Molecular and Systems Epidemiology

Molecular and systems epidemiology is an innovative research line that integrate large-scale molecular and omics data into computational models and epidemiologic studies to uncover contributors to complex diseases across multiple levels and explores their interactions.

Traditional epidemiology has effectively identified associations between exposures and diseases in populations but often lacks insights into the biological processes underlying these associations. Molecular and systems epidemiology bridges this gap, enhancing measurements of exposure, effect, and susceptibility, and provides deeper insights into complex biological mechanisms, enabling the generation of novel hypotheses about disease processes. This approach facilitates the identification of early etiologic, diagnostic, and prognostic markers, refines preventive strategies, and paves the way for new therapeutic developments.

The advent of high-throughput omics technologies and access to biobanks from population-based cohort studies have revolutionized epidemiological studies. By integrating various omics datasets, researchers can build dynamic models of molecular changes in complex diseases, driving biomarker and drug discovery.

Our research in the Molecular and systems epidemiology group focuses primarily on the identification of genetic determinants and potential biomarkers for common age-related diseases, such as Alzheimer’s disease and fatty liver. To this end, we integrate multi-omics data from cohort studies like the Rotterdam Study with ~18,000 elderly participants, employ advanced statistical methods, including Mendelian randomization and machine learning, and complement epidemiological data with state-of-the-art molecular and cellular models.

Collaboration is key to our work. Partnerships with several international consortia and initiatives in the field, such as CHARGE, X-OMICS, BIOS/BBMRI-NL, MODEM, COMETS, NUTRICA, and EpicRNA, and collaborations with numerous universities worldwide enable the replication and validation of our findings, ensuring robust and impactful outcomes.

Some of our selected projects include:

Through a comprehensive study of genetic regulation and disease associations of plasma circulatory microRNAs using population-level data, we identify 3292 associations between 1289 SNPs and 63 miRNAs, of which 65% are replicated in two independent cohorts. We demonstrated that plasma miR-eQTLs co-localise with gene expression, protein, and metabolite-QTLs, which help in identifying miRNA-regulated pathways. We then investigated consequences of alteration in circulating miRNA levels on a wide range of clinical conditions in phenome-wide association studies and Mendelian randomisation using the UK Biobank data, which revealed the pleiotropic and causal effects of several miRNAs on various clinical conditions.

Conducting large-scale epigenome-wide association studies on coffee and tea consumption in the CHARGE consortium (>16000 subjects in 15 cohorts), we found DNA methylation-sites associated with coffee intake, some of which were causally linked to the risk of metabolic diseases such as fatty liver.

Exploring novel biomarkers of Alzheimer’s disease (AD) and their rates of change during ~14 years follow-up in >5,000 participants of the Rotterdam Study, we found plasma levels of NfL and amyloid-β42 proteins as potential biomarkers to assess risk of developing AD 10 years in advance in non-demented people.

Leveraging data from the largest available genome-wide association study of Alzheimer’s disease (AD) and performing various in-silico and in-vitro studies, we demonstrated microRNA-142 located on the 17q22 locus to be involved in the pathogenesis of AD by targeting several important Ad-related genes.

https://www.ncbi.nlm.nih.gov/pubmed/?term=mohsen+ghanbari

https://scholar.google.com/citations?user=pwJpmOQAAAAJ&hl=nl

Within Erasmus MC

With the multidisciplinary aspects of our research, we have close collaborations with a range of clinical and biological parties within Erasmus MC including departments of Immunology, Gastroenterology, Neuroscience, Internal Medicine, and Genetic identification.

Outside of Erasmus MC

The Rotterdam Study is one of the main collaborators in several national and international consortia in the field of Molecular Epidemiology (e.g. BBMRI-NL, X-omics, and CHARGE) and the group is currently involved in numerous international multicenter projects.

• NUTRICA grant, A ERA4HEALTH European partnership grant under the NutriBrain program, aimed at modulating brain-aging through nutrition and lifestyle. One of the four main investigators, 2025-2027.
• MODEM grant, A national multi-centric grant for understanding Mechanisms of Dementia, Co-investigator, 2022-2027
• Alzheimer Nederland grant, Role of non-coding RNAs in metabolic pathways underlying Alzheimer’s disease, Main investigator, 2022-2024.
• Erasmus MC Fellowship, Atlas of genetic architecture and disease association of microRNAs, Main Investigator, 2022-2026.
• SOPHIA grant, A multi-centric H2020 grant for Obesity, Co-investigator, 2020-2024
• An NIH grant for Gene-lifestyle interaction analysis, Co-investigator, 2021-2023
• Janssen Prevention Center Leiden, Collaboration on Prevention Biomarkers, Co-Investigator, 2017-2020.
• Alzheimer Nederland travel grant, Casual Inference and Alzheimer’s disease, 2018
• European Fellowship for study of the Diabetes, Visiting Imperial College London, 2018
• European Society of Human Genetics fellowship, for advanced courses in Human Genetics, 2016
• Iranian Ministry of Health and Medical Education Scholarship, 4-year fund for PhD research, 2011-2015

Principle Investigator:

Mohsen Ghanbari, m.ghanbari@erasmusmc.nl

Management Assistant:

Maaike Oomens, m.oomens@erasmusmc.nl

Postdoc researchers:

Eliana Portilla Fernandez (2019-2020)

Ivana Prokic-Nedeljkovic (2019-2021)

Shahzad Ahmad (2020-2022)

Lisa van der Burgh (2022-2023)

Pooja Mandaviya (2022-2024)

PhD students:

Silvana Maas, Epigenetics and lifestyle factors, (2017-2019)

Michelle Mens, Circulatory miRNAs and age-related disorders, (2017-2021)

Xiaofang Zhang, Genetics of fatty liver disease, (2017-2022)

Irma Karabegovic, Epigenetics and lifestyle factors, (2021-2022)

Yasir Abozaid , Metabolic pathways and liver diseases, (2019-2022)

Amber Yaqub, Longevity and Alzheimer’s disease, (2019-2023)

Ziyi Xiong, Improving genetic Epi approaches, (2019-2023)

Ibrahim Ayada, Genetic of NAFLD and MAFLD, (2021-2024)

Yu Shuai, Genetic and epigenetic regulation of cancer, (2021-2025)

Sam Leonard, Immuno-omics and immune-related disorders (2022-2024)

Mina Shahisavandi, Pharmaco-metabolomics and metabolic disorders (2022-2025)

Midas Kuilman, Mechanisms of Alzheimer’s disease (2023-2026)

MSc students:

Meghan Murphy, Association of serum HSV titer and risk of dementia (2018-2019)

Silvana Maas, DNA methylation and smoking (2017-2019)

Irma Karabegovic, DNA methylation and coffee consumption (2017-2019)

Sam Leonard, Genetic and metabolomics of Immune markers (2021-2022)

Enping Wang, multi-omics analysis of COVID-19 (2021-2023)

Georgia Malliou, Metabolomics and vascular calcification (2022-2023)

Mina Shahisavandi, Pharmaco-metabolomics (2022-2023)

Midas Kuilman, MicroRNAs and Depression (2023-2024)