Luba Milena Pardo

• MD, PhD
• Assistant Professor at Erasmus Medical Center Rotterdam

We aimed to assess the impact of splicing variants reported in our laboratory to gain insight into their clinical relevance. A total of 108 consecutive individuals, for whom 113 splicing variants had been reported, were selected for RNA-sequencing (RNA-seq), considering the gene expression in blood. A protocol was developed to perform RNA extractio...

Background Environmental factors play a role in the pathogenesis of complex traits including atopic eczema (AE) and a greater understanding of gene-environment interactions (G*E) is needed to define pathomechanisms for disease prevention. We analysed data from 16 European studies to test for interaction between the 24 most significant AE-associated...

Background: Hereditary transthyretin-related amyloidosis is a clinically heterogeneous autosomal dominant disease caused by pathogenic variants in the TTR gene (hATTR amyloidosis). Objective: The current study describes the demographic, clinical, and genetic characteristics of patients with suspected hATTR amyloidosis. Methods: This study is part o...

Background Perceived age (PA) has been associated with mortality, genetic variants linked to ageing and several age‐related morbidities. However, estimating PA in large datasets is laborious and costly to generate, limiting its practical applicability. Objectives To determine if estimating PA using deep learning‐based algorithms results in the sam...

Background Itch, common in dermatological conditions, is often accompanied by psychological distress and reduced quality of life. However, research on the prevalence and associated factors of itch with skin conditions in general populations is limited. Objectives This cross-sectional study aimed to determine the lifetime prevalence of itch with sk...

Background Efficient identification of individuals at high risk of skin cancer is crucial for implementing personalized screening strategies and subsequent care. While Artificial Intelligence holds promising potential for predictive analysis using image data, its application for skin cancer risk prediction utilizing facial images remains unexplored...

The Rotterdam Study is a population-based cohort study, started in 1990 in the district of Ommoord in the city of Rotterdam, the Netherlands, with the aim to describe the prevalence and incidence, unravel the etiology, and identify targets for prediction, prevention or intervention of multifactorial diseases in mid-life and elderly. The study curre...

Background/Purpose Cutaneous squamous cell carcinoma (cSCC) is one of the most common malignancies worldwide. While several environmental risk factors for cSCC are well established, there is conflicting evidence on cigarette smoking (and its potential causal effect) and cSCC risk. Furthermore, it is unclear if these potential associations represent...

Syndromic constitutive thrombocytopenia encompasses a heterogeneous group of disorders characterised by quantitative and qualitative defects of platelets while featuring other malformations. Recently, heterozygous, de novo variants in RAP1B were reported in three cases of syndromic thrombocytopenia. Here, we report two additional, unrelated individ...

Purpose With this study, we aimed to explore the gene-disease relationship (GDR) evidence for 109 gene-disease pairs and the significance of a large Biodatabank for this classification. Methods The Clinical Genome Resource (ClinGen) Clinical Validity Framework for evaluation of GDR was applied. Most of the assessed genes were without a phenotype e...

Niemann-Pick type C1 disease (NPC1 [OMIM 257220]) is a rare and severe autosomal recessive disorder, characterized by a multitude of neurovisceral clinical manifestations and a fatal outcome with no effective treatment to date. Aiming to gain insights into the genetic aspects of the disease, clinical, genetic, and biomarker PPCS data from 602 patie...

Limited population-based studies are available to analyze the prevalence, risk factors, and longitudinal outlook of actinic keratoses (AK). These aforementioned features were assessed using Rotterdam Study participants aged 40 and older who underwent a full-body skin examination (FBSE) by a dermatology trained physician. Odds ratios (ORs) with 95%...

Background Outdoor work is associated with high and chronic exposure to solar ultraviolet radiation which might lead to an increased risk of developing skin (pre)malignancies. Prevalence of actinic keratosis (AK), basal cell carcinoma (BCC), cutaneous squamous cell carcinoma (cSCC) and cutaneous melanoma (cM) in Dutch outdoor workers (OW) has not p...

Background Looking older for one’s chronological age is associated with a higher mortality rate. Yet it remains unclear how perceived facial age relates to morbidity and the degree to which facial ageing reflects systemic ageing of the human body. Objectives To investigate the association between ΔPA and age-related morbidities of different organ...

Probiotics and synbiotics are used to treat chronic illnesses due to their roles in immune system modulation and anti-inflammatory response. They have been shown to reduce inflammation in a number of immune-related disorders, including systemic lupus erythematosus (SLE), human immunodeficiency virus (HIV), and chronic inflammatory skin conditions s...

Background: Interactions between the skin barrier, immune system, and microbiome underlie the development of atopic dermatitis (AD). Objective: To investigate the skin and nasal microbiome in relation to filaggrin gene (FLG) mutations. Methods: A cross-sectional study including 77 children with difficult-to-treat AD. The entire encoding region...

Atopic dermatitis (AD) is a common inflammatory skin disease among children with increasing prevalence in the past decades. The strongest and most widely replicated genetic risk factor for AD is a null mutation in the filaggrin gene (FLG) located on chromosome 1q21. FLG encodes the protein filaggrin, which is involved in the formation and homeostas...

Ultraviolet (UV) light and incompletely understood genetic and epigenetic variations determine skin color. Here we describe an UV- and microphthalmia-associated transcription factor (MITF)-independent mechanism of skin pigmentation. Targeting the mitochondrial redox-regulating enzyme nicotinamide nucleotide transhydrogenase (NNT) resulted in cellul...

The Rotterdam Study is an ongoing prospective, population-based cohort study that started in 1989 in the city of Rotterdam, the Netherlands. The study aims to unravel etiology, preclinical course, natural history and potential targets for intervention for chronic diseases in mid-life and late-life. It focuses on cardiovascular, endocrine, hepatic,...

The Rotterdam Study is an ongoing prospective, population-based cohort study that started in 1989 in the city of Rotterdam, the Netherlands. The study aims to unravel etiology, preclinical course, natural history and potential targets for intervention for chronic diseases in mid-life and late-life. It focuses on cardiovascular, endocrine, hepatic,...

Background Seborrheic dermatitis (SD) is a chronic inflammatory skin disease with a multifactorial aetiology. Malassezia yeasts have been associated with the disease but the role of bacterial composition in SD has not been thoroughly investigated. Objectives To profile the bacterial microbiome of SD patients and compare this with the microbiome of...

Background: Staphylococcus aureus colonization is associated with disease severity in patients with atopic dermatitis (AD). Objective: To investigate temporal variation in S. aureus protein A gene (spa)-types isolated from the nose and lesional skin and the correlation of spa-types with disease severity. Results: This study included 96 adult A...

Background Infants with less diverse gut microbiota seem to have higher risks of atopic diseases in early life, but any associations at school age are unclear. Objective To examine the associations of diversity, relative abundance and functional pathways of stool microbiota with atopic diseases in school-aged children. Methods We performed a cros...

Background Mutations in the filaggrin gene (FLG) affect epidermal barrier function and increase the risk of atopic dermatitis (AD). We hypothesized that FLG mutations affect immune cell composition in a general pediatric population. Therefore, we investigated whether school‐aged children with and without FLG mutations have differences in T‐ and B‐c...

Background An association has been reported between early life Staphylococcus aureus nasal carriage and higher risk of childhood eczema, but it is unclear whether this relationship is causal and associations with other bacterial species are unclear. Objective To examine the associations of early life nasal and nasopharyngeal bacterial carriage wit...

Background: Mutations in the filaggrin gene (FLG) affect epidermal barrier function and increase the risk of atopic dermatitis (AD). We hypothesized that FLG mutations affect immune cell composition in a general pediatric population. Therefore, we investigated if school-aged children with and without FLG mutations have differences in immune cell nu...

Background The severity of facial telangiectasia or red veins is associated with many lifestyle factors. However, the genetic predisposition remains unclear. Objectives We performed a genome‐wide association study (GWAS) on facial telangiectasia in the Rotterdam Study (RS) and tested for replication in two independent cohorts. Additionally, a cand...

Facial ageing is characterised by several skin changes, but it is not currently clear how these changes are related to each other, and how these are linked to the different types of facial ageing. This study, involving investigators from the Netherlands, China and the U.K., was designed to identify which facial changes are best associated with diff...

Cutaneous squamous cell carcinoma (SCC) is one of the most common cancers in the United States. Previous genome-wide association studies (GWAS) have identified 14 single nucleotide polymorphisms (SNPs) associated with cutaneous SCC. Here, we report the largest cutaneous SCC meta-analysis to date, representing six international cohorts and totaling...

Background: Patients with actinic keratosis (AK) are at increased risk for developing keratinocyte carcinoma (KC) but predictive factors and their risk rates are unknown. Objectives: To develop and internally validate a prediction model to calculate the absolute risk of a first KC in AK patients. Methods: The risk prediction model was based on...

Background Telangiectasia or red veins are one of the prominent features of facial skin ageing. To date, there are few studies investigating the determinants of telangiectasia. Objectives We investigated lifestyle and physiological factors associated with facial telangiectasia in a large prospective Dutch cohort study. Methods Telangiectasia was...

Recent reports have suggested a reproducible association between the rs11121615 SNP, located within an intron of the castor zinc finger 1 (CASZ1) gene, and varicose veins. This study aimed to determine if this variant is also differentially associated with the various clinical classifications of chronic venous disease (CVD). The rs11121615 SNP was...

Background: The skin microbiome, characterized by an overgrowth of Staphylococcus aureus, plays an important role in the pathogenesis of atopic dermatitis (AD). Multidisciplinary treatment in alpine climate is known for its positive effect on disease severity in children with AD and can result in a different immune response compared with moderate...

Background: The underlying phenotypic correlations between wrinkles, pigmented spots, telangiectasia and other related facial ageing sub-phenotypes are not well understood. Objectives: To analyse the underlying phenotypic correlation structure between seven features for facial ageing: global wrinkling, Perceived Age (PA), Griffiths photo-damage...

Background Alterations of the skin microbiome have been associated with atopic dermatitis (AD) and its severity. The nasal microbiome in relation to AD severity is less well studied. Objective We aimed to characterize the nasal and skin microbiome in children with AD in relation to disease severity. Additionally, we explored differences and correl...

The authors regret that Luba M. Pardo was omitted in error from the author list of the original version of this Data Descriptor. This omission has now been corrected in the HTML and PDF versions. The authors also regret that Anemieke Rozemuller was omitted in error from the Acknowledgements of the original version of this Data Descriptor. This omis...

Background Several observational studies have suggested differences in the risk factor profile between patients with superficial basal cell carcinomas (BCCs) and non‐superficial BCCs. Objective To test the reproducibility of previous study findings and to find new genetic and non‐genetic predictors for patients with a superficial first BCC. Metho...

Background: Determinants and the extent of dry skin in healthy middle-aged and elderly populations have not been well established. Objective: We aimed to identify the prevalence and determinants for generalized dry skin (GDS) and localized dry skin (LDS) within a large prospective population-based cohort of middle-aged and elderly individuals of...

Background: Due to the increasing incidence of basal cell carcinoma (BCC) and rising health care costs, health care insurance companies seek ways to shift skin surgery for BCC from secondary to primary care. Objectives: To study the differences in complete excision of BCC by general practitioners (GPs), dermatologists, and plastic surgeons. Met...

Current treatments for seborrheic dermatitis only provide a temporary relief. Therefore, identifying modifiable lifestyle factors may help to reduce disease burden. The objective of this study was to determine whether specific dietary patterns or total antioxidant capacity are associated with seborrheic dermatitis. Participants of the Rotterdam Stu...

本研究由来自荷兰和瑞士的团队开展,旨在探索异位性湿疹患者产生被称为IgG的抗体类型与对抗金黄色葡萄球菌这类细菌的组成部分的关系。金黄色葡萄球菌常见于患有异位性湿疹的儿童和成人皮肤中,主要是通过刺激免疫系统或引起对细菌本身的过敏反应导致病情恶化。在本研究中,研究人员观察了异位性湿疹患者存在对抗不同细菌组成部分的IgG类抗体的情况,然后将其与疾病严重程度进行了对比。他们发现,抗体能对抗细菌产物(有时称为毒力因子),而细菌产物涉及到减少正常免疫反应,与疾病加重有关。在本研究中,破坏人类白细胞的某种蛋白质就是降低免疫力的细菌产物的一个示例。这表明这些降低免疫力的组成部分也可能通过延长有机体在皮肤表面的寿命成为加重湿疹的因素,这也从另一个角度解释了为何应在患有湿疹的皮肤上减少或全部去除金黄色葡萄球菌这...

This study, carried out by a group from the Netherlands and Switzerland, explored the relationship between production of the antibody type known as IgG against components of the bacteria Staphylococcus aureus by patients with atopic eczema. This bacterium is frequently found on the skin of children and adults with atopic eczema and has been associa...

Background: Most pathogenic mutations in the BRCA2 gene carry a high risk of hereditary breast and ovarian cancer (HBOC). However, a stop-gain mutation, K3326* (rs11571833), confers risk of lung cancer and cancers of the upper-aero-digestive tract but only a modest risk of breast or ovarian cancer. The Icelandic population provides an opportunity...

脂溢性皮炎是一种常见的皮肤病,见于头皮、面部及胸部,主要表现为炎症和脂性鳞屑。虽然尚不清楚脂溢性皮炎的病因,但研究者认为马拉色氏酵母菌的过度生长是脂溢性皮炎的部分原因。若干其他因素也与此类疾病有关;年龄、性别、肥胖、肤色、压力、沮丧、教育程度、高血压、气候、皮肤干燥、饮酒以及吸烟等因素都与脂溢性皮炎有关,但相关性证据通常并无定论。该研究旨在确定与脂溢性皮炎有关的生活方式及生理因素。该研究中的数据来自针对荷兰中老年人群开展的鹿特丹研究,旨在研究这些之前报告的因素。研究依据在于,了解决定因素可以在脂溢性皮炎的病理生理学方面提供新的见解,以便采取预防策略和/或新的治疗方案。在鹿特丹研究中,5,498 位参与者进行了全身皮肤检查,其中 788 位罹患脂溢性皮炎。作者发现,男性、肤色浅、冬季以及全身干...

Seborrheic dermatitis is a common skin disorder occurring on the scalp, face and chest and is characterized by inflammation and a greasy scaling. It is not clear what causes seborrheic dermatitis, but it is thought that overgrowth of Malassezia yeasts contributes to developing seborrheic dermatitis. Several other factors have been associated with t...

Seborrheic dermatitis is a chronic inflammatory skin disease with a complex etiology. The genetic predisposition for seborrheic dermatitis has not been studied, resulting in the absence of candidate genes involved in the pathogenesis of this condition. However, seborrheic dermatitis shares several clinical features with other chronic inflammatory s...

Background: An altered immune response against Staphylococcus (S.) aureus might contribute to inflammation and barrier damage in atopic dermatitis (AD). Objectives: We profiled IgG antibodies against 55 S. aureus antigens in sera of children with mild to severe AD using a Luminex assay. Additionally, we evaluated the association between IgG leve...

Background: Melanoma is rare in the first two decades of life. Trends in incidence differ across countries. Objective: To describe incidence and relative survival of children and adolescents with melanoma in the Netherlands for children (0 through 11 years) and adolescents (12 through 19 years) separately. We hypothesized that adolescent melanom...

Background Atopic dermatitis (AD) is associated with reduced skin microbial diversity and overgrowth of Staphylococcus (S.) aureus. However, the importance of S. aureus colonisation in the complex pathogenesis remains unclear and studies on the effect of anti-staphylococcal therapy in non-infected AD show contradictory results. Long-term interventi...

Background: Seborrheic dermatitis is a chronic relapsing inflammatory skin disease with unclear pathophysiological mechanisms. Objective: To establish which lifestyle and physiological determinants are associated with seborrheic dermatitis. Methods: Seborrheic dermatitis was diagnosed by a trained physician during a full body skin examination...

Data from in-vitro experiments suggest vitamin D reduces the rate of skin aging whereas population studies suggest the opposite, most likely due to confounding by UV-exposure. We investigated whether there are causal associations between 25-hydroxyvitamin D concentrations and features of skin aging in a bidirectional Mendelian Randomization Study....

Facial wrinkling is one of the most notable signs of skin aging. Men and women show different wrinkling patterns yet the lifestyle and physiological factors underlying these sex-specific patterns are relatively unknown. Here, we investigated sex-specific determinants for facial wrinkles. Wrinkle area was quantified digitally using facial photograph...

The prevalence of several skin diseases increases with age, in part due to age-related physio-pathological alterations.1 The global burden of disease project (GBD) 2,3 presented a comprehensive overview of the burden due to skin diseases across different age groups. However, the point prevalences of many common skin diseases, especially in elderly...

There is strong evidence for a role of environmental risk factors involved in susceptibility to develop multiple keratinocyte cancers (mKCs), but whether genes are also involved in mKCs susceptibility has not been thoroughly investigated. We investigated whether single nucleotide polymorphisms (SNPs) are associated with susceptibility for mKCs. A g...

Power calculation of the study design. The power of the study was calculated using the program CaTS with sample size, p-value (1x10-6) and a disease prevalence of 10% as fixed parameters. An 80% power was expected for markers with MAF>25% and Odd ratios of >1.3 (TIF)

Summary statistics of the most significant statistical associations between SNPs and mKCs in the discovery sample. The table presents the summary statistics of the eight regions with the most significant SNP associations and mKCs in the discovery sample. (XLSX)

Quality control of the genotyping for the NHSI-II-HPFS, FHS and RS GWAS and supplementary references. (DOCX)

Summary statistics of the most significant statistical associations for other SNPs and mKCs in the joint meta-analysis phase. The table presents the summary statistics of the most significant associations in the combined analysis (meta-analysis). (XLSX)

Regional plot of the most significant associations between SNPs in the short arm of chromosome 9 and mKCs. The plots represents the LD patterns of the most significant SNP in the study (rs468390) and nearby SNPs from this study (+/- 500 kb). Pairwise r2 is represented in colours. The log p-values of the associations of the rs468390 SNP and markers...

Summary statistics of the most significant statistical associations from the discovery phase in the replication and joint meta-analysis phase. The table presents the summary statistics of the most significant associations that were followed in the replication sample and also in the combined analysis (meta-analysis). (XLSX)

In the Netherlands the incidence of melanoma has been increasing whilst melanoma survival has improved significantly in the last 20 years(1) . As a result, there is an increasing number of melanoma survivors, who are at increased risk of developing new melanomas(2) . There is limited and conflicting literature concerning the survival of patients wi...

Looking young for one's age has been a desire since time immemorial. This desire is attributable to the belief that appearance reflects health and fecundity. Indeed, perceived age predicts survival [1] and associates with molecular markers of aging such as telomere length [2]. Understanding the underlying molecular biology of perceived age is vital...

Background: Aneurysms affecting the aorta are a common condition associated with high mortality as a result of aortic dissection or rupture. Investigations of the pathogenic mechanisms involved in syndromic types of thoracic aortic aneurysms, such as Marfan and Loeys-Dietz syndromes, have revealed an important contribution of disturbed transformin...

Actinic keratosis (AK) is a pre-malignant skin disease, highly prevalent in elderly Europeans. This study investigates genetic susceptibility to AK with a genome-wide association study (GWAS). A full body skin examination was performed in 3194 elderly individuals from the Rotterdam Study (RS) of exclusive north-western European origin (aged 51-99 y...

To characterize the promoterome of caudate and putamen regions (striatum), frontal and temporal cortices, and hippocampi from aged human brains, we used high-throughput cap analysis of gene expression to profile the transcription start sites and to quantify the differences in gene expression across the 5 brain regions. We also analyzed the extent t...

Genomic rearrangements involving AUTS2 (7q11.22) are associated with autism and intellectual disability (ID), although evidence for causality is limited. By combining the results of diagnostic testing of 49,684 individuals, we identified 24 microdeletions that affect at least one exon of AUTS2, as well as one translocation and one inversion each wi...

Next generation sequencing is quickly replacing microarrays as a technique to probe different molecular levels of the cell, such as DNA or RNA. The technology provides higher resolution, while reducing bias. RNA sequencing results in counts of RNA strands. This type of data imposes new statistical challenges. We present a novel, generic approach to...

Sardinia has been used for genetic studies because of its historical isolation, genetic homogeneity and increased prevalence of certain rare diseases. Controversy remains concerning the genetic substructure and the extent of genetic homogeneity, which has implications for the design of genome-wide association studies (GWAS). We revisited this issue...

The genome sequencing projects completed in recent years revealed that the number of protein-coding genes does not change appreciably with increasing complexity of the organisms, and it is now generally accepted that this divergence is largely due to variation at the regulatory level. Mechanisms such as alternative splicing, alternative promoters a...

The HapMap project has facilitated the selection of tagging single nucleotide polymorphisms (tagSNPs) for genome-wide association studies (GWAS) under the assumption that linkage disequilibrium (LD) in the HapMap populations is similar to the populations under investigation. Earlier reports support this assumption, although in most of these studies...

The E4 allele of the apolipoprotein E gene (APOE) is a well-established determinant of Alzheimer's disease but its relation to cognitive function is much less understood. We studied the age-specific effects of the APOE*E4 allele on cognitive function and cardiovascular risk factors in 2208 related individuals. APOE*E4 allele was significantly assoc...

Despite well-known sex differences in body composition it is not known whether sex-specific genetic or environmental effects contribute to these differences. We assessed body composition in 2,506 individuals, from a young Dutch genetic isolate participating in the Erasmus Rucphen Family study, by dual-energy X-ray absorptiometry and anthropometry....

Comparative genomics offers a novel approach to unravel the genetic basis of complex traits. We performed a two stage analysis where genes ascertained for enhanced protein evolution in primates are subsequently searched for the presence of non-synonymous coding SNPs in the current human population at amino acid sites that differ between humans and...

Ubiquilin 1 (UBQLN1) is involved in the ubiquitination machinery, which has been implicated in Alzheimer's disease (AD) as well as Parkinson's disease (PD). A polymorphism in the gene encoding for UBQLN1 has been previously associated with a higher risk of AD. We studied the role of the SNP rs12344615 on the UBQLN 1 gene in AD, PD and cognitive fun...

The genetic etiology of primary open-angle glaucoma (POAG) is still largely unknown, because of its complexity and disparities in its classification. This study was undertaken to determine the genetic contribution to various early, continuous markers of POAG by assessing the heritability of intraocular pressure (IOP), retinal nerve fiber layer (RNF...

Multiple sclerosis (MS) is a complex disease with a substantial, yet poorly identified, genetic influence. We estimated the pattern of familial aggregation of MS in a recent genetically isolated population in the Netherlands. Forty-eight MS patients were identified. Their relationship was evaluated by tracing extended pedigrees, making use of munic...