Flavio De Angelis

The Neolithic site of Piano dei Cardoni (Ustica, Palermo) and the chronology of Sicily between the mid-6th and the end of the 5th millennium BCE - Eight new radiocarbon dates obtained on fauna (Ovis/ Capra) and human bones from the Piano dei Cardoni site (Ustica, Palermo) are presented. The island was occupied during the Neolithic period due to its...

Even though agriculture already spread into Eurasia during the Neolithic, the transition between the Copper Age and the Bronze Age was the time where Italian communities tuned horticultural techniques to foster the soil productivity. Carbon and nitrogen stable isotope analyses could be leveraged to identify some of those practices, such as manuring...

Purpose Coding mutations in the Transthyretin (TTR) gene cause a hereditary form of amyloidosis characterized by a complex genotype-phenotype correlation with limited information regarding differences among worldwide populations. Methods We compared 676 diverse individuals carrying TTR amyloidogenic mutations (rs138065384, Phe44Leu; rs730881165, A...

Hearing difficulty (HD) is one of the major health burdens in older adults. While aging-related changes in the peripheral auditory system play an important role, genetic variation associated with brain structure and function could also be involved in HD predisposition. We analyzed a large-scale HD genome-wide association study (GWAS; Ntotal = 501,8...

Background: Hearing difficulty (HD) is one of the major health burdens in older adults. While aging-related changes in the peripheral auditory system play an important role, genetic variation associated with brain structure and function could also be involved in HD predisposition. Methods: We analyzed a large-scale HD genome-wide association study...

This study focuses on the changes in diet and mobility of people buried in the La Sassa cave (Latium, Central Italy) during the Copper and Bronze Ages to contribute to the understanding of the complex contemporary population dynamics in Central Italy. To that purpose, carbon and nitrogen stable isotope analyses, strontium isotope analyses, and FT-I...

Background The Million Veteran Program (MVP) participants represent 100 years of US history, including significant social and demographic changes over time. Our study assessed two aspects of the MVP: (i) longitudinal changes in population diversity and (ii) how these changes can be accounted for in genome-wide association studies (GWAS). To investi...

Background Hearing problems (HP) in adults are common and are associated with several comorbid conditions. Its prevalence increases with age, reflecting the cumulative effect of environmental factors and genetic predisposition. Although several risk loci have been already identified, HP biology and epidemiology are still insufficiently investigated...

Background: Little is known about environmental factors that may influence associations between genetic liability to suicidality and suicidal behavior. Methods: This study examined whether a suicidality polygenic risk score (PRS) derived from a large genome-wide association study (N = 122,935) was associated with suicide attempts in a population...

Background Introgression from extinct Neanderthal and Denisovan human species has been shown to contribute to the genetic pool of modern human populations and their phenotypic spectrum. Evidence of how Neanderthal introgression shaped the genetics of human traits and diseases has been extensively studied in populations of European descent, with sig...

The Pastena cave is located in central Italy, and its best-preserved sector is Grotticella W2, which is dated radiometrically to the Early-Middle Bronze Age. The aim of this paper is to explore human diet, animal husbandry, and plant management, analysing the findings there discovered. Carbon and nitrogen stable isotope analysis was carried out on...

Forensic DNA phenotyping (FDP) provides the ability to predict the human external traits from unknown sample donors, directly from minute amounts of DNA found at the crime scene. We developed a MPS multiplex assay, with the aim of genotyping all 41 DNA markers included in the HIrisPlex-S system for simultaneous prediction of eye, hair and skin colo...

The research project Diseases, health and lifestyles in Rome: from the Empire to the Early Middle Age (PRIN 2015), covered a significant area of research, ranging from the historical and historico-medical content that emerged during the multi-disciplinary investigation on the subject, to the intersection between different methods and approaches and...

Objective Archeological excavations in the area of the “Parco archeologico di Ostia antica” uncovered human remains requiring radiological insight to clarify the etiology of multiple morphological alterations. The purpose of this paper was to analyze CT findings of the remains, to push forward the contribution of CT in anthropological analysis. Ma...

Background Due to its large impact on human health, socio-economic status (SES) could at least partially influence the established association between obesity and coronavirus disease 2019 (COVID-19) severity. To estimate the independent effect of body size and SES on the clinical manifestations of COVID-19, we conducted a Mendelian randomization (M...

Importance: Certain psychiatric and immune-related disorders are reciprocal risk factors. However, the nature of these associations is unclear. Objective: To characterize the pleiotropy between psychiatric and immune-related traits, as well as risk factors of hypothesized relevance. Design, setting, and participants: This genetic association s...

Daniel Tylee gave an oral presentation characterizing results of an investigation of genetic correlations and causal inference effects (i.e., Mendelian randomization) between a large set of psychiatric and immune-related phenotypes, including allergic, autoimmune, inflammatory disorders, as well as a set of hypothesized confounding phenotypes (e.g....

The Pastena cave is located in central Italy and its best-preserved sector is Grotticella W2, which is dated radiometrically to the Early-Middle Bronze Age. The aim of this paper is to explore human diet, animal husbandry, and plant management analyzing the findings there discovered. Carbon and nitrogen stable isotope analysis have been carried out...

UK Biobank (UKB) is a key contributor in mental health genome-wide association studies (GWAS) but only ~31% of participants completed the Mental Health Questionnaire (“MHQ responders”). We predicted generalized anxiety disorder (GAD), posttraumatic stress disorder (PTSD), and major depression symptoms using elastic net regression in the ~69% of UKB...

Posttraumatic stress disorder (PTSD) is a psychiatric disorder that may arise in response to severe traumatic event and is diagnosed based on three main symptom clusters (reexperiencing, avoidance, and hyperarousal) per the Diagnostic Manual of Mental Disorders (version DSM-IV-TR). In this study, we characterized the biological heterogeneity of PTS...

Polygenic risk scores (PRS) may help inform the etiology of suicidal thoughts and behaviors. In this study, we evaluated whether a suicidality PRS derived from a large genome-wide association study (GWAS) of suicidality from the UK Biobank (N = 122,935) predicted suicidal ideation (SI) in a 7-year population-based, prospective cohort of European-Am...

We conducted a comprehensive genome-wide investigation of hearing loss (HL) in 748,668 adult participants of the UK Biobank, the Nurses Health Studies (I and II), the Health Professionals Follow-up Study, and the Million Veteran Program. We identified 54 risk loci and characterized HL polygenic architecture, exploring sex differences, polygenic ris...

The global need to monitor the status of marine resources is a priority task in marine management, but most ocean surveys still rely on costly and time-consuming capture-based techniques. Here we test a novel, easy-to use device to collect eDNA on board of bottom trawl fishing vessels, during normal fishing operations, quickly and easily: custom-ma...

The Million Veteran Program (MVP) participants represent 100 years of US history, including significant social and demographic change over time. Our study assessed two aspects of the MVP: (i) longitudinal changes in population diversity and (ii) how these changes can be accounted for in genome-wide association studies (GWAS). The MVP was divided in...

This paper aims to provide a first glimpse into the genomic characterization of individuals buried in Casal Bertone (Rome, first–third centuries AD) to gain preliminary insight into the genetic makeup of people who lived near a tannery workshop, fullonica. Therefore, we explored the genetic characteristics of individuals who were putatively recruit...

Transthyretin (TTR) is the precursor of the fibrils that compromise organ function in hereditary and sporadic systemic amyloidoses (ATTR). RNA-interference and anti-sense therapeutics targeting TTR hepatic transcription have been shown to reduce TTR amyloid formation. In the present study, we leveraged genetic and phenotypic information from the UK...

Risk factors and long-term consequences of COVID-19 infection are unclear but can be investigated with large-scale genomic data. To distinguish correlation from causation, we performed in-silico analyses of three COVID-19 outcomes (N > 1,000,000). We show genetic correlation and putative causality with depressive symptoms, metformin use (genetic ca...

Alcohol drinking and tobacco smoking are hazardous behaviors associated with a wide range of adverse health outcomes. In this study, we explored the association of polygenic risk scores (PRS) related to drinks per week, age of smoking initiation, smoking initiation, cigarettes per day, and smoking cessation with 433 psychiatric and behavioral trait...

The mobility patterns in the Italian peninsula during prehistory are still relatively unknown. The excavation of the Copper Age and Bronze Age deposits in La Sassa cave (Sonnino, Italy) allowed to broaden the knowledge about some local and regional dynamics. We employed a multi-disciplinary approach, including stable (carbon and nitrogen, C and N,...

Angiotensin-converting enzyme-2 (ACE2) receptor has been identified as the key adhesion molecule for the transmission of the SARS-CoV-2. However, there is no evidence that human genetic variation in ACE2 is singularly responsible for COVID-19 susceptibility. Therefore, we performed an integrative multi-level characterization of genes that interact...

Evidence of how human evolution shaped the polygenicity of human traits and diseases has been extensively studied in populations of European descent. However, limited information is currently available about its impact on other ancestry groups. Here, we investigated how different evolutionary processes affected the common variant heritability of tr...

Background: Transthyretin (TTR) is a multi-function protein involved in the systemic transport of retinol and thyroxine. It also participates in the neuronal response to stress and proteolysis of few specific substrates. TTR is also the precursor of the fibrils that compromise organ function in the familial and sporadic systemic amyloidoses (ATTR)....

UK Biobank (UKB) is a key contributor in mental health genome-wide association studies (GWAS) but only ~31% of participants completed the Mental Health Questionnaire ( MHQ responders ). We predicted generalized anxiety disorder (GAD), posttraumatic stress disorder (PTSD), and major depression symptoms using elastic net regression in the ~69% of UKB...

Caves are one of the most conservative environments on Earth, where archaeological, anthropological, climatic and tectonic data can be well-preserved. Here, we present the results of a multidisciplinary method that allowed us to recognize, for the first time in this area, the interaction between Late Pleistocene to Anthropocene neotectonic and arch...

The present research investigates the relationship between dietary habits and mortality patterns in the Roman Imperial and Medieval periods. The reconstructions of population dynamics and subsistence strategies provide a fascinating source of information for understanding our history. This is particularly true given that the changes in social, econ...

Background Obesity has been associated with more severe clinical manifestations of coronavirus disease 2019 (COVID-19). However, this association can be affected by many correlates of these traits. Due to its large impact on human health, socioeconomic status (SES) could at least partially influence the association between obesity and COVID-19 seve...

A recent preventive archaeological survey at the Fara Sabina Railway Station in Passo Corese (Rieti) conduced by the SABAP-LAZ, brought to light a necropolis pertaining to 42 tombs dated back to 1 st-3 rd century AD. This area played an outstanding economic and political role in ancient times as it was crossed by the Tiber River and the via Salaria...

Microbes inhabit different anatomical sites of the human body including oral cavity, gut, and skin. A growing literature highlights how microbiome variation is associated with human health and disease. There is strong evidence of bidirectional communication between gut and brain mediated by neurotransmitters and microbial metabolites. Here, we revi...

Across Europe, the genetics of the Chalcolithic/Bronze Age transition is increasingly characterized in terms of an influx of Steppe-related ancestry. The effect of this major shift on the genetic structure of populations in the Italian Peninsula remains underexplored. Here, genome-wide shotgun data for 22 individuals from commingled cave and single...

To investigate cross-ancestry genetics of complex traits, we conducted a phenome-wide analysis of loci with heterogeneous effects across African, Admixed-American, Central/South Asian, East Asian, European, and Middle Eastern participants of UK Biobank (N = 441 331). Testing 843 phenotypes, we identified 82 independent genomic regions mapping varia...

Background Rome became the prosperous Capital of the Roman Empire through the political and military conquests of neighbouring areas. People were able to move Romeward modifying the Rome area’s demographic structure. However, the genomic evidence for the population of one of the broadest Empires in antiquity has been sparse until recently. Aim The...

The identification of dietary habits is increasingly seen as a fundamental aspect for studying the ancient human populations. Accordingly, several projects aiming to identify Paleolithic individuals’ dietary patterns were developed to analyze the organic component of bone tissue and identify isotopic markers to reconstruct the food typology. Bone f...

Epidemiologic studies recognize that trauma and posttraumatic stress are associated with heightened suicidal behavior severity, yet examination of these associations from a genetic perspective is limited. We performed a multivariate gene-by-environment genome-wide interaction study (GEWIS) of suicidality in 123,633 individuals using a covariance ma...

As a means for investigating human mobility during late the Neolithic to the Copper Age in central and southern Italy, this study presents a novel dataset of enamel oxygen and carbon isotope values (δ18Oca and δ13Cca) from the carbonate fraction of biogenic apatite for one hundred and twenty-six individual teeth coming from two Neolithic and eight...

Background - The Val122Ile mutation in Transthyretin ( TTR ) gene causes a rare, difficult to diagnose hereditary form of cardiac amyloidosis. This mutation is most common in the United States and mainly present in people of African descent. The carriers have an increased risk of congestive heart failure, peripheral edema, and several other non-car...

Hereditary transthyretin (TTR) amyloidosis (hATTR) is a rare life-threatening disorder caused by amyloidogenic coding mutations located in TTR gene. To understand the high phenotypic variability observed among carriers of TTR disease-causing mutations, we conducted an epigenome-wide association study (EWAS) assessing more than 700,000 methylation s...

To distinguish correlation from causation, we performed in-silico analyses of three COVID-19 outcomes (N>1,000,000). We show genetic correlation and putative causality with depressive symptoms, metformin use, and alcohol use. COVID-19 risk loci associated with several hematologic biomarkers. Comprehensive findings inform genetic contributions to CO...

Ancient dental calculus represents one of the most recent and innovative sources of archaeobotanical record. Exploring this matrix, diet, past ecology, and ethnobotanical practices of antique communities may be elucidated. In the present case-study, the tartar of an Imperial Roman man, likely a salt worker, found in the necropolis of Castel Malnome...

Angiotensin-converting enzyme-2 ( ACE2 ) receptor has been identified as the key adhesion molecule for the transmission of the SARS-CoV-2. However, there is no evidence that human genetic variation in ACE2 is singularly responsible for COVID-19 susceptibility. Therefore, we performed a multi-level characterization of genes that interact with ACE2 (...

Background: Alcohol drinking and tobacco smoking are hazardous behaviors associated with a wide range of adverse health outcomes, including many mental and physical disorders. Methods: To investigate the pleiotropic mechanisms linking these traits to cognitive and behavioral development, we explored the association of polygenic risk scores (PRS) re...

This paper aims to provide the isotopic characterization of the diet consumed by people buried in a graveyard of the Imperial Rome Suburbium (1st–3rd centuries CE), where numerous children were buried. A sample of 50 human remains from Quarto Cappello del Prete was selected for carbon and nitrogen stable isotope analysis. Published data related to...

One of the most important Neolithic necropolises in the north-east of the Iberian Peninsula is La Feixa del Moro (3975-3790 cal. BC), located at 1335 mamsl in the Pyrenees (Juberri, Sant Julia de Lòria, Andorra). Within the scarcity of multiple simultaneous Neolithic burials, the main importance of La Feixa del Moro lies in the fact that it is one...

This paper aims to provide a broad diet reconstruction for people buried in archaeologically defined contexts in Rome (first to third centuries CE), in order to combine archaeological and biological evidence focusing on dietary preferences in Imperial Rome. A sample of 214 human bones recovered from 6 funerary contexts was selected for carbon and n...

This paper aims to define the dietary profile of the population of early medieval Rome (fifth–eleventh centuries CE) by carbon and nitrogen stable isotope analysis. This period was characterized by deep changes in the city’s economic, demographic, and social patterns, probably affecting its inhabitants’ nutritional habits. Carbon and nitrogen stabl...

The Transthyretin ( TTR ) Val122Ile mutation causes a rare life-threatening disorder attributable to amyloid deposition. This mutation is mainly present in people of African descent; carriers have an increased risk of congestive heart failure and several other non-cardiac phenotypes such as carpal tunnel syndrome, peripheral edema, and arthroplasty...

Recent strontium isotope (87Sr/86Sr) analyses of bones and teeth have provided useful archeological results for reconstructing past human migration and diet. We report 87Sr/86Sr ratios and DNA analyses of tooth enamel from individuals buried in some necropolises in Nola town, near Napoli (Campania, South Italy). These individuals lived in the perio...

We performed a multivariate gene-by-environment genome-wide interaction study (GEWIS) of suicidality in 123,633 individuals using a covariance matrix based on 26 environments related to traumatic experiences, posttraumatic stress, social support, and socioeconomic status. We discovered sex-specific risk loci exhibiting interaction effects driven by...

The Val122Ile mutation in Transthyretin (TTR) gene causes a rare, difficult to diagnose hereditary form of cardiac amyloidosis. This mutation is most common in the United States and mainly present in people of African descent. The carriers have an increased risk of congestive heart failure and several other non-cardiac phenotypes such as carpal tun...

Hereditary Transthyretin (TTR) Amyloidosis (hATTR) is a rare life-threatening disorder caused by amyloidogenic coding mutations located in TTR gene. To understand the high phenotypic variability observed among carriers of TTR disease-causing mutations, we conducted an epigenome-wide association study (EWAS) assessing more than 700,000 methylation s...

This paper aims to provide a broad diet reconstruction for people buried in archaeologically defined contexts in Rome (1 st -3 rd centuries CE), in order to combine archaeological and biological evidence focusing on dietary preferences in Imperial Rome. A sample of 214 human bones recovered from 6 funerary contexts were selected for carbon and nitr...

Transthyretin (TTR) gene has a causal role in a hereditary form of amyloidosis (ATTRm) and is potentially involved in the risk of wild-type transthyretin amyloidosis (ATTRwt). To understand the genetics of ATTRm and ATTRwt, we conducted a phenome-wide association study of TTR gene in 361,194 participants of European descent testing coding and non-c...

Pigment-related genetic variants point out their role in personal identification as they can be considered predictors suitable for Forensic DNA Phenotyping (FDP) and mounting evidence suggest also their bio-geographic inferential power for gaining information about the individual geographical origin. As they could be regarded as AIMs (Ancestry Info...

The paper aims to point out the subsistence in Eneolithic Central Italian communities by Stable Isotope Analysis. This period marked a tipping point in the food strategies because it was characterized by economic changes and several technological improvements leading to enhance land exploitation and livestock breeding. Carbon and nitrogen stable is...

Transthyretin (TTR) gene has a causal role in a hereditary form of amyloidosis (ATTRm) and is potentially involved in the risk of senile systemic amyloidosis (SSA). To understand the genetics of ATTRm and SSA, we conducted a phenome-wide association study of TTR gene in 361,194 participants of European descent testing coding and non-coding variants...

This survey reports the mitochondrial data of two Spanish populations living in the Vera and Bejar valleys, on the opposite slopes of the Sierra de Gredos (Central Spain), which crosses Spain east to west. The aim of the study was to characterise the mitochondrial genetic pool of the Vera and Bejar populations to investigate a putative mitogenetic...

Context: The Mediterranean area has always played a significant role in human dispersal due to the large number of migratory events contributing to shape the cultural features and the genetic pool of its populations. Objective: This paper aims to review and diachronically describe the mitogenome variability in the Mediterranean population and the m...

Coding mutations in TTR gene cause a rare hereditary form of systemic amyloidosis, which has a complex genotype-phenotype correlation. We investigated the role of non-coding variants in regulating TTR gene expression and consequently amyloidosis symptoms. We evaluated the genotype-phenotype correlation considering the clinical information of 129 It...

Background Transthyretin (TTR) amyloidosis is a hereditary disease with a complex genotype-phenotype correlation. We conducted a literature survey to define the clinical landscape of TTR amyloidosis across populations worldwide. Then, we investigated whether the genetically determined TTR expression differs among human populations, contributing to...

Objectives Analysis of human genetic variation in mountain communities can shed light on the peopling of mountainous regions, perhaps revealing whether the remote geographic location spared them from outside invasion and preserved their gene pool from admixture. In this study, we created a model to assess genetic traces of historical events by reco...

Demography evaluates the traits of human populations mainly by measuring their sizes and fluctuations. Due to their features, the archeological population structures refer to the distribution of people based both on sex and age at death. These parameters have a direct impact on the risk of death because they vary significantly with age and sex and...

Introduction: Transthyretin (TTR)-related amyloidosis is characterized by autosomal transmission of amyloidogenic mutated TTR. Val30Met is one of the most common amyloidogenic TTR mutations, showing a worldwide distribution with phenotypic heterogeneity among human populations. Multiple founder mutations for Val30Met foci have been hypothesized and...