Raquel Cruz

• PhD
• Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER) - USC

The CORDELIA Study (Collaborative Cohorts Reassembled Data to Study Mechanisms and Long-term Incidence of Chronic Diseases) combines 35 Spanish population cohorts to investigate the clinical, environmental, genetic, and omics determinants of cardiovascular disease in the Southern European population. It aims to conduct the largest genome-wide assoc...

Background/Objectives: Fluoropyrimidine derivatives, 5-fluorouracil (5-FU) and its prodrugs (capecitabine and tegafur), are widely used in patients suffering from colorectal cancer. The enzyme responsible for their metabolization, dihydropyrimidine dehydrogenase (DPD), is encoded by the DPYD gene, which is highly polymorphic and may contain polymor...

Background/Objectives: Lactoferrin, a protein involved in the immune response, plays a significant role in the etiopathogenesis of periodontitis in the general population. This cross-sectional study aims to determine the salivary concentration of lactoferrin in Down syndrome individuals with periodontitis. Methods: A convenience cohort of 76 Down s...

Background/Objectives: The COVID-19 pandemic resulted in 675 million cases and 6.9 million deaths by 2022. Despite substantial declines in case fatalities following widespread vaccination campaigns, the threat of future coronavirus outbreaks remains a concern. Current treatments for COVID-19 have been repurposed from existing therapies for other in...

Introduction Acute respiratory distress syndrome (ARDS) is a severe inflammatory process of the lung, often due to sepsis, and poses significant mortality burden in intensive care units. Here we conducted the largest genome-wide association study (GWAS) of sepsis-associated ARDS to identify novel genetic risk loci that can help guide the developmen...

The frequency of mitochondrial DNA haplogroups (mtDNA-HG) in humans is known to be shaped by migration and repopulation. Mounting evidence indicates that mtDNA-HG are not phenotypically neutral, and selection may contribute to its distribution. Haplogroup H, the most abundant in Europe, improved survival in sepsis. Here we developed a random forest...

Individuals diagnosed with functional neurological disorder experience abnormal movement, gait, sensory processing or functional seizures, for which research into the pathophysiology identified psychosocial contributing factors as well as promising biomarkers. Recent pilot studies suggested that (epi-)genetic variants may act as vulnerability facto...

Background Current models on functional neurological disorders (FND) propose a multifactorial origin. Recent studies identified potential biological vulnerability factors such as a reduced limbic volume or an altered stress response. These findings highlight the need to investigate a potential genetic contribution to the biological vulnerability to...

The genetic basis of severe COVID-19 has been thoroughly studied, and many genetic risk factors shared between populations have been identified. However, reduced sample sizes from non-European groups have limited the discovery of population-specific common risk loci. In this second study nested in the SCOURGE consortium, we conducted a genome-wide...

Imatinib is the tyrosine kinase inhibitor used as the gold standard for the treatment of Chronic Myeloid Leukemia. However, about 30% of patients do not respond well to this therapy. Variants in drug administration, distribution, metabolism and excretion (ADME) genes play an important role in drug resistance especially in admixed populations. We in...

The pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2, COVID-19) had an estimated overall case fatality ratio of 1.38% (pre-vaccination), being 53% higher in males and increasing exponentially with age. Among 9578 individuals diagnosed with COVID-19 in the SCOURGE study, we found 133 cases (1.42%) with detectable clonal...

This study explores the genetic factors associated with atypical femoral fractures (AFF), rare fractures associated with prolonged anti-resorptive therapy. AFF are fragility fractures that typically appear in the subtrochanteric or diaphyseal regions of the femur. While some cases resemble fractures in rare genetic bone disorders, the exact cause r...

The genetic basis of severe COVID-19 has been thoroughly studied and many genetic risk factors shared between populations have been identified. However, reduced sample sizes from non-European groups have limited the discovery of population-specific common risk loci. In this second study nested in the SCOURGE consortium, we have conducted the larges...

Pre‐existing coronary artery disease (CAD), and thrombotic, inflammatory, or virus infectivity response phenomena have been associated with COVID‐19 disease severity. However, the association of candidate single nucleotide variants (SNVs) related to mechanisms of COVID‐19 complications has been seldom analysed. Our aim was to test and validate the...

Autism is more frequently diagnosed in males, with evidence suggesting that females are more likely to be misdiagnosed or underdiagnosed. Possibly, the male/female ratio imbalance relates to phenotypic and camouflaging differences between genders. Here, we performed a comprehensive approach to phenotypic and camouflaging research in autism addresse...

Aim Few genome‐wide association studies (GWAS) have been conducted for severe forms of periodontitis (stage III/IV grade C), and the number of known risk genes is scarce. To identify further genetic risk variants to improve the understanding of the disease aetiology, a GWAS meta‐analysis in cases with a diagnosis at ≤35 years of age was performed....

Purpose To determine whether genetic risk single nucleotide polymorphisms (SNPs) for age-related macular degeneration (AMD) influence short-term response to intravitreal ranibizumab treatment. Methods Forty-four treatment-naive AMD patients were included in a prospective observational study. They underwent three monthly injections of intravitreal...

Introduction: Small cell lung cancer (SCLC) comprises 10-15% of all lung cancer cases and is the most aggressive histological type. Survival is poor and the molecular landscape of this disease is extraordinarily complex. The objective of this paper was to perform a Genome-Wide Association Study (GWAS) of this disease using a case-control study spe...

Despite the high contagion and mortality rates that have accompanied the coronavirus disease-19 (COVID-19) pandemic, the clinical presentation of the syndrome varies greatly from one individual to another. Potential host factors that accompany greater risk from COVID-19 have been sought and schizophrenia (SCZ) patients seem to present more severe C...

Critical illness in COVID-19 is an extreme and clinically homogeneous disease phenotype that we have previously shown1 to be highly efficient for discovery of genetic associations2. Despite the advanced stage of illness at presentation, we have shown that host genetics in patients who are critically ill with COVID-19 can identify immunomodulatory t...

Background: The study of Obsessive-Compulsive Disorder (OCD) genomics has primarily been tackled by Genome-wide association studies (GWAS), which have encountered troubles in identifying replicable single nucleotide polymorphisms (SNPs). Endophenotypes have emerged as a promising avenue of study in trying to elucidate the genomic bases of complex...

Introduction: Genetic variants related to bone morphogenetic proteins (BMP2, BMP4, GREM1, SMAD7) signaling pathway have been associated with colorectal cancer, mainly in Caucasian populations. Objective: To describe the association of variants in members of the BMP signaling pathway in a Mexican population, characterized by its indigenous Americ...

Investigating the role of host genetic factors in COVID-19 severity and susceptibility can inform our understanding of the underlying biological mechanisms that influence adverse outcomes and drug development. Here we present a second updated genome-wide association study (GWAS) on COVID-19 severity and infection susceptibility to SARS-CoV-2 from t...

Introducción: Los amplia mayoría de los estudios de asociación de genoma completo (GWAS) se basan enpoblaciones europeas y si bien han logrado identificar regiones genómicas asociadas a diversaspatologías aún hay una gran porción de la variabilidad no explicada por esas regiones. Respecto alcáncer color-rectal (CRC) hay publicados GWAS en poblacion...

Aims: R-spondin 4 (RSPO4) is a suggestive risk gene of stage III-IV, grade C periodontitis and upregulated in gingiva of mice resistant to bacteria induced alveolar bone loss. We aimed to replicate the association, to identify and characterize the putative causal variant(s) and molecular effects and understand the downstream effects of RSPO4 upreg...

Background Sepsis is a severe systemic inflammatory response to infections that is accompanied by organ dysfunction and has a high mortality rate in adult intensive care units. Most genetic studies have identified gene variants associated with development and outcomes of sepsis focusing on biological candidates. We conducted the first genome-wide a...

Introducción: Variantes génicas relacionadas con la vía de señalización de las proteínas morfogenéticas óseas (BMP2, BMP4, GREM1, SMAD7) se han asociado a cáncer colorrectal, principalmente en poblaciones caucásicas. Objetivo: Describir la asociación de variantes en miembros de la vía BMP en población mexicana, caracterizada por su ancestría indoa...

ABSTACT Dysexecutive syndrome has been consistently reported in children and adolescents with autism spectrum disorders (ASD). Particularly, impairments have been documented in working memory, inhibition, and mental flexibility. However, the relationship between executive impairments and intellectual functioning is far from clear in this population...

Here we describe the results of a genome-wide study conducted in 11 939 COVID-19 positive cases with an extensive clinical information that were recruited from 34 hospitals across Spain (SCOURGE consortium). In sex-disaggregated genome-wide association studies for COVID-19 hospitalization, genome-wide significance (p < 5x10−8) was crossed for varia...

e15532 Background: Fluoropyrimidine-based treatments are still considered challenging due to the wide variability in efficacy and toxicity rates presented by patients. This variability can be explained, partially, by individual genetic differences that contribute significantly to the response of the drug, with 30% of patients experiencing severe to...

Background Sepsis is a severe systemic inflammatory response to infections that is accompanied by organ dysfunction and has a high mortality rate in adult intensive care units (ICUs). Most genetic studies have identified gene variants associated with development and outcomes of sepsis focusing on biological candidates. We conducted the first genome...

Neuronal differentiation is a complex process through which newborn neurons acquire the morphology of mature neurons and become excitable. We employed a combination of functional and transcriptomic approaches to deconvolute and identify key regulators of the differentiation process of a DRG neuron-derived cell line, and we focused our study on the...

In Brugada syndrome, even within the same family where all affected individuals share the same mutation, phenotypic variation is prominent, with variable penetrance and expressivity, presenting different degrees of involvement. It is difficult to establish a direct correlation between genotype and phenotype to predict prognosis in complications and...

The ongoing pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2, COVID-19) has an estimated overall case fatality ratio of 1.38% (pre-vaccination), being 53% higher in males and increasing exponentially with age. Among 9578 individuals diagnosed with COVID-19 in the SCOURGE study, we found 133 cases (1.42%) with detectabl...

PurposeGenetic variants in genes involved in the distribution, metabolism, accumulation or repair of lesions are likely to influence the response of drugs used in the treatment of Head and Neck Cancer (HNC). We examine the effect of 36 SNPs on clinical outcomes in patients with locally advanced HNC who were receiving platinum-based chemoradiotherap...

Current human populations are studied to elucidate their ancestry composition and to obtain reference values for an array of genetic markers for forensic practice. This study compared the 79 ancestry informative markers (AIMs) panel with the SNPforID 52plex set used in forensic identification, using samples belonging to Continental Caribbean popula...

Neuropathic pain is one of the foremost adverse effects that worsens quality of life for patients undergoing an antiretroviral treatment. Currently, there are no effective analgesics for relieving it; thus, there is an urgent need to develop novel treatments for neuropathic pain. Previously, we described and validated F11 cells as a model of DRG (d...

Severe periodontitis is prevalent in Down syndrome (DS). This study aimed to identify genetic variations associated with periodontitis in individuals with DS. The study group was distributed into DS patients with periodontitis (n = 50) and DS patients with healthy periodontium (n = 36). All samples were genotyped with the “Axiom Spanish Biobank” ar...

Background Lack of adherence in patients with inflammatory bowel disease (IBD) is a relevant problem in our clinical practice. Non-adherence to anti-TNF increases healthcare costs. The aim of this study was both to measure adherence and also to study the factors and consequences related to non-adherence in patients with IBD under maintenance treatm...

Purpose To describe the way patients die in a Spanish ICU, and how the modes of death have changed in the last 10 years. Materials and methods Retrospective observational study evaluating all patients who died in a Spanish tertiary ICU over a 10-year period. Modes of death were classified as death despite maximal support (D-MS), brain death (BD),...

Aim To identify loci associated with stages III/IV, grade C periodontitis (PIII/IV‐C) through a genome wide association study (GWAS). Materials And Methods 441 Caucasian Spanish PIII/IV‐C cases from the SEPA Network of Research Clinics and 1141 controls from the Banco Nacional de ADN were genotyped with “Axiom Spain Biobank Array”, which contains...

We aim to evaluate the role of single-nucleotide polymorphisms of the angiotensin-converting enzyme 2 in susceptibility to SARS-CoV-2 infection. We included 28 uninfected but highly exposed healthcare workers and 39 hospitalized patients with COVID-19. Thirty-five SNPs were rationally selected. Two variants were associated with increased risk of be...

Introduction The genetic admixture of the Brazilian population has considerable relevance to the implementation of the principles of pharmacogenomics (PGx), as it may compromise the extrapolation of data obtained in more homogeneous world populations. Purpose This study aims to investigate a panel of 117 polymorphisms in 35 pharmacogenes, which co...

SCA36 is an autosomal dominant spinocerebellar ataxia (SCA) affecting many families from Costa da Morte, a northwestern region of Spain. It is caused by an intronic GGCCTG repeat expansion in NOP56. In order to characterize the cognitive and affective manifestations of this cerebellar disease, a group of 30 SCA36 mutation carriers (11 preataxic and...

Background: Genome-wide association studies (GWAS) for colorectal cancer (CRC) have detected high-risk genetic variants associated with CRC in several ethnic groups, but Latin American communities are still underrepresented. The aim was to identify variants related to CRC in an admixed Latin American population. Methods: The study was performed in...

We studied the predictive value for response and toxicity of functional polymorphisms in genes involved in the oxaliplatin/fluorouracil pathway in colorectal cancer patients. One hundred and twenty-seven (127) patients were treated with curative intended surgery followed by adjuvant chemotherapy with FOLFOX (fluorouracil, leucovorin and oxaliplatin...

The multidimensional nature of obsessive-compulsive disorder (OCD) has been consistently reported. Clinical and biological characteristics have been associated with OCD dimensions in different ways. Studies suggest the existence of specific genetic bases for the different OCD dimensions. In this study, we analyze the genomic markers, genes, gene on...

Background: The severity of Obsessive-Compulsive Disorder (OCD) varies significantly among probands. No study has specifically investigated the genetic base of OCD severity. A previous study from our group found an OCD polygenic risk score to predict pre- and post-treatment severity. This study explores the genomic bases of OCD severity. Methods:...

This study analysed the Risk for Language Delay (RLD) in a sample of healthy preterm children and a full-term control group. We collected direct and indirect measures of language development from 10 to 60 months, and we examined the influence of biomedical, cognitive and environmental variables over the RLD at 22, 30, and 60 months. While at the ea...

Objectives: Frailty is a geriatric syndrome that identifies individuals at higher risk of disability, institutionalization, and death. We previously reported that frailty is related to oxidative stress and cognitive impairment-related biomarkers. The aim of this study was to determine whether frailty is associated with genetic variants. Design:...

Background Platinum‐based chemoradiotherapy (CRT) is the standard treatment for locally advanced head and neck squamous‐cell carcinomas (HNSCC), and most patients experience serious toxicities. The aim of this study was to investigate the association between candidate genes involved in radiation/platinum pathways and acute toxicity of CRT to determ...

This study analysed the Risk for Language Delay (RLD) in a sample of healthy preterm children and a full-term control group. We collected direct and indirect measures of language development from10 to 60 months, and we examined the influence of biomedical, cognitive and environmental variables over the RLD at 22, 30 and 60 months. While at the earl...

Background: Head and neck squamous cell carcinoma (HNSCC) is a global public health problem, which increases in prevalence every year. Evidence brings up that small populations of stem cells, the cancer stem cells (CSC), are responsible for tumour initiation, tumorigenesis, progression, and metastasis. These cells play a crucial role in cancer dev...

Introduction: The search for biomarkers that can lead to the early diagnosis and thus, early treatment of frailty, has become one of the main challenges facing the geriatric scientific community. The aim of the present study was to identify single nucleotide polymorphisms (SNPs) related to frailty. Material and methods: The study was conducted o...

The vocabulary size and composition of one group of full-term and three groups of low risk preterm children with different gestational ages (GA) were longitudinally compared at 10, 22 and 30 months of age. Expressive vocabulary development was assessed through the CDI. Cognitive development was also assessed at 22 months (Batelle Developmental Inve...

In this study, we intend to identify the evolutionary footprints of the South Iberian population focusing on the Berber and Arab influence, which has received little attention in the literature. Analysis of the Y-chromosome variation represents a convenient way to assess the genetic contribution of North African populations to the present-day South...

Intellectual disability (ID) is a complex and phenotypically heterogeneous neurodevelopmental disorder characterized by significant deficits in cognitive and adaptive skills, debuting during the developmental period. In the last decade, microarray-based copy number variation (CNV) analysis has been proved as a strategy particularly useful in the di...

Este trabajo se propone analizar la evolución de la incidencia del riesgo/retraso del lenguaje y sus posibles factores de vulnerabilidad en un grupo de niños prematuros de bajo riesgo (EG media de 32,6 semanas y sin secuelas neurológicas evidentes). Para ello, se ha estudiado una muestra inicial de 150 niños prematuros (PR), y 49 niños nacidos a té...

Este trabajo se propone analizar la evolución de la incidencia del riesgo/retraso del lenguaje y sus posibles factores de vulnerabilidad en un grupo de niños prematuros de bajo riesgo (EG media de 32,6 semanas y sin secuelas neurológicas evidentes). Para ello, se ha estudiado una muestra inicial de 150 niños prematuros (PR), y 49 niños nacidos a té...

Human mitochondrial DNA (mtDNA) shows extensive within-population sequence variability. Many studies suggest that mtDNA variants may be associated with ageing or diseases, although mechanistic evidence at the molecular level is lacking. Mitochondrial replacement has the potential to prevent transmission of disease-causing oocyte mtDNA. However, ext...

Genetic factors have a significant impact on the PK variability of EFV, much higher than other non-genetic factors, such as demography. In this work we have performed a comprehensive PG analysis of genes encoding the major metabolizing enzymes and transporters of EFV, establishing a clear relationship between the PK parameters and genetic factors,...

Introduction: Longevity is determined by genetic and external factors, such as nutritional, environmental, social, etc. Nevertheless, when living conditions are optimal, longevity is determined by genetic variations between individuals. In a same population, with relative genotypic homogeneity, subtle changes in the DNA sequence affecting a single...

Background: The response to thiopurine treatment in inflammatory bowel disease patients differs greatly among individuals and nearly 50% of patients experience no benefit. Several factors have been implicated in determining this response, including individual genetic variation. Methods: Aiming to identify genes involved in the response to thiopurin...

DNA profiling is a key tool for forensic analysis; however, current methods identify a suspect either by direct comparison or from DNA database searches. In cases with unidentified suspects, prediction of visible physical traits e.g. pigmentation or hair distribution of the DNA donors can provide important probative information. This study aimed to...

Atraumatic subtrochanteric and diaphyseal (atypical) femoral fractures are a rare, but important adverse event in patients treated with potent anti-resortive agents. The mechanisms involved are unknown and particularly the association with genetic variants has not been explored. The aim of the study was to identify rare genetic variants that could...

Allelic imbalance of thymidylate synthase (TYMS) is attributed to polymorphisms in the 5′- and 3′-untranslated region (UTR). These polymorphisms have been related to the risk of suffering different cancers, for example leukemia, breast or gastric cancer, and response to different drugs, among which are methotrexate glutamates, stavudine, and specif...

O emprego de programas de imputación xenética forma parte da práctica habitual en estudos de asociación xenética e meta-análises, xa que o panel de SNPs xenotipados varía en función da plataforma comercial utilizada en cada caso. Aínda que estes programas achegan o xenotipo individual para o SNP de interese, o dato necesario para as análises poster...

Thyroid cancer is the most heritable cancer of all those not displaying typical Mendelian inheritance. However, most of the genetic factors that would explain the high heritability remain unknown. Our aim was to identify additional common genetic variants associated with susceptibility to this disease. In order to do so, we performed a genome-wide...

There is growing interest in skin colour prediction in the forensic field. However, a lack of consensus approaches for recording skin colour phenotype plus the complicating factors of epistatic effects, environmental influences such as exposure to the sun and unidentified genetic variants, present difficulties for the development of a forensic skin...

Aims: We present a genetic association study in 106 European HIV-infected individuals aimed at identifying and confirming polymorphisms that have a significant influence on toxicity derived from treatment with lopinavir/ritonavir (LPV/r). Patients & methods: Genotyping was performed by matrix-assisted laser desorption/ionization-time of flight a...

A esclerose múltiple (EM) é unha enfermidade complexa que presenta unha prevalencia moi variable xeograficamente. En Galicia acada unha prevalencia de 79 casos por cada 100.000 habitantes, a taxa máis alta das zonas xeográficas de España estudadas ata o momento. Aínda que cada vez se coñece máis da súa base xenética, parece que os factores ambienta...

Despite the known benefits and the experienced use of lopinavir/ritonavir (LPV/r) in the management of HIV infection, important interindividual variability in the pharmacokinetics (PKs) and the response to treatment with standard doses of this drug has been observed. Host genetic factors have been recently suggested as being responsible for part of...

Aim: This article evaluates which genetic factors are involved in CNS toxicity related to long-term treatment with efavirenz (EFV) standard doses and their relationship with plasma concentrations. Patients & methods: A total of 119 HIV-positive patients, in which 1350 EFV plasma concentrations, 68 SNPs and 14 EFV-related adverse effects (AEs) we...

The textbook description of mitochondrial respiratory complexes (RCs) views them as free-moving entities linked by the mobile carriers coenzyme Q (CoQ) and cytochrome c (cyt c). This model (known as the fluid model) is challenged by the proposal that all RCs except complex II can associate in supercomplexes (SCs). The proposed SCs are the respiraso...

Background: The toxicity related to thiopurine drug therapy for inflammatory bowel disease (IBD) varies widely among patients. Almost 15-30% of patients with IBD develop side effects during treatment, often bone marrow suppression. Several factors have been implicated in determining this toxicity, mainly individual genetic variation related to for...

Objective: Determine the prevalence and compare some genetic markers involved in addictive behavior in a group of addicts to derivative of coca (cocaine/crack) or heroin and a control group of non-addicted people matched for gender, age and ethnicity. Methods: A 120 addicts and 120 non-addicts Colombian male were surveyed and genotyped for 18 pol...

Objective: Determine the prevalence and compare some genetic markers involved in addictive behavior in a group of addicts to derivative of coca (cocaine/crack) or heroin and a control group of non-addicted people matched for gender, age and ethnicity. Methods: A 120 addicts and 120 non-addicts Colombian male were surveyed and genotyped for 18 polym...

Objective: Determine the prevalence and compare some genetic markers involved in addictive behavior in a group of addicts to derivative of coca (cocaine/crack) or heroin and a control group of non-addicted people matched for gender, age and ethnicity. Methods: A 120 addicts and 120 non-addicts Colombian male were surveyed and genotyped for 18 polym...

Algunas enfermedades complejas muestran patrones geográficos de distribución difícilmente explicables. La integración de factores genéticos y ambientales mediante sistemas de información geográfica y análisis estadísticos que contemplen la dimensión espacio-temporal de los datos permitiría discernir las complejas interacciones gen-ambiente que pued...

Williams syndrome is characterized by impairments in executive functions (EFs). However, it remains unknown how distinct types of EFs relate to intelligence in this syndrome. The present study analyzed performance on working memory, inhibiting and shifting, and its links to IQ in a sample of 17 individuals with WS, and compared them with a group of...

In forensic analysis predictive tests for external visible characteristics (or EVCs), including inference of iris color, represent a potentially useful tool to guide criminal investigations. Two recent studies, both focused on forensic testing, have analyzed single nucleotide polymorphism (SNP) genotypes underlying common eye color variation (Menge...

Smith-Magenis Syndrome (SMS) is a genetic neurodevelopmental disorder caused by a microdeletion on chromosome 17p11.2. This syndrome is characterized by a distinctive profile of physical, medical and neuropsychological characteristics. The latter include general mental disability, with the majority of individuals falling within the mild to moderate...

The genetically variable CYP450 isozymes are responsible for the metabolism of up to 80% of commonly used drugs, many of which are detected in cases of unexpected or suspicious death in Australia. The aim of this study was to examine the genetic profiles of individuals in a cohort of Australian deceased individuals dying of drug toxicity (219), nat...