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Marios Georgakis

Marios Georgakis
Ludwig-Maximilians-University of Munich & Massachusetts General Hospital · Institute for Stroke and Dementia Research (ISD) & Center for Genomic Medicine (CGM)

MD, PhD

About

121
Publications
11,461
Reads
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1,785
Citations
Additional affiliations
September 2017 - present
Ludwig-Maximilians-University of Munich
Position
  • PhD Student
September 2016 - September 2017
Biomedical Research Foundation of the Academy of Athens
Position
  • Master's Student
September 2015 - September 2017
Uppsala University
Position
  • Research Assistant
Education
September 2017 - April 2020
Ludwig-Maximilians-University of Munich
Field of study
  • Neurosciences (Graduate School of Systemic Neurosciences)
September 2015 - September 2017
Medical School, National and Kapodistrian University of Athens, Greece
Field of study
  • Molecular and Applied Physiology (Neuroscience and Neurophysiology)
September 2009 - August 2015
Medical School, National and Kapodistrian University of Athens
Field of study
  • Medicine

Publications

Publications (121)
Article
Statins lower low-density lipoprotein (LDL) cholesterol and are widely used for the prevention of atherosclerotic cardiovascular disease. Whether statin-induced LDL reduction increases risk of intracerebral hemorrhage (ICH) has been debated for almost two decades. Here, we explored whether genetically predicted on-statin LDL response is associated...
Preprint
Background Intracerebral hemorrhage (ICH), the most fatal form of stroke, has an estimated heritability of 29%. Applying a meta-scoring approach, we developed a genomic risk score for ICH and determined its predictive power in comparison to standard clinical risk factors. Methods Using a meta-analytic approach, we combined genome-wide association...
Article
Background and Purpose Vascular risk factors may influence cognitive function and thus represent possible targets for preventive approaches against dementia. Yet it remains unknown, if they associate with cognition independently of the individual genetic risk for dementia. Methods In a population-based study of 1,172 community-dwelling individuals...
Article
Background and aims: Increased risk of stroke, particularly large artery stroke (LAS), has been observed in patients with COVID-19. The biological processes underlying the observed higher risk are still unknown. We explored the association between stroke subtypes and COVID-19 susceptibility to understand whether biological mechanisms specific to SA...
Article
Background The CCL2 (CC-chemokine ligand 2)/CCR2 (CC-chemokine receptor 2) axis governs monocyte recruitment to atherosclerotic lesions. Genetic and epidemiological studies show strong associations of CCL2 levels with atherosclerotic disease. Still, experimental studies testing pharmacological inhibition of CCL2 or CCR2 in atheroprone mice apply wi...
Preprint
Statins lower low-density lipoprotein (LDL) cholesterol and are widely used for the prevention of atherosclerotic cardiovascular disease. Whether statin-induced LDL reduction increases risk of intracerebral hemorrhage (ICH) has been debated for almost two decades. Here, we explored whether genetically predicted LDL response to statins is associated...
Article
Decades of research have established atherosclerosis as an inflammatory disease. Only recently though, clinical trials provided proof-of-concept evidence for the efficacy of anti-inflammatory strategies with respect to cardiovascular events, thus offering a new paradigm for lowering residual vascular risk. Efforts to target the inflammasome-interle...
Article
Objective: Ischemic stroke etiology remains undetermined in 30% of cases. We explored the genetic architecture of stroke classified as undetermined to test if mechanisms and risk factors underlying large-artery atherosclerotic (LAAS), cardioembolic (CES), and small-vessel stroke (SVS) contribute to its pathogenesis. Methods: We analyzed genome-w...
Article
Background: Evidence suggests marginal superiority of static aortic systolic blood pressure (aSBP) compared with brachial SBP regarding the association with organ damage and prognosis of cardiovascular disease. The noninvasive 24-hour aSBP assessment is feasible and associates better with presence of left ventricular hypertrophy compared with 24-h...
Article
Full-text available
Background: Frailty is a complex geriatric syndrome arising from a combination of genetic and environmental factors and is associated with adverse health outcomes and mortality. A recent study reported an association between variants of the 9p21-23 locus, associated with a number of age-related disorders, including Alzheimer's disease (AD), and fr...
Article
Background and Objectives Human genetic studies support a key role of interleukin-6 (IL-6) in the pathogenesis of ischemic stroke. Still, there are only limited data from observational studies exploring circulating IL-6 levels as a risk factor for ischemic stroke. Here, we set out to perform a systematic review and meta-analysis of aggregate data o...
Article
Background Although trials suggest that anti‐inflammatory approaches targeting interleukin (IL)‐6 signaling can reduce cardiovascular risk, it remains unknown whether targeting IL‐6 signaling could reduce risk additively to low‐density lipoprotein cholesterol (LDL‐C) lowering. Here, we assess interactions in associations of genetic downregulation o...
Article
Background and purpose: Observational studies suggest an association of stroke with cardiac traits beyond atrial fibrillation, the leading source of cardioembolism. However, controversy remains regarding a causal role of these traits in stroke pathogenesis. Here, we leveraged genetic data to systematically assess associations between cardiac trait...
Preprint
Full-text available
Previous genome-wide association studies (GWAS) of stroke, the second leading cause of death, have been conducted in populations of predominantly European ancestry.1,2 We undertook cross-ancestry GWAS meta-analyses of stroke and its subtypes in 110,182 stroke patients (33% non-European) and 1,503,898 control individuals of five ancestries from popu...
Article
Background: Higher segregation of functional networks in the brain has been associated with better cognitive abilities in aging (Chan, PNAS, 2014) and higher cognitive resilience against Alzheimer's disease (Ewers, Brain, in press). Here, we elucidated for the first time the genetic and environmental (i.e. cardiovascular) determinants of system se...
Article
Objective- Cardiovascular risk factors have been implicated in the etiology of Cerebral Small Vessel Disease (CSVD), however whether the associations are causal remains unclear in part due to the susceptibility of observational studies to reverse causation and confounding. Here we use Mendelian randomization (MR) to determine which cardiovascular r...
Article
Full-text available
The kidney and the brain, as high-flow end organs relying on autoregulatory mechanisms, have unique anatomic and physiological hemodynamic properties. Similarly, the two organs share a common pattern of microvascular dysfunction as a result of aging and exposure to vascular risk factors (e.g., hypertension, diabetes and smoking) and therefore progr...
Article
White matter hyperintensities (WMH) are among the most common radiological abnormalities in the ageing population and an established risk factor for stroke and dementia. While common variant association studies have revealed multiple genetic loci with an influence on their volume, the contribution of rare variants to the WMH burden in the general p...
Article
Elucidating the causes of stroke is key to developing effective preventive strategies. The Mendelian randomization approach leverages genetic variants related to an exposure of interest to investigate the effects of varying that exposure on disease risk. The random allocation of genetic variants at conception reduces confounding from environmental...
Preprint
Full-text available
The functional architecture of the brain is composed of distinct networks, where higher system segregation, i.e. greater differentiation of such functional networks, is associated with better cognitive performance. Aging and many neurological diseases have been associated with reduced system segregation and thus cognitive impairment. The genetic ba...
Article
Full-text available
Experimental studies suggest that sodium induced inflammation might be another missing link leading to atherosclerosis. To test the hypothesis that high daily sodium intake induces systemic inflammatory response in humans, we performed a systematic review according to PRISMA guidelines of randomized controlled trials (RCTs) that examined the effect...
Article
Full-text available
Emerging evidence from randomized controlled clinical trials (RCTs) suggests that colchicine has cardiovascular benefits for patients with coronary disease, including benefits for stroke prevention. We performed an updated systematic review and meta-analysis of all RCTs reporting on stroke outcomes during the follow-up of patients with a history of...
Article
Purpose of review: To evaluate whether CSF and circulating neurofilament light chain (NFL), a marker of axonal damage, could discriminate Parkinson’s disease (PD) from atypical parkinsonian syndromes (APS). Recent findings: MEDLINE and SCOPUS were systematically searched, and fifteen studies were included (1035 PD patients,930 APS patients). CSF a...
Article
Full-text available
Background/aim: An alarming increase in vitamin D deficiency even in sunny regions highlights the need for a better understanding of the genetic background of the vitamin D endocrine system and the molecular mechanisms of gene polymorphisms of the vitamin D receptor (VDR). In this study, the serum levels of 25(OH)D3 were correlated with common VDR...
Article
Full-text available
Abstract The aim of this study was to explore the association between genetically predicted circulating levels of immunity and inflammation, and the risk of Alzheimer’s disease (AD) and hippocampal volume, by conducting a two-sample Mendelian Randomization Study. We identified 12 markers of immune cells and derived ratios (platelet count, eosinophi...
Preprint
Full-text available
Rationale The CC-chemokine ligand-2 (CCL2)/ CC-chemokine receptor-2 (CCR2) axis governs monocyte recruitment to atherosclerotic lesions. Coherent evidence from experimental studies employing genetic deletion of CCL2 or CCR2 and human epidemiological studies support a causal involvement of the CCL2/CCR2 axis in atherosclerosis. Still, preclinical st...
Article
Objective To determine whether MCP-1 (monocyte chemoattractant protein 1) levels in human atherosclerotic plaques associate with plaque vulnerability features. Approach and Results We measured MCP-1 levels in human atherosclerotic plaque samples from 1199 patients in the Athero-EXPRESS Biobank who underwent endarterectomy for treatment of carotid...
Article
Observational studies exploring whether there is a nonlinear effect of blood pressure on cardiovascular disease (CVD) risk are hindered by confounding. This limitation can be overcome by leveraging randomly allocated genetic variants in nonlinear Mendelian randomization analyses. Based on their association with blood pressure traits in a genome-wid...
Preprint
Full-text available
White matter hyperintensities (WMH) are among the most common radiological abnormalities in the ageing population and an established risk factor for stroke and dementia. While common variant association studies have revealed multiple genetic loci with an influence on WMH volume, the contribution of rare variants to WMH burden in the general populat...
Preprint
Full-text available
Objective: To determine the association between circulating interleukin-6 (IL-6) levels and risk of incident ischemic stroke in the general population. Methods: Following the PRISMA guidelines, we systematically searched the literature for population-based prospective cohort studies exploring the association between circulating IL-6 levels and risk...
Article
Introduction: Midlife clustering of vascular risk factors has been associated with late-life dementia, but causal effects of individual biological and lifestyle factors remain largely unknown. Methods: Among 229,976 individuals (mean follow-up 9 years), we explored whether midlife cardiovascular health measured by Life's Simple 7 (LS7) is associ...
Article
In Reply We thank Eroğlu and Eroğlu for their interest in our article¹ and for discussing endothelial calcium influx as a potential mechanism underlying the observed association between serum monocyte-chemoattractant protein–1 (MCP-1) levels and cardiovascular mortality. While this is an interesting hypothesis, we feel there are limited data to sup...
Article
Full-text available
Aims: We performed a Mendelian randomization (MR) study to elucidate the associations of ever smoking, lifelong smoking duration, and smoking cessation with heart failure (HF) risk. Methods and results: We extracted genetic variants associated with smoking initiation, age at initiation of regular smoking, cigarettes per day, and smoking cessatio...
Article
Background: Monocyte chemoattractant protein-1 (MCP-1) is a chemokine recruiting monocytes to the atherosclerotic plaque. Experimental, genetic, and epidemiological data support a key role of MCP-1 in atherosclerosis. Yet, the translational potential of targeting MCP-1 signaling for lowering vascular risk is limited by the lack of data on plaque MC...
Article
Drugs whose targets have genetic evidence to support efficacy and safety are more likely to be approved after clinical development. In this paper, we provide an overview of how natural sequence variation in the genes that encode drug targets can be used in Mendelian randomization analyses to offer insight into mechanism-based efficacy and adverse e...
Article
Drugs whose targets have genetic evidence to support efficacy and safety are more likely to be approved after clinical development. In this paper, we provide an overview of how natural sequence variation in the genes that encode drug targets can be used in Mendelian randomization analyses to offer insight into mechanism-based efficacy and adverse e...
Article
Background and Purpose Assessing whether modifiable risk factors are causally associated with stroke risk is important in planning public health measures, but determining causality can be difficult in epidemiological data. We evaluated whether modifiable lifestyle factors including educational attainment, smoking, and body mass index are causal ris...
Article
Drugs whose targets have genetic evidence to support efficacy and safety are more likely to be approved after clinical development. In this paper, we provide an overview of how natural sequence variation in the genes that encode drug targets can be used in Mendelian randomization analyses to offer insight into mechanism-based efficacy and adverse e...
Article
Full-text available
Aims/hypothesis Our aim was to investigate the relationship between average blood glucose levels and incident CHD in individuals without diabetes mellitus. Methods To investigate average blood glucose levels, we studied HbA 1c as predicted by 40 variants previously shown to be associated with both type 2 diabetes and HbA 1c . Linear and non-linear...
Article
Full-text available
Objective We employed Mendelian randomization (MR) to explore the effects of genetic predisposition to type 2 diabetes (T2D), hyperglycemia, insulin resistance, and β-cell dysfunction on risk of stroke subtypes and related cerebrovascular phenotypes. Methods We selected instruments for genetic predisposition to T2D (74,124 cases, 824,006 controls)...
Article
Objective To determine whether functional MRI connectivity can predict the long-term cognitive functions 36 months after minor stroke. Methods Seventy-two participants with first-ever stroke were included at baseline and followed up for 36 months. A ridge regression machine learning algorithm was developed and used to predict cognitive scores 36 m...
Article
Observational studies have shown an association between hypertension and atrial fibrillation (AF). Aggressive blood pressure management in patients with known AF reduces overall arrhythmia burden, but it remains unclear whether hypertension is causative for AF. To address this question, this study explored the relationship between genetic predictor...
Article
Background Observational studies have indicated that depression is associated with coronary artery disease (CAD) and myocardial infarction. Nevertheless, causal associations between depression and cardiovascular diseases remain controversial. Hence, we conducted a Mendelian randomization and mediation analysis to evaluate the associations of depres...
Preprint
Full-text available
Background Interleukin-6 (IL6) signaling is a key inflammatory pathway widely implicated in the pathogenesis of multiple diseases including autoimmune, vascular, and metabolic disorders. While IL6-receptor (IL6R) inhibitors are already in use for the treatment of autoimmune diseases, their repurposing potential and safety profile is still debated....
Article
Full-text available
Importance Observational studies highlight associations of C-reactive protein (CRP), a general marker of inflammation, and interleukin 6 (IL-6), a cytokine-stimulating CRP production, with individual depressive symptoms. However, it is unclear whether inflammatory activity is associated with individual depressive symptoms and to what extent metabol...
Preprint
Full-text available
Monocyte chemoattractant protein-1 (MCP-1) recruits monocytes to the atherosclerotic plaque. While experimental, genetic, and observational data support a key role of MCP-1 in atherosclerosis, the translational potential of targeting MCP-1 signaling for lowering vascular risk is limited by the lack of data on plaque MCP-1 activity in human atherosc...
Article
INTRODUCTION: Microstructural alterations as assessed by diffusion tensor imaging (DTI) are key findings in both Alzheimer’s disease (AD) and small vessel disease (SVD). We determined the contribution of each of these conditions to diffusion alterations. METHODS: We studied six samples (N=365 participants) covering the spectrum of AD and SVD, incl...
Preprint
Importance: Observational studies have shown an association between hypertension and atrial fibrillation (AF). Aggressive blood pressure management in patients with known AF reduces overall arrhythmia burden, but it remains unclear whether hypertension is causative for AF. Objective: The primary objective of this study was to investigate the relati...
Article
Full-text available
Hypertension is the leading risk factor for stroke. Yet, it remains unknown whether blood pressure pulsatility (pulse pressure [PP]) causally affects stroke risk independently of the steady pressure component (mean arterial pressure [MAP]). It is further unknown how the effects of MAP and PP on stroke risk vary with age and stroke cause. Using data...
Article
Full-text available
Background Elevated blood pressure is a major cause of cardiovascular morbidity and mortality. However, it is not known whether midlife blood pressure affects later life cardiovascular risk independent of later life blood pressure. Methods and Results Using genetic association estimates from the UK Biobank and CARDIoGRAMplusC4D consortium, univari...
Article
Full-text available
Objective We employed Mendelian randomization to explore whether the effects of blood pressure (BP) and BP-lowering through different antihypertensive drug classes on stroke risk vary by stroke etiology. Methods We selected genetic variants associated with systolic and diastolic BP and BP-lowering variants in genes encoding antihypertensive drug t...
Article
Full-text available
Background and Purpose Left ventricular hypertrophy (LVH) is associated with the risk of stroke and dementia independently of other vascular risk factors, but its association with cerebral small vessel disease (CSVD) remains unknown. Here, we employed a systematic review and meta-analysis to address this gap. Methods Following the MOOSE guidelines...
Article
Objective Leveraging large-scale genetic data, we aimed to identify shared pathogenic mechanisms and causal relationships between impaired kidney function and cerebrovascular disease phenotypes. Methods We used summary statistics from genome-wide association studies (GWAS) of kidney function traits (chronic kidney disease diagnosis, estimated glom...
Article
Full-text available
Background Previous studies have examined whether steroid hormone treatment in transgender individuals may affect cognitive function; yet, their limited power does not allow firm conclusions to be drawn. We leveraged data from to-date literature aiming to explore the effect of gender-affirming hormone administration on cognitive function in transge...
Article
Full-text available
IntroductionWe used data from MOBI-Kids, a 14-country international collaborative case–control study of brain tumors (BTs), to study clinical characteristics of the tumors in older children (10 years or older), adolescents and young adults (up to the age of 24).Methods Information from clinical records was obtained for 899 BT cases, including signs...
Preprint
Full-text available
Aims: Assessing whether modifiable risk factors are causally associated with reduced stroke risk is important in planning public health measures, but determining causality can be difficult in epidemiological data. Leveraging large-scale genetic data in a technique known as Mendelian randomisation, we aimed to determine whether modifiable lifestyle...
Article
Background and aim: Although clinical trials suggest that colchicine may reduce risk of vascular events in patients with a history of coronary artery disease, its effect on the prevention of cerebrovascular events still remains unclear. Methods: We performed a systematic review and meta-analysis of all available to date randomized-controlled cli...
Article
Full-text available
Blood lipids are causally involved in the pathogenesis of atherosclerosis, but their role in cerebral small vessel disease remains largely elusive. Here, we explored associations of genetic determinants of blood lipid levels, lipoprotein particle components, and targets for lipid-modifying drugs with small vessel disease phenotypes. We selected gen...
Article
Season of birth, a surrogate of seasonal variation of environmental exposures, has been associated with increased risk of several cancers. In the context of a Southern‐Eastern Europe (SEE) consortium, we explored the potential association of birth seasonality with childhood (0‐14 years) central nervous system (CNS) tumors. Primary CNS tumor cases (...
Preprint
Full-text available
Rationale: Type 2 diabetes mellitus (T2D) is an established risk factor for cerebrovascular disease but the mechanisms underlying this association remain elusive. Disentangling the causal effects of T2D, hyperglycemia, and pre-diabetic phenotypes (insulin resistance, β-cell dysfunction) on major etiological stroke subtypes (ischemic stroke, intrace...
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Full-text available
Introduction: The Meta VCI Map consortium performs meta-analyses on strategic lesion locations for vascular cognitive impairment using lesion-symptom mapping. Integration of data from different cohorts will increase sample sizes, to improve brain lesion coverage and support comprehensive lesion-symptom mapping studies. Methods: Cohorts with avai...
Preprint
Full-text available
Background: Studies in humans and experimental models highlight a role of interleukin-6 (IL-6) in cardiovascular disease. Indirect evidence suggests that inhibition of IL-6 signaling could lower risk of coronary artery disease. However, whether such an approach would be effective for ischemic stroke and other cardiovascular outcomes remains unknown...
Article
Rationale: Pro-inflammatory cytokines have been identified as potential targets for lowering vascular risk. Experimental evidence and Mendelian randomization suggest a role of monocyte-chemoattractant protein-1 (MCP-1) in atherosclerosis and stroke. However, data from large-scale observational studies are lacking. Objective: To determine whether...