-identified, non-Hispanic White and Black (NHW and NHB) groups. Methods: We examined 3689 NHW and 144 NHB that passed initial screening for the A4 study and underwent amyloid PET. The effect of rac...
Article
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More than 50% of all gynecologic tumors can be classified as rare (defined as an incidence of ≤6 per 100,000 women) and usually have a poor prognosis owing to delayed diagnosis and treatment. In contrast to almost all other common solid tumors, the treatment of rare gynecologic tumors (RGT) is often based on expert opinion, retrospective studies, o...
Article
Objective Identify genetic variants on the X‐chromosome associated with Parkinson's disease (PD) risk. Methods We performed an X‐chromosome‐wide association study (XWAS) of PD risk by meta‐analyzing results from sex‐stratified analyses. To avoid spurious associations, we designed a specific harmonization pipeline for the X‐chromosome and focused o...
Article
Full-text available
Abstract: More than 50% of all gynecologic tumors can be classified as rare (defined as an incidence of ≤6 per 100,000 women) and usually have a poor prognosis owing to delayed diagnosis and treatment. In contrast to almost all other common solid tumors, the treatment of rare gynecologic tumors (RGT) is often based on retrospective studies, expert...
Article
Full-text available
Prior work in late-onset Alzheimer’s disease (LOAD) has resulted in discrepant findings as to whether recent consanguinity and outbred autozygosity are associated with LOAD risk. In the current study, we tested the association between consanguinity and outbred autozygosity with LOAD in the largest such analysis to date, in which 20 LOAD GWAS datase...
Article
KLOTHO*VS heterozygosity (KL*VSHET+) was recently shown to be associated with reduced risk of Alzheimer’s disease (AD) in APOE*4 carriers. Additional studies suggest that KL*VSHET+ protects against amyloid burden in cognitively normal older subjects, but sample sizes were too small to draw definitive conclusions. We performed a well-powered meta-an...
Article
Full-text available
State-of-the-art rare variant association testing methods aggregate the contribution of rare variants in biologically relevant genomic regions to boost statistical power. However, testing single genes separately does not consider the complex interaction landscape of genes, nor the downstream effects of non-synonymous variants on protein structure a...
Preprint
Full-text available
Introduction Many Alzheimer's disease (AD) genetic association studies disregard age or incorrectly account for it, hampering variant discovery. Method Using simulated data, we compared the statistical power of several models: logistic regression on AD diagnosis adjusted and not adjusted for age; linear regression on a score integrating case-contro...
Preprint
Full-text available
Objective Identify genetic variants on the X-chromosome associated with Parkinson’s disease (PD) risk. Methods We performed an X-chromosome-wide association study (XWAS) of PD risk by meta-analyzing results from sex-stratified analyses. To avoid spurious associations, we designed a specific harmonization pipeline for the X-chromosome and focused o...
Article
The identification of rare haplotypes may greatly expand our knowledge in the genetic architecture of both complex and monogenic traits. To this aim, we developed PERHAPS (Paired-End short Reads-based HAPlotyping from next-generation Sequencing data), a new and simple approach to directly call haplotypes from short-read, paired-end Next Generation...
Article
Common genetic polymorphisms identified by genome wide association explain less than half the genetic variance of Alzheimer’s disease (AD). Rare genetic mutations with larger effect sizes than common variants are expected to contribute to this missing heritability. We developed an extreme phenotype filtering‐based approach to identify rare candidat...
Article
Klotho‐VS heterozygosity (KL‐VSHET) has been linked to increased longevity and decreased rate of cognitive decline. In Alzheimer’s disease (AD), KL‐VSHET was recently shown to decrease both AD risk and amyloid burden, specifically, in APOE4+ controls of Northwestern European descent within the age range of 60 to 80 years (Belloy et al., 2020). We i...
Article
Posterior cortical atrophy (PCA) is a rare early‐onset form of dementia, typically due to Alzheimer’s disease (PCA‐AD) characterised by predominant deficits of higher‐order visual functions, with relatively preserved memory, verbal fluency and insight with respect to typical, amnestic AD (tAD). A prior genetic study by Schott et al. (2016) investig...
Article
Are there genetic variants in the APOE locus that alter APOE4‐related risk for AD? Do these putative variants exert their effect through altering availability of the APOE protein? With these questions in mind, we investigated whether the APOE splice quantitative trait loci (sQTL; variants that alter post‐transcriptional splicing) affect risk for AD...
Preprint
Full-text available
The amygdala is one of the most widely connected structures in the primate brain and plays a key role in social and emotional behavior. Here, we present the first genome-wide association study (GWAS) of whole-brain resting-state amygdala networks to discern whether connectivity in these networks could serve as an endophenotype for social behavior....
Article
Full-text available
Several statistical methods have been proposed for testing gene(G)-environment(E) interactions under additive risk models using genome-wide association study data. However, these approaches have strong assumptions on underlying genetic models such as dominant or recessive effects that are known to be less robust when the true genetic model is unkno...
Article
Question: Does Klotho-VS heterozygosity protect against Alzheimer disease (AD) in individuals who carry APOE4? Findings: In this study, associations were evaluated across 22 AD cohorts (n = 20 928), 3 longitudinal cohorts (n = 3008), and 4 cohorts collecting β-amyloid measurements (cerebrospinal fluid, n = 556; brain, n = 251). In individuals who...
Article
Over the coming decade, much more genetic data will enter into the study of economic development. This paper provides an example and emphasizes the uses and misuses of such information. It has assembled for the first time national frequencies of the ACP1 genetic polymorphism and the Interleukin-6 (IL6-174G) and Interleukin-10 (IL10-1082G) cytokines...
Article
Full-text available
The World Health Organization has identified antimicrobial resistance as a substantial threat to human health. Because of the emergence of pathogenic bacteria resistant to multiple antibiotics worldwide, there is a need to identify the mode of action of antibiotics and to unravel the basic mechanisms responsible for drug resistance. Antibiotic prod...
Preprint
Full-text available
Background: State-of-the-art rare variant association testing methods aggregate the contribution of rare variants in biologically relevant genomic regions to boost statistical power. However, testing single genes separately does not consider the complex interaction landscape of genes, nor the downstream effects of non-synonymous variants on protein...
Article
Full-text available
We report here the draft genome sequence of Streptomyces sp. strain AM-2504, a microorganism producing a broad range of biotechnologically relevant molecules. The comparative analysis of its 16S rRNA sequence allowed the assignment of this strain to the Streptomyces kasugaensis species, thus fostering functional characterization of the secondary me...
Article
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Aspergillus is the causative agent of human diseases ranging from asthma to invasive infection. Genetic and environmental factors are crucial in regulating the interaction between the host and Aspergillus. The role played by the enzyme indoleamine 2,3-dioxygenase 1 (IDO1), which catalyzes the first and rate-limiting step of tryptophan catabolism al...
Article
Alzheimer’s disease (AD) is considered a polygenic disorder. This view is clouded, however, by lingering uncertainty over how to treat the quasi “monogenic” role of apolipoprotein E (APOE). The APOE4 allele is not only the strongest genetic risk factor for AD, it also affects risk for cardiovascular disease, stroke, and other neurodegenerative diso...
Article
Full-text available
Background: Opioids are widely used for chronic low back pain (CLBP); however, it is still unclear how to predict their effectiveness and safety. Codeine, tramadol and oxycodone are metabolized by CYP/CYP450 2D6 (CYP2D6), a highly polymorphic enzyme linked to allele-specific related differences in metabolic activity. Purpose: CYP2D6 genetic poly...
Article
Mitochondrial crista structure partitions vital cellular reactions and is precisely regulated by diverse cellular signals. Here, we show that, in Drosophila, mitochondrial cristae undergo dynamic remodeling among distinct subcellular regions and the Parkinson's disease (PD)-linked Ser/Thr kinase PINK1 participates in their regulation. Mitochondria...
Article
Objectives: A reduction in glucose metabolism in the posterior cingulate cortex (PCC) predicts conversion to Alzheimer's disease (AD) and tracks disease progression, signifying its importance in AD. We aimed to use decline in PCC glucose metabolism as a proxy for the development and progression of AD to discover common genetic variants associated...
Article
Historical pathogen burdens are examined as possible triggers for genetic adaptation. Evidence of adaptation emerges for the acid phosphatase locus 1 (ACP1), interleukin-6 (IL6), interleukin-10 (IL10 ), human leukocyte antigen (HLA) polymorphisms, along with a measure of heterozygosity over 783 alleles. Results are robust to controlling for the phy...
Article
The nicotinic system plays an important role in cognitive control and is implicated in several neuropsychiatric conditions. However, the contributions of genetic variability in this system to individuals’ cognitive control abilities are poorly understood and the brain processes that mediate such genetic contributions remain largely unidentified. In...
Article
Background: The well-known insertion/deletion polymorphism (rs4646994) of the angiotensin-converting enzyme (ACE) gene has been previously associated with obesity, blood flow, muscular strength, and ACE enzyme activity. Despite the relevant role of ACE in homeostasis, few data are currently available on the relationship between rs4646994 and hydra...
Article
Pediatric obesity develops when a complex biological predisposition collides with an obesogenic environment. To further elucidate the role of genetics in obesity onset, we performed a candidate-gene association study in a young and sportive Italian population by testing the association of functional polymorphisms in ACE (rs4646994), FTO (rs9939609)...
Article
T helper 9 (Th9) cells contribute to lung inflammation and allergy as sources of interleukin-9 (IL-9). However, the mechanisms by which IL-9/Th9 mediate immunopathology in the lung are unknown. Here we report an IL-9-driven positive feedback loop that reinforces allergic inflammation. We show that IL-9 increases IL-2 production by mast cells, which...
Data
Supplementary Figures 1-8, Supplementary Tables 1-6 and Supplementary References.