Group leader

Adrian Tett

Adrian Tett is a Group leader at the Centre for Microbiology and Environmental Systems Science, University of Vienna, Austria. The group focuses on the utilization of computational approaches combined with metagenomics to understand the human microbiome in fine detail. Specifically, to explore the hidden diversity in novel species and sub-species and their relationship to health or disease. We exploit thousands of human metagenomes across populations and lifestyles in large scale metanalyses to identify and target potentially important microbiome members for further analysis and characterisation. Another interest is utilising ancient microbial fossils and pre-industrialised populations to determine how the process of Westernisation has dramatically and rapidly changed our co-evolved human microbiome and the potential implications this may have to health.
Reader in Neurology & Neuroepidemiology

Alastair Noyce

Alastayr Noyce is a Reader in Neurology & Neuroepidemiology and a neurologist and epidemiologist interested in the risk factors and determinants of neurological diseases.

Abstract of the talk

Determinants of Parkinson’s disease – genes, environment and interactions

This talk will begin with a discussion the apparent rising global burden of Parkinson’s disease (PD). I will summarise what we know about the genetic basis of PD and also what we know about environmental risk factors. I will talk about how midlife comorbidities may contribute to PD risk and progression. I will then explore the dichotomy of genetic versus environmental risk factors for PD, and how one can tell us about the other, and what evidence exists for interactions between them. I will finish by talking about future perspectives and ongoing projects.

Research Director

Anne Puel

Paul Wilmes is Professor of Systems Ecology and holds appointments at the Luxembourg Centre for Systems Biomedicine and in the Department of Life Sciences and Medicine within the Faculty of Science, Technology and Medicine of the University of Luxembourg. He heads the Systems Ecology Research Group. During the COVID-19 pandemic, Paul acted as co-speaker of the COVID-19 Task Force of Research Luxembourg and was appointed “chargé de mission” by the University of Luxembourg. As a British Chevening Scholar, Paul earned his PhD from the School of Environmental Sciences at the University of East Anglia (UK). For part of his doctoral research, he spent time as a German Academic Exchange Service Visiting Scientist at the Max Planck Institute for Marine Microbiology in Bremen (Germany). Paul subsequently carried out postdoctoral research at the University of California, Berkeley (USA) from where he returned in 2010 to his native Luxembourg through the ATTRACT fellowship scheme of the Luxembourg National Research Fund. Paul was awarded an European Research Council (ERC) Consolidator Grant in 2019. He is an elected full member of the Institut Grand-Ducal, Section des Sciences naturelles, physiques et mathématiques, and the Académie Lorraine des Sciences. In 2018, Paul was awarded the Grand Prix in Biological Sciences of the Institut Grand-Ducal. Paul has authored more than 120 peer-review publications and is a Highly Cited Researcher. He is a frequently invited speaker at international scientific symposia and academic institutions.

Abstract of the talk

Human genetic and immunological host factors in critical COVID-19 pneumonia

Most individuals, following infection with SARS-CoV-2 will be asymptomatic or develop a benign infection. However, approximately 10% of the infected cases will develop hypoxemic COVID-19 pneumonia, leading to critical disease in around 3% of cases. The resultant risk of death (approximately 1% across age and gender) doubles every five years from childhood onwards and is around 1.5 times greater in men than in women. The molecular and immunological host factors of critical COVID-19 pneumonia will be discussed, in particular, inborn errors of type I interferons (IFNs), found 1-5% of patients with critical pneumonia and neutralizing auto-antibodies against IFN-α, IFN-β and/or IFN-ω, found in approximately 15-20% of patients with critical pneumonia.

Academic Medical Oncologist

Benjamin Fairfax

Benjamin Fairfax is an Academic Medical Oncologist based in Oxford specialising in the treatment of skin cancer, qualified in Medicine in 2006, intercalating a PhD in Pharmacology at UCL. As a junior doctor he became interested in the causes of heterogeneity response to infection and undertook a Wellcome MB PhD postdoctoral fellowship in Julian Knight’s group in Oxford where he developed research interests in cell-type specific and context-specific expression quantitative trait loci (eQTL) in the immune system. He was awarded a Wellcome Clinical Fellowship to establish a research group at the MRC WIMM in 2017. The focus of their work is the identification of peripheral markers of response to checkpoint immunotherapy given to treat cancer. They are particularly interested in the interaction of treatment with germline genetic variation to both shape the immune response to tumours and potentially predispose to autoimmune side effects. Other key projects within the group include the agnostic identification of T cell receptor sequences associated with complete response to treatment and the interplay with patient HLA type. They hope that their work will help in the development of novel adjuncts to cancer immunotherapy as well as further the understanding of the mechanistic basis of autoimmunity.

Abstract of the talk

Exploring the interplay between germline genetic variation and responses to cancer immunotherapy and chronic viral infection across a large patient cohort

We have characterised variation in the longitudinal peripheral immune response to anti-PD1 checkpoint immunotherapy given to treat melanoma in a cohort of >250 patients using both transcriptomics (cell-specific bulk RNAseq, adaptive immune receptor sequencing and single-cell RNAseq) and immunological methods (high-throughput flow-cytometry). By integrating these data with long-term clinical outcomes, we are able to identify a number of peripheral immune features that show association with long-term complete responses to treatment, as well as predisposition to autoimmune toxicity in the pre-treatment state. Interestingly, we find germline genetic variation interacts with both having cancer, as well as response to immunotherapy to modulate gene expression – allowing us to identify eQTL specific to these states, as well as chronic viral infection (CMV). I will demonstrate the identification of one such cancer-specific eQTL that is associated with B cell expression of the key lymphopoietic cytokine IL7, carriage of which regulates the pan-cellular responses to anti-PD1 treatment and predisposes to treatment related autoimmune toxicity.

Professor of Psychiatric Epidemiology

Brenda Penninx

Brenda Penninx is Professor of Psychiatric Epidemiology at the Department of Psychiatry of the Amsterdam UMC, Vrije Universiteit in the Netherlands. Her focus is on cross-disciplinary mental health research which integrates psychiatry, psychology, neuroimaging, genomics, psychoneuroendocrinology, sociology and behavioural medicine. She leads the multi-site, longitudinal Netherlands Study of Depression and Anxiety (www.nesda.nl), an invaluable research resource for psychiatry which so far yielded >68 PhD-theses and >600 publications. Her work is exemplary in transforming and enhancing the value of longitudinal cohort studies to better understand the multi-nature origin and longitudinal trajectories of stress-related disorders. For this, she embeds big-data ‘omics’ and real-world ambulatory assessments of behaviour and emotions in her studies. My work on immunometabolic depression provides novel insights into depression’s heterogeneity and helped to pave the way towards designing new personalised interventions. Funded through prestigious national or EU-grants, Her research team consists of 4 Assistant Professors, 6 Post-docs and 15 PhD-students, with over 60 PhD-students having obtained their PhD-degree thorugh Penninx’ supervision. In 2016, Penninx was elected member of the Royal Dutch Academy of Sciences and Arts.

Abstract of the talk

Using genetics to unravel the heterogeneity of depression

The burden on society by depression is undisputable. This large burden is partly due to a course pattern that is more chronic than often assumed, and the large heterogeneity of depression contributes to non-response to our standardly available treatments. Using data from the Netherlands Study of Depression and Anxiety (NESDA, www.nesda), Penninx will illustrate both points. NESDA has followed >3000 adults, including many patients with depression and/or anxiety disorders, over 13 years of follow-up. When looking at its long-term course, especially when also considering the transitions into other affective disorders over time, it has been found that chronicity is more the rule than the exception (Verduijn et al. BMC Med 2017). Taking heterogeneity of depression into account could lead to precision psychiatry approaches that help reduce depression’s chronicity. Using NESDA data, Penninx’s team has consistently found that immuno-metabolic dysregulations vary as a function of depression heterogeneity: dysregulations map more consistently to “atypical” neurovegetative symptoms reflecting altered energy intake/expenditure balance (hyperphagia, weight gain, hypersomnia, fatigue and leaden paralysis). Such findings are confirmed when utilizing with genetic data, including genome-wide gene expression as well as DNA available in NESDA as well as in larger general population based studies (e.g. UK Biobank). Some preliminary treatment studies further suggest that the presence of immuno-metabolic dysregulations in depressed persons may moderate antidepressant effects of standard or novel (immunomodulatory) interventions. So, an immuno-metabolic depression dimension could dissect depression’s heterogeneity and potentially match depressed subgroups to treatments with higher likelihood of clinical success. Overall, NESDA findings also point out the relevance of dissecting the heterogenous group of depressed persons so that personalized medicine strategies could contribute to reducing the chronic nature and disease burden of depression.

Senior Researcher in Pharmacoepidemiology & Lecturer of Psychiatry

Christiane Gasse

Christians Gasse is a senior researcher in pharmacoepidemiology and lecturer of psychiatry at the Department of Affective Disorders and the Psychosis Research Unit, Aarhus University Hospital Psychiatry, Denmark. Educated as a pharmacist and a PhD in pharmacoepidemiology, for the last 15 years, her main areas of research have been psychopharmacology and pharmacogenetics in people with psychiatric disorders using the comprehensive Danish population-based registers. She is particularly interested in extending and translating pharmacogenetics into clinical practice to support the personalized medicine approach in psychiatry in Denmark and internationally, also through collaborations with psychiatric institutions and genomic biobanks in Europe and Canada.

Abstract of the talk

From associations to clinical utility: impact of functional CYP2C19 and CYP2D6 gene variants on treatment in patients with depression: a Danish cohort study

Convincing evidence of the utility of pharmacogenetic (PGx) testing in clinical practice is still limited. Here we present population-based findings of the associations of CYP2D6 and -2C19 variants with antidepressant treatment outcomes, including switching, emergency department contacts, and suicide attempt or self-harm in young people with depression.

We studied all individuals born in Denmark between 1981 and 2006 (N=17,297) diagnosed with depression at a psychiatric hospital and using selected antidepressants. Using array-based single-nucleotide-polymorphism genotype data, the CYP2D6 and -2C19 genotypes of these individuals were translated into metabolizer phenotypes categorized into CYP2C19/CYP2D6 normal (NM, reference group), ultra-rapid- (UM), rapid- (RM), intermediate- (IM), or poor-metabolizer (PM) status according to the Dutch Pharmacogenetics Working Group and the Clinical Pharmacogenetics Implementation Consortium. We followed all individuals from their first prescription of es-/citalopram, sertraline and fluoxetine until the occurrence of a treatment outcome within 1-year applying Poisson regression analysis adjusted for confounders, including sex and age and co-medication and comorbidity.

Children with CYP2C19 PM status using (es)citalopram had increased risks of switching (Incidence Rate Ratio (IRR) 1.64 [95% confidence interval (CI): 1.10-2.43]), and of suicide attempt or self-harm (IRR 2.67 [95% CI; 1.57-4.52]). Young adults with CYP2C19 PM status (19-25 years) using sertraline had an increased risk of switching (IRR 2.06 [95% CI; 1.03-4.11]). Young adults with CYP2D6 PM status using fluoxetine had an increased risk of emergency department contacts (IRR 3.28 [95% CI; 1.11-9.63]). No statistically significant associations were detected in adults aged 26 to 37 years, potentially due to low power. In conclusion, CYP2C19 and CYP2D6 PM phenotypes were associated with outcomes of treatment with antidepressants in children and younger adults with depression indicating the benefit from PGx testing for PGx guided treatment at younger ages.

Professor of Computational Medicine

Claudia Langenberg

Claudia Langenberg is Professor of Computational Medicine at the Berlin Institute of Health at Charité (BIH) and MRC Investigator and Programme Leader at the MRC Epidemiology Unit at the University of Cambridge. Her research is focused on the genetic basis of metabolic control, and her team studies its effects on health through integration of molecular with clinical data in large-scale patient and population-based studies.

Abstract of the talk

From molecules to health records: utility of omics at population scale

Application of different omic technologies is now feasible at population scale. This talk will present examples of how the integration of different omics in large patient and population studies can help to predict disease risk, understand mechanisms, and reveal shared connections between different diseases.

PhD, Professor, Director

Dario Greco

Dario Greco is professor of bioinformatics at the Faculty of Medicine and Health Technology, Tampere University and the director of FHAIVE, The Finnish Hub for Development and Validation of Integrated Approaches. He is also principal investigator at the Institute of Biotechnology, University of Helsinki, Finland and the coordinator of the Finnish 3R Centre. To date, he authored over 170 articles in peer reviewed journals in the areas of nanotoxicology, toxicogenomics, drug repositioning, network biology, data modelling and bioinformatics which were cited over 8,000 times (h-index 44). To date, he has completed the supervision of 10 PhD theses. FHAIVE is currently composed of 28 scientists, including senior scientists, postdoctoral fellows, PhD and MSc students. Greco currently receives funding from the Academy of Finland, the EU (H2020, Green Deal, ERC, EIC and IMI2 programs), the Novo Nordisk Foundation, the Finnish Red Cross, the Finnish Government and the European Research Council (ERC Consolidator).

Abstract of the talk

Toxicogenomics and IATA for the development of new chemicals drugs, and materials: the FHAIVE experience

Toxicology is undergoing through profound changes as the focus of investigation is shifted from the observation of apical phenomena to mechanistic aspects of the exposure. If on one hand we need to ensure that dangerous chemicals do not emerge, on the other, we also need to promote rapid and sustainable innovation to successfully overcome the modern challenges of humankind. Toxicogenomics aims at clarifying the mechanism of action (MOA) of chemicals by using omics assays. The Adverse Outcome Pathways (AOP) concept is also emerging to contextualise toxicogenomics-derived MOA. Efforts are ongoing to anchor AOPs to molecular assays, but systematic embedding of AOP-derived in vitro tests and Integrated Approaches to Testing and Assessment (IATA) are still unestablished. At the same time, toxicogenomics-based evidence still struggles to gain regulatory acceptance. At the Finnish Hub for Development and Validation of Integrated Approaches (FHAIVE), we develop new IATA (Integrated Approaches for Testing and Assessment) based on big data science, artificial intelligence (AI), network science, toxicogenomics, molecular assays and cell technology via an integrated and comprehensive knowledge graph approach. In this talk, I will present some examples of the advances we are implementing in the field of toxicology and how they can be used in a unified framework to guide the safe-, sustainable- and effective-by-design chemicals, drugs, and materials.

Neurosurgeon

Dietmar Frey

Dietmar Frey is a board-certified neurosurgeon and founding director of CLAIM – the Charité Lab for AI in Medicine (https://claim.charite.de/en/). After completing law school, he went to Charité Med School and graduated in 2007. In 2014, he completed his specialist training in neurosurgery. He has built a strong interdisciplinary team of physicians, software engineers, machine learning engineers and computer scientists to develop AI-based models  and to implement these models into the clinical workflow for improvement of patient care.

Abstract of the talk

PRECISE4Q

Stroke is one of the most severe medical problems with far-reaching public health and socio-economic impact, gathering momentum in an ageing society. PRECISE4Q set out to minimise the burden of stroke for the individual and for society. Over the course of the last 4 years we developed multi-dimensional data-driven predictive models enabling – for the first time – personalised stroke treatment, addressing patient’s needs in four stages: prevention, acute treatment, rehabilitation and reintegration.

Postdoctoral fellow

Elo Madisson

Elo is experienced in high throughput transcriptomics and has contributed to the cell atlases on lung, oesophagus and spleen within the Human Cell Atlas consortia. Her most recent work as an ESPOD postdoctoral fellow in high throughput tissue transcriptomics at Wellcome Sanger Institute (Sarah Teichmann) and European Bioinformatics Institute (Oliver Stegle) focused on comprehensive single cell and spatial atlasing of the human lung and airways. With the focus on tissue immunity, Elo’s most recent work in human airways unravelled a gland-associated immune niche by combining single cell & nuclei RNA-seq, VDJ-seq and Visium Spatial transcriptomic methods when studying the microanatomy of the tissue.

Abstract of the talk

A spatial multi-omics atlas of the human lung reveals a novel gland-associated immune niche

To better understand lung function and immunity, we have generated a multi-omics single cell, nuclei and Visium Spatial Transcriptomics data set for 5 proximal-to-distal locations of the human lung. Our atlas defines novel cell types/states which we map back into the macro- and micro-anatomical tissue context, including distinct pericyte and smooth muscle subtypes, immune-recruiting fibroblasts, peribronchial and perichondrial fibroblasts, peripheral nerve associated fibroblasts, Schwann cells and submucosal gland (SMG) duct cells. Using our atlas we define a survival niche for IgA-secreting plasma cells at the SMG, comprising the newly defined epithelial SMG-Duct cells, along with SMG-Serous cells and B and T lineage immune cells. We propose a signalling circuit that establishes and supports this niche. Our online resource for data browsing, automated cell type annotation and spatial mapping of genes will facilitate the study of tissue microenvironments such as the newly defined gland-associated immune niche (GAIN).

Deputy Director General, EMBL & Director, EMBL-EBI

Ewan Birney

Ewan Birney is Deputy Director General of EMBL and Director of EMBL-EBI.

Ewan completed his PhD at the Wellcome Sanger Institute with Richard Durbin. In 2000, he became Head of Nucleotide data at EMBL-EBI and in 2012 he took on the role of Associate Director at the institute. He became Director of EMBL-EBI in 2015. Ewan led the analysis of the Human Genome gene set, mouse and chicken genomes and the ENCODE project, focusing on non-coding elements of the human genome. Ewan’s main areas of research include functional genomics, DNA algorithms, statistical methods to analyse genomic information (in particular information associated with individual differences in humans and Medaka fish) and use of images for chromatin structure.

Ewan is a non-executive Director of Genomics England, and a consultant and advisor to a number of companies, including Oxford Nanopore Technologies and Dovetail Genomics. Ewan was elected an EMBO member in 2012, a Fellow of the Royal Society in 2014 and a Fellow of the Academy of Medical Sciences in 2015.

He has received a number of awards including the 2003 Francis Crick Award from the Royal Society, the 2005 Overton Prize from the International Society for Computational Biology and the 2005 Benjamin Franklin Award for contributions in Open Source Bioinformatics. On December 29, Ewan Birney was made a Commander of the British Empire (CBE) as part of the Queen’s New Year’s Honours List for 2019. Ewan received the honour in recognition of his services to computational genomics and leadership across the life sciences.

Abstract of the talk

Molecular biology is now a leading example of a data intensive science, with both pragmatic and theoretical challenges being raised by data volumes and dimensionality of the data. These changes are present in both “large scale” consortia science and small scale science, and across now a broad range of applications – from human health, through to agriculture and ecosystems. All of molecular life science is feeling this effect.

This shift in modality is creating a wealth of new opportunities and has some accompanying challenges. In particular there is a continued need for a robust information infrastructure for molecular biology. This ranges from the physical aspects of dealing with data volume through to the more statistically challenging aspects of interpreting it. A particular problem is finding causal relationships in the high level of correlative data. Genetic data are particular useful in resolving these issues.

The pandemic has brought together operational public health delivery (eg, testing and DNA sequencing of the infectious agent) alongside research and models. The rate of learning has increased between these two domains and delivered better and better products for both policy makers and research. I will illustrate this with examples including the expansion of the Alpha and Delta SARS-CoV-2 genomes and integrating genomic and contact tracing work.

Group leader and Associate professor

Hannes Schroeder

Hannes is group leader and associate professor at the Globe Institute, University of Copenhagen. His research group works at the intersection of archaeological, population genomics, and microbial ecology and uses genome-scale data to tackle unresolved questions relating to the human past and the history of infectious diseases. He has worked in many different regions of the world and his most recent work includes the first population-level ancient human DNA study in the Caribbean and his group’s work on ancient “chewing gums” as a new source of ancient human and microbial DNA.

Abstract of the talk

Challenges and prospects in ancient metagenomcis

For years the field of ancient DNA was dominated by human ancient DNA studies. More recently, the study of ancient metagenomes has started to provide fascinating, millennial-scale insights into the evolution of particular pathogens and changes in the composition and function of entire microbial communities or microbiomes. However, the analysis of ancient metagenomes is challenging as, just like human DNA, the DNA of interest is usually degraded and, depending on the sample type, present in low abundance. One of the biggest challenges facing ancient metagenome studies is the presence of modern contamination – both in terms of postdepositional contamination of samples and the presence of contamination in modern reference genomes – which can result in false positive identifications. In this talk, I will discuss some of the pitfalls and technical challenges related to working with ancient metagenomes, drawing on various case studies from ancient chewing gums to parasites, and discussing some of the methods we and others have developed to address them.

Professor of Epidemiology

Henrik Larsson

Henrik Larsson is Professor of epidemiology at Örebro University, Sweden. The overall objective of his research team’s work on ADHD is to a) identify the occurrence, developmental course, comorbidity patterns across and long-term burden of ADHD; b) identify the benefits and risks associated with ADHD treatment interventions, c) develop risk predictions tools to identify individuals with ADHD at high risk for adverse outcomes; d) explore how genetic and environmental factors influence ADHD across the life-span. Henrik Larsson’s team use large cohorts identified from national health registers, the Swedish twin register and other cohort studies. These datasets contain valid diagnoses of psychiatric diagnosis, prospective measures of environmental risks, quantitative-genetic data (zygosity and family-relationships), high throughput genotyping, longitudinal information on prescribed ADHD medications and assessments of serious medical (psychiatric and somatic problems) and functional (social, educational and occupational) outcomes. Henrik is a faculty member of IMPACT, ECNP, EUNETHYDIS, and the Behavioral Genetic Association and has (co-) authored over 350 original peer-reviewed papers. He is editor-in-chief of JCPP Advances and scientific coordinator of TIMESPAN; a large horizon 2020 project exploring the management of chronic cardiometabolic disease and treatment discontinuity in adults with ADHD.

Abstract of the talk

This presentation aims to:

  1. highlight key findings from our past register-based research on ADHD across the lifespan
  2. show preliminary findings from new Horizon 2020 research program (TIMESPAN) that aims to advance the management of individuals with ADHD and co-occurring cardiometabolic disease
  3. discuss challenges and opportunities with register-based research.
Associate Professor

Anders Eriksson

Dr Eriksson obtained his PhD from University of Gothenburg and joined the department of Marine Ecology as a post-doctoral fellow in 2007. In 2009 he joined the department of Zoology in Cambridge, UK, as a post-doctoral fellow to work on spatially explicit population genetic models. Between 2013 and 2016 the position was shared between Cambridge and King Abdullah University of Science and Technology (KAUST) in Saudi Arabia, where he led the population genetic analysis in the Pan-Asian Genome Initiative (PAPGI). In 2017 he obtained a Lecturer position at Department of Medical and Molecular Genetics at King’s College London, UK. In 2019 he joined the Institute of Genomics at University of Tartu as ERA Chair of the Centre of Genomics, Evolution and Medicine (cGEM). In 2021 he was appointed Associate Professor of Interdisciplinary Research in Genomics. His research combines ancient DNA information with genomic, epigenetic and phenotypic data from population-scale biobanks to investigate how demographic processes and adaptations to past climates, diets and pathogens have shaped complex human traits in contemporary populations and the roles of these changes in common metabolic, cardiovascular and immune mediated diseases.

Abstract of the talk

The influence of population admixtures on the evolution of complex human traits: insights from genomic, phenotypic and functional data

The peopling of Eurasia has been characterised by complex demographic history, including hybridization with archaic hominins and subsequent population movements and admixture. The spread of anatomically modern humans into new environments has been facilitated by a series of adaptations in complex traits but the interplay between dietary, immunological, behavioural and other environmental factors and population movements and contacts in shaping these evolutionary processes is poorly understood. To address this issue, we have leveraged genomic and phenotypic data from population-level biobanks with analysis of DNA from ancient humans and archaic hominins to investigate how genetic variation from ancient human and archaic hominin populations shaped evolution of phenotypic variation in complex human traits. For donors to the Estonian biobank, we found substantial differences in ancestry and evidence of strong recent natural selection for several anthropometric (including height, body mass index and pigmentation of eye and hair), metabolic (blood pressure, heart rate and cholesterol levels), reproductive and sleep-related traits. Furthermore, analysis of Neandertal DNA present in donors to European and East Asian biobanks show population-specific associations with autoimmunity, cancers and type 2 diabetes and long-range regulatory effects on patterns of transcription factor activation in the human genome. These results show the importance of past population contacts and gene flow for the evolution of complex human traits.

Professor of Genetic Epidemiology

Karoline Kuchenbaecker

Karoline Kuchenbaecker is Professor of Genetic Epidemiology at University College London where she leads the “Diversity in Genetics” group. Her research focusses on the genetic and environmental risk factors for diseases by leveraging the unique characteristics of diverse populations. She has developed methodological standards for diverse samples as well as innovative methods to empower locus discovery and to assess transferability of genetic risk factors.

Abstract of the talk

Diversity in genomic studies: the transferability of complex trait loci and its impact on downstream applications

Since the publication of the first human genome sequence two decades ago, millions of genomes have been sequenced or genotyped. However, the vast majority were European ancestry samples. Despite repeated calls for change, representation of diverse populations has not improved over the last years.

In this presentation I will use different data resources and outcomes to assess whether the existing findings from European ancestry samples are transferable to other groups and explore the impact of ancestry and population for downstream applications of genomics including genetic risk prediction and genetically informed causal inference.

Genes and Health (G&H) is a community based, long-term study in British Bangladeshi and British Pakistani people. We used data from 23K participants to characterize the genetic architecture of cardiometabolic traits. Secondly, using data from existing biobanks we have established AnDi, the first large-scale multi-ancestry resource for major depression (MD), a highly complex and polygenic disorder. We used data from 84K cases and 904K controls with diverse ancestry and combined them with data from 258K cases and 574K controls with European ancestry.

The multi-ancestry GWAS of MD identified 190 significant associated loci, 84 of which had not previously been reported. Fine-mapping benefited from the additional sample diversity: the number of credible sets with ≤5 variants increased from 10 to 16 loci. For previously reported depression loci from European ancestry studies, transferability was highest in the Hispanic group with 69 loci (8.6 per 10k effective samples) and lowest in samples with African ancestry when accounting for sample size (37 loci, 3.09 per 10k). On the other hand, we found evidence for transferability for the vast majority of cardiometabolic loci that were sufficiently powered to replicate in G&H: the PAT ratios were all >0.8 for the risk factor traits, but only 0.62 for CAD. The relative accuracy of PGS compared to European ancestry was high for some traits, including HDL-C, but lower for CAD and MD.

In conclusion, we observed evidence that some complex trait loci are specific to certain ancestry groups. We identified novel, biologically plausible associations that were missed in European ancestry analyses and demonstrated that large diverse samples can be important for the identification of target genes and putative mechanisms. This highlights the importance of sincere, concerted global efforts toward genomic equity to ensure the benefits of genomic medicine are accessible to all.

Associate professor in Data Science

Leo Lahti

Leo Lahti is associate professor in Data Science in University of Turku, Finland. His research team focuses on computational analysis of complex natural and social systems and related open data science frameworks. Population studies of the human microbiome have been one of the leading research themes of the team over the past decade. Lahti obtained doctoral degree (DSc) in statistical machine learning and bioinformatics from Aalto University in Finland (2010), developing probabilistic data integration methods for high-throughput life science applications. This was followed by postdoctoral research periods at EBI/Hinxton (UK; Alvis Brazma), Wageningen University (Netherlands; Willem de Vos), and KU Leuven (Belgium; Jeroen Raes). Lahti coordinates international networks in data science methods development, including e.g. R/Bioconductor network and EU/COST action on statistical and machine learning techniques for microbiome studies, organizing international training events on this topic on a regular basis. He is the national delegate in the Committee on Data of the International Science Council and a founder of the open science work group of Open Knowledge Finland ry. For more information, see the research homepage datascience.utu.fi

Abstract of the talk

Emerging computational approaches in population studies of the human microbiome

Microbial communities have been recognized as essential components of our physiology and health. Understanding their role in health and well-being is challenging due to the high temporal and spatial variation in the presence and abundances of microbial strains both within and between individuals. Together with carefully designed intervention studies, the accumulation of population-level research data has opened up new possibilities for understanding individuality against the context of population-level variation. Taking advantage of the current and emerging data resources from complex microbial ecosystems relies on our ability to develop efficient and reliable computational approaches. This talk highlights recent advances in statistics, machine learning, and data science methodology in human microbiome research, with a particular emphasis on integrating microbiome data with other, complementary information sources, modeling temporal and spatial variation, and anticipating long-term disease risk in large populations.

Research Associate Professor

Lisa Bastarache

Lisa Bastarache is a research associate professor at Vanderbilt University Medical Center (VUMC), Nashville, Tennessee, USA. Her work focuses on using electronic health record (EHR) data to advance our understanding of human genetics, increase the diagnostic potential of clinical genetic testing, and identify undiagnosed individuals. As scientific director of a phenotyping core at VUMC, she has collaborated with over 50 physician scientists and investigators to help them use EHR data to address their research questions.

Abstract of the talk

Studying rare variants at the population level: How EHR-linked biobanks give us new insight into monogenic disease

Much of what we know about monogenic disease is based on studies of individuals and their families. Large biobanks that link genetic variants to dense phenotypic information allow us to study these diseases at the population level, leading to new insights into the phenotypic manifestations of genetic disease and the variants that cause them. This talk will focus on methods that enable us to study genetic variants at the population level, give examples of common pitfalls of EHR-based phenotyping, and show how biobanks can be used to derive clinically relevant knowledge that has the potential to help patients.

Principal Researcher

Lu Yi

Dr. Lu Yi is a Principal Researcher at Karolinska Institutet (KI), Sweden, where she leads a research group conducting psychiatric genetics research, especially in major depressive disorder. She is co-directing the KI Psychiatric Genomics Institute and the Nordic Tryggve consortium. Her research excellence has been recognised nationally and internationally, for which she has been awarded many prestigious grants including a recent European Research Council starting grant. The current research she is leading involves integrating large-scale genomic data and nationwide electronic healthcare records to investigate subtypes, such as treatment resistant depression, as a way to reduce the substantial heterogeneity in major depressive disorder. Her long-term research vision is to promote targeted drug development and treatment optimization for depression patient subgroups to achieve precision psychiatry.

Abstract of the talk

A multidisciplinary approach to better understand treatment resistant depression

Major depressive disorder (MDD) is a common psychiatric disorder and a leading cause of disability worldwide. Although current treatments are generally effective, up to one-third of individuals with MDD fail to respond to first line therapies, and are typically referred to as having treatment-resistant depression (TRD). TRD patients have higher rates of mortality, higher health care costs, and are hospitalized longer compared to those with MDD who are treatment responsive. There is considerable motivation to provide more effective care for patients with TRD. Despite its overall burden and clinical importance, studying TRD has been challenging due to unstandardized definitions of TRD and difficulty in ascertaining large samples of these severe cases. These major challenges have largely limited our understanding of its aetiology.

I propose to use a multidisciplinary approach covering epidemiology, genetic epidemiology, gene mapping, and machine learning to systematically investigate TRD. Leveraging powerful resources of the national registries and biobank data, we have a unique opportunity to investigate the genetic and non-genetic factors underlying TRD, and integrate these factors in prediction models aiming to detect TRD early in patients’ treatment history. These steps are essential for achieving the translational goal of enabling personalized therapeutic approach in this disorder, thereby to reduce morbidity, mortality, and suffering in patients with TRD.

Research Director and head of the laboratory

Mart Saarma

Mart Saarma is the Research Director and head of the laboratory at the Institute of Biotechnology, HiLIFE, University of Helsinki. He was in 2015-2016 the Vice President of the European Research Council and in 2011-2016 the member of the EMBO Council. He is the member of several academies, EMBO and Academia Europea. Dr. Saarma group has characterized several new GDNF family receptors, discovered a new neurotrophic factor CDNF. His research group is investigating the signalling and biological functions of GDNF family ligands and endoplasmic reticulum located CDNF/MANF neurotrophic factor families, both within and outside of the nervous system. He is also interested in the therapeutic potential of these proteins in various diseases, so he is testing their efficacy in animal models of Parkinson’s disease, amyotrophic lateral sclerosis, stroke and diabetes mellitus. One of the highlights of his research has been initiation and successful completion of phase I-II clinical trials of CDNF protein in Parkinson’s disease patients by the Finnish company Herantis Pharma Plc. He was also a founder of Mobidiag Ltd. company that was recently sold to Hologic company.

Abstract of the talk

Search for new molecules to cure Parkinson’s disease

Parkinson’s disease (PD) affects about10 million people and no treatment exists that can slow down or stop the disease progression. In PD midbrain dopamine (DA) neurons degenerate and die causing in addition to major motor symptoms also non-motor symptoms. Current drugs can only temporarily alleviate the motor symptoms, but non-motor symptoms remain untreated. Our group has discovered an endoplasmic reticulum (ER) located protein with neurotrophic factor (NTF) activities – cerebral dopamine neurotrophic factors (CDNF). We have solved the three-dimensional structure of CDNF and shown that their structure and mode of action radically differs from other known NTFs. CDNF can protect and repair midbrain DA neurons in rodent and non-human primate neurotoxin models of PD at least as efficiently as other known NTFs. However, differently from other NTFs, CDNF is located in the ER, where they regulate ER stress and unfolded protein response pathways. CDNF knockout (KO) mice develop an age-dependent loss of enteric neurons resulting in pathological changes of gastrointestinal function. The deficiencies of CDNF KO mice are similar to those seen in early stages of Parkinson’s disease. Herantis Pharma Plc. has tested CDNF in phase I-II clinical trials in PD patients and CDNF achieved its primary endpoint of safety and tolerability. Moreover, significant increases in DAT PET signaling and improved UPDRS scores were observed in some, but not all, CDNF-treated patients. Since CDNF cannot pass through the blood – brain barrier (BBB), it is delivered directly into the patient’s brain via catheters that are installed during invasive surgery. We have recently discovered a fragment of CDNF (ngCDNF) that can pass through the BBB after subcutaneous administration. Use of ngCDNF may allow peripheral delivery avoiding intracranial surgery. Considering that CDNF protein doesn’t have optimal properties as a drug, we discovered small compounds which mimic the action of CDNF & its homologous protein MANF. Preliminary data indicate that these compounds regulate ER stress and protect cultured DA neurons from 6-hydroxydopamine induced death.

Professor

Michael Simpson

Michael Simpson is a Professor of Genetics at King’s College London. He leads the Genomic Medicine research group, whose focus is on understanding the genetic mechanisms of human disease. He has a specific interest in the genetics of inflammatory skin disease and leads a series of large-scale studies to understand the biological mechanisms through which genetic variation influences psoriasis and acne.

Michael originally trained as a pharmacologist and subsequently studied Human Molecular Genetics at Imperial College before undertaking his PhD at St George’s University of London. His doctoral research was focused on the resolution of the genetic basis of recessive disorders present at elevated frequency in Old Order Amish populations. In 2009 Michael moved to King’s College London where his research capitalised on advances in DNA sequencing technologies to identify the genetic basis of a series of rare diseases that had proved intractable to traditional gene mapping approaches.

Between 2014 and 2021 Michael was head of Human Genetics at Genomics plc overseeing the development of the technology platform for target discovery and polygenic risk profiling. He continues to be actively involved in developing the analytical approaches needed to deploy contemporary genomic technologies at scale in healthcare systems and is currently head of Research and Innovation for the South East England NHS Genomic Medicine Service Alliance.

Abstract of the talk

The association of genetic variation with disease phenotypes provides a robust scientific platform to identify causal biological processes. Our recent large-scale studies have defined the genetic variation that explains a substantial proportion of the genetic risk of inflammatory skin disease and formed the substrate to identify the molecular mechanisms of disease, the cell-types in which they occur and the optimal targets for intervention.

Our genetic studies have supported the development of new therapies, targeting TYK2 and IL36, and defined genetic variation that influences therapeutic response in psoriasis. We have also established the causal role of specific molecular processes in the development of acne, identified putative therapeutic targets and demonstrated the relationship between genetic risk and disease severity.

Professor of Systems Ecology

Paul Wilmes

Paul Wilmes is Professor of Systems Ecology and holds appointments at the Luxembourg Centre for Systems Biomedicine and in the Department of Life Sciences and Medicine within the Faculty of Science, Technology and Medicine of the University of Luxembourg. He heads the Systems Ecology Research Group. During the COVID-19 pandemic, Paul acted as co-speaker of the COVID-19 Task Force of Research Luxembourg and was appointed “chargé de mission” by the University of Luxembourg. As a British Chevening Scholar, Paul earned his PhD from the School of Environmental Sciences at the University of East Anglia (UK). For part of his doctoral research, he spent time as a German Academic Exchange Service Visiting Scientist at the Max Planck Institute for Marine Microbiology in Bremen (Germany). Paul subsequently carried out postdoctoral research at the University of California, Berkeley (USA) from where he returned in 2010 to his native Luxembourg through the ATTRACT fellowship scheme of the Luxembourg National Research Fund. Paul was awarded an European Research Council (ERC) Consolidator Grant in 2019. He is an elected full member of the Institut Grand-Ducal, Section des Sciences naturelles, physiques et mathématiques, and the Académie Lorraine des Sciences. In 2018, Paul was awarded the Grand Prix in Biological Sciences of the Institut Grand-Ducal. Paul has authored more than 120 peer-review publications and is a Highly Cited Researcher. He is a frequently invited speaker at international scientific symposia and academic institutions.

Abstract of the talk

The human microbiome represents a complex ecosystem which, through its emergent properties, contributes essential functions to its host. Using integrated multi-omics in combination with high-throughput experimental systems, we are now starting to unravel these functions in the context of human health and disease. These insights will pave the way for revolutionary prognostic, diagnostic and therapeutic approaches.

Head of the Center of Neurology

Toomas Toomsoo

Toomas has studied in Germany and the USA. In Germany, at the Hertie Institute of the University of Tübingen, under Prof. Daniela Berg supervision, where started the evaluation of transcranial ultrasound examinations. Today, there are a number of new projects in this field with universities in Germany, Finland and Italy.

Abstract of the talk

Polygenic risk score for Parkinson’s disease and probability of substantia nigra hyperechogenicity in “healthy” adults

Several studies have investigated the association of the PD PRS with several aspects of well-established PD. By means of transcranial sonography (TCS), a larger area of increased echogenicity (hyperechogenicity) in substantia nigra (SN) has been found in patients with different neurodegenerative diseases, especially in PD compared to controls. This SN+ is thought to reflect increased iron deposits. Although its exact meaning remains unknown, it has been proposed to be a marker of SN degeneration or vulnerability. We sought to evaluate the association of PRS with the SN+in normal population who have high and low Parkinson’s disease PRS. An influential role for polygenic inheritance in PD is strongly supported by a number of studies, that revealed a significant association between disease risk, age of onset, motor progression, and cognitive decline with PRS, calculated from GWAS summary statistics for PD.However, all studies published today, examined the association of PRS with several aspects of well-established PD. There are no studies that investigate the association of this score with the probability of SN+ and its risk markers.

Associate Professor

Ulf van Orom

Ulf Andersson Vang Ørom is an Associate Professor at the Institute for Molecular Biology and Genetics at Aarhus University, Denmark. The laboratory’s interests focus on RNA biology, non-coding RNA, RNA modifications and splicing. Their approaches are centered on next-generation sequencing, molecular biology techniques and bioinformatics.

Abstract of the talk

m6A RNA modifications, splicing and cancer

Splicing efficiency varies among transcripts, and tight control of splicing kinetics is crucial for coordinated gene expression. N-6-methyladenosine (m6A) is the most abundant RNA modification and is involved in regulation of RNA biogenesis and function.

In our work we show that early m6A deposition specifies the fate of transcripts regarding splicing kinetics and alternative splicing. m6A deposition near splice junctions promotes fast splicing, while m6A modifications in introns are associated with long, slowly processed introns and alternative splicing events.

Several components of the molecular machinery regulating m6A deposition and removal have been shown to be involved in cancer. We have studied m6A methylation events in breast cancer cells using Direct RNA Sequencing that are directly affecting splicing and molecular function in disease to understand the molecular mechanism of m6A in cancer and to evaluate the potential of m6A-mediated mis-splicing as a therapeutic target in cancer.

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