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medRxiv

EPIC4ND: European Prospective Investigation into Cancer and Nutrition follow-up for neurodegenerative diseases

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  • January 29, 2025
  • Elio Riboli, et al., Imperial College London
Topic/Product:
CNS Disease Panel 120, Neurology
Disease Area:
Population Health
Sample Type:

Abstract

The ‘European Prospective Investigation into Cancer and Nutrition’ cohort (EPIC-Europe) is a prospective study including ∼520,000 participants recruited across Europe (1991-2000) with in-depth baseline data on nutritional, lifestyle, medical, and anthropometric variables, and baseline blood samples. Here we introduce EPIC4ND, a case-cohort study within EPIC designed to identify biomarkers predicting a future onset of dementia, Alzheimer’s disease (AD), Parkinson’s disease (PD), and amyotrophic lateral sclerosis (ALS).

EPIC4ND comprises 6,346 initially non-diseased participants (aged 35-80 years, mean age at baseline: 54±9, 65% women) with up to 30 years of follow-up and data on at least one omics domain available from pre-disease blood samples. EPIC4ND includes 4,604 subcohort members (4,447 non-cases and 157 incident cases) and 1,742 additional incident cases ascertained from the broader EPIC cohort. Among the incident cases, there are 1,190 dementia cases (818 AD), 534 PD cases, and 199 ALS cases. Additionally, 72 prevalent PD cases and 118 incident Parkinsonism cases are available for comparison. Molecular data generated encompass proteomics, genome-wide DNA methylation, and SNP genotyping with 4,065 EPIC4ND participants (2,497 non-cases, 1,568 incident cases) having data on all three domains. Smaller studies include data on metals, metabolites, and environmental chemicals, while ongoing efforts focus on ultrasensitive targeted biomarker measurements and small RNA sequencing.

Genome-wide association studies and analyses of epidemiological risk factors validate the dataset by confirming many known risk factors. Leveraging these extensive pre-disease multi-layered omics data offers a unique opportunity to identify biomarker signatures predicting neurodegenerative diseases and to explore their interplay with epidemiological risk factors.

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Authors & Affiliations

Christina M. Lill1,2, *, # , Jan Homann1, *, Olena Ohlei1 , Karl Smith-Byrne3 , Vivian Viallon4 , Jose Maria Huerta5,6 , Fanny Artaud7 , Yujia Zhao8 , Abigail Britten9 , Laura Deecke1 , Valerija Dobricic10 , Olatz Mokoroa11,12 , Marcela Guevara13,14,15 , Dafina Petrova16,17,18 , Miles Trupp19 , Jara Sabin20,21 , Mareike Gröninger20 , Sandra M. Colorado-Yohar5,6,22 , Sonia Alonso-Martin23 , Natalia CabreraCastro5,6 , Sergiu Groppa24 , Oliver Robinson2,25 , Johnni Hansen26 , Sture Eriksson†27 , Sabina Sieri28 , Ana Jimenez29,30 , Tammy Y. N. Tong3 , Rudolph Kaaks20 , Gianluca Severi7,31 , Ruth Travis3 , Nick Wareham9 , Andréa L. Benedet32,32 , Henrik Zetterberg32,33,34,35,36,37 , Andre Franke38 , Alexis Elbaz7 , Lars Bertram10 , Roel Vermeulen8,39 , Lefkos Middleton2 , Giovanna Masala40 , Carlotta Sacerdote41 , Susan Peters8 , Verena Katzke20 , Pietro Ferrari4 , Marc J. Gunter25,$ , Elio Riboli25,$

  1. 1. Institute of Epidemiology and Social Medicine, University of Münster, Münster, Germany
  2. Ageing and Epidemiology Unit (AGE), School of Public Health, Imperial College London, London, UK
  3. Cancer Epidemiology Unit, Nuffield Department of Population Health, University of Oxford, Oxford, UK
  4. International Agency for Research on Cancer (IARC/WHO), Nutrition and Metabolism Branch, 69366, Lyon, France
  5. Department of Epidemiology, Murcia Regional Health Council-IMIB, Murcia, Spain
  6. CIBER Epidemiología y Salud Pública (CIBERESP), Madrid, Spain
  7. Université Paris-Saclay, UVSQ, Inserm, Gustave Roussy, CESP, Villejuif, France
  8. Institute for Risk Assessment Sciences, Utrecht University, Utrecht, The Netherlands
  9. Medical Research Council Epidemiology Unit, University of Cambridge, Cambridge, UK
  10. Lübeck Interdisciplinary Platform for Genome Analytics (LIGA), University of Lübeck, Lübeck, Germany
  11. Epidemiology and Public Health Area, Biodonostia Health Research Institute, San Sebastián, Spain
  12. Sub-Directorate for Public Health and Addictions of Gipuzkoa, Ministry of Health of the Basque Government, San Sebastián, Spain
  13. Instituto de Salud Pública y Laboral de Navarra, Pamplona, Spain
  14. Centro de Investigación Biomédica en Red de Epidemiología y Salud Pública (CIBERESP), Madrid, Spain
  15. Navarra Institute for Health Research (IdiSNA), Pamplona, Spain
  16. Escuela Andaluza de Salud Pública (EASP), Granada, Spain
  17. Instituto de Investigación Biosanitaria ibs.GRANADA, Granada, Spain
  18. Centro de Investigación Biomédica en Red de Epidemiología y Salud Pública (CIBERESP), Madrid, Spain
  19. Department of Clinical Sciences, Neurosciences, Umeå University, Umeå, Sweden
  20. Division of Cancer Epidemiology, German Cancer Research Center, Heidelberg, Germany
  21. 1st Medical Clinic, University Hospital Mannheim, Mannheim, Germany
  22. 9 enero Research Group on Demography and Health, National Faculty of Public Health, University of Antioquia, Medellin, Colombia
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Steve Williams, MD, PhD

CSO

Dr. Willams serves as the company’s Chief Scientific Officer. He was previously Chief Medical Officer at Standard Biotools and at SomaLogic where he pioneered the discipline for discovery and validation of predictive, diagnostic and prognostic models using machine-learning applied to large-plex proteomics. 20 such tests were used for drug characterization, safety and efficacy when incorporated in clinical drug trials at Pharma/Biotech and 17 different multivariate tests were validated and translated into regulated healthcare uses. Prior to SomaLogic, Dr. Williams was at Pfizer in the UK and the USA as a clinical triallist in Translational Medicine, and subsequently as VP, Global Clinical Technology. He sat on the National Advisory Council for the National Institute of Biomedical Imaging and Bioengineering, the Executive Committee for the FNIH Biomarkers Consortium, and worked with FDA and PhRMA on developing evidentiary standards for biomarker qualification. Dr. William’s medical training was in London, at Charing Cross and Westminster Medical School, followed by a PhD in medicine/physiology at the same institution and training in Radiology at the University of Newcastle Upon Tyne. Steve is co-inventor on 26 proteomics patents and author/coauthor on multiple foundational proteomics manuscripts.

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Justin McAnear

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Mr. McAnear serves as the company’s Chief Financial Officer. He brings over 25 years of operational and financial leadership experience across various sectors and was instrumental in taking 10x Genomics public in 2019, serving as its CFO for over five years. Mr. McAnear served for over 3 years as Tesla’s VP of Worldwide Finance and Operations, supporting landmark initiatives such as the Model X and Model 3 launches and Solar City acquisition.  He also held various roles at Apple and J&J earlier in his career and served as a naval officer and aviator for over 9 years.