INTERVENE
News and Events
Some of the things we have been up to
Free Webinar on calculating PGS with the PGS calculator on Dec 4, 2024
EMB-EBI are organising a webinar to demonstrate how to use scoring files from the PGS Catalog (or custom files) to calculate PGS in your own samples using the PGS Catalog Calculator (pgsc_calc). The pgsc_calc software reproducibly automates PGS calculation in commonly used genotyping formats (plink, VCF) alongside capabilities for adjusting PGS in the context of genetic ancestry (necessary for proper interpretation of PGS across diverse populations). This webinar introduces the software and describes the ancestry adjustment process included in the Calculator, along with information about how to run the tool and interpret results.
This webinar is suitable for researchers, clinicians and bioinformaticians working in the field of human genomics. Experience using command line interface (CLI) applications on Linux or macOS is highly recommended but not essential.
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Register here:
Calculating polygenic scores with the Polygenic Score Catalog Calculator | EMBL-EBI Training
September 27, 2024
Updates to the Polygenic Score Catalog, including data from multi-ancestry or non-European populations, and the PGS Catalog calculator have now been published in Nature Genetics paper
July 27, 2024
The PGS Catalog Calculator has been installed at diverse biobanks and trusted research environments
INTERVENE supports the development of the Polygenic Score (PGS) Catalog Calculator, which reproducibly calculates PGS, conducts genetic similarity analysis, and adjusts calculated scores in the context of genetic ancestry.
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The Calculator includes automatic genetic ancestry similarity analysis using population reference panels. PGSs can be normalized across genetic ancestry similarity groups making it particularly useful for working on multiple biobanks to analyse diverse cohorts in a systematic way. Currently many PGS have ancestry biases and transferability problems. INTERVENE is using the adjusted calculator scores to investigate PGS effects on cumulative disease incidence in a diverse cohort including over 1 million global biobank participants. The Calculator is portable, meaning analysts can bring "code to the data" on any platform without transferring sensitive data. It supports offline environments and is scalable to population biobanks. Extensive documentation, a GitHub issue tracker, and a community forum support users.
So far, the Calculator has been deployed to over 10 global biobanks, including HUNT, Genes & Health, China Kadoorie Biobank, and All of Us. Read more about the PGS Catalog Calculator.
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June 12, 2024
The flagship paper has docked at Nature Communications
INTERVENE proudly presents our flagship paper that describes the new framework we developed for estimating cumulative disease incidences over the life course. We considered country-specific differences in disease incidence as well as how risk estimation of polygenic scores (PGS) varies by both age and sex. We integrated PGS associations from seven studies in four countries (N=1,197,129) with disease incidences from the Global Burden of Disease and found that PGSs had a significant sex-specific effect on asthma, hip osteoarthritis, gout, coronary heart disease and type 2 diabetes with all but type 2 diabetes exhibiting a larger effect in men than women. The effect of PGS was larger in younger individuals for 13 of 18 diseases studied with the effects decreasing linearly with age. The data we used came from biobank studies including FinnGen, UK Biobank, Genomics England, Trøndelag Health Study, Generation Scotland, Estonian Biobank and Mass General Brigham Biobank.
Our framework allows stratification for risk-based prevention and screening using PGS accounting for country, age and sex for 18 high-burden diseases. By appropriately accounting for age and sex-specific PGS effects, our easily extendable framework increases the generalizability of results from biobank studies and the accuracy of absolute risk estimates. We demonstrate the importance and utility of PGS: by making PGS comparable to other risk factors, we provide a tool for public health officials to make informed decisions on how to use PGS in real-world settings.
The study, which was a multi-centered effort led by INTERVENE coordinators Andrea Ganna and Samuli Ripatti, is now published in Nature Communications.
One of the three first authors, Brooke Wolford, sees the impact of the work as two-fold: “Firstly, we provide a framework for estimating one's lifetime risk of disease based on age, sex, country, and polygenic burden of disease which should facilitate conversations between patients and physicians with numbers that are a bit easier to comprehend than the relative risks that are often used. Secondly, we demonstrate how these more accurate risk estimates might change screening and surveillance programs to deliver on the promise of precision medicine.”
Professor Samuli Ripatti continues: Our study highlights the power of combining 1.2 million biobanked samples across Europe. This allowed us for the first time to show that in many diseases the effects of polygenic risk scores are much higher in young individuals compared to older participants and some effects are also different for males and females. These observations may have implications when implementing the risk scores to clinical practice.
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Jermy, Läll, Wolford et al. Nature Communications June 12, 2024
A unified framework for estimating country-specific cumulative incidence for 18 diseases stratified by polygenic risk
May 3, 2024
INTERVENE featured in the We're doomed, we're saved podcast
INTERVENE researchers Brooke Wolford and Kristi Läll joined hosts Andreas Horchler and Louise von Stechow in the latest episode of the biorevolution podcast We're, doomed We're saved to talk about polygenic risk scores.
Check out the discussion:
Apple:
https://podcasts.apple.com/de/podcast/we-are-doomed-we-are-saved-22/id1638090318?i=1000654391391
Spotify:
https://open.spotify.com/episode/4gOIgDvLz8NB2yUrf3Hiqi?si=3Q4iZEtQTHq_m8wuRIj3yA
Youtube:
https://www.youtube.com/watch?v=_eImY2_NODE
February 9, 2024
Helen Cooper (UH) has started as the new Communications Officer for INTERVENE.
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We are also anticipating the arrival of our flagship paper. Watch this space!
News in the New Year
December 7, 2023
INTERVENE goes Copenhagen
Members from INTERVENE attended a workshop “Future of Predictive Genomics in Denmark”, sponsored by Thermo Fisher Scientific and Allelica, to take part in a discussion on the state of predictive genomics in the Nordics. INTERVENE's Andrea Ganna held the keynote on PRS in Nordics and Europe today, presenting the project and its key achievements, as well as participated in a panel discussion on the present status and future prospects of PRS. Many thanks to the organizers for having us!
October 11-12, 2023
Annual Meeting in Rotterdam
It’s that time of year again! This October, INTERVENErs came together for a consortium-wide Annual Meeting in beautiful and unusually warm Rotterdam. The meeting was hosted by INTERVENE partner ttopstart – for which many thanks for ensuring a productive, hospitable, well-organized event encompassing great science, good food in the beautiful Netherlands.
The event featured scientific presentations from across the consortium and work packages, small-group planning sessions and interactive workshops. To interface with similar initiatives for inspiration and possible collaborative synergies, the meeting began with a session featuring external talks within the larger theme of clinical utility of polygenic risk scores. Following insightful presentations from Francesco Florindi (Thermo Fisher), Sowmiya Moorthie (PHG Foundation), and Suzette Delaloge (Gustave Roussy), INTERVENEs Elisabeth Widén moderated a panel discussion focusing on whether and when polygenic risk scores are ripe for the clinic.
Following several excellent research updates from across INTERVENE, we convened for an afternoon workshop to discuss a key priority for the consortium - the joint effort on embedded ethics. We rounded off the day with a working dinner and networking event.
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The following day was focused on strategy, with the morning session dedicated to plans for the second half of the project. Following presentations and discussions on the project’s business plan and infrastructure platform, we departed Rotterdam with renewed and reinforced excitement toward our joint effort as well as fresh ideas, connections, and perspectives.
Our warmest thanks to all speakers, participants, and organizers of this intense, productive and well-executed event. We hope to see you all soon again!
INTERVENE coordinator Andrea Ganna recaps the achievements for the first half of the project
Sunny faces under cloudy skies in Rotterdam
September 21, 2023
Project review - past the midway point
At the turn of summer, INTERVENE reached its midway point. We have now reached 30 months of project activities, with 30 more months to go until the project ends in December 2025.
In connection with our half-way mark, the project was subjected to a periodic review by European Commission staff and external reviewers. During an intense full-day meeting in September, the project leadership presented the main achievements as well as forward-looking activities and directions for the latter half of the project. As part of the review, INTERVENE prepared a comprehensive periodic report, which together with project deliverables and financial statements was scrutinized by our reviewers.
In its evaluation report, the Reviewers commended the project for its leadership and its continued excellent performance in scientific output. It was noted that the overall project progress is good and convincing, that work foreseen for the period has been performed according to the original plan with all planned deliverables and milestones successfully achieved.
The review issued 10 recommendations for the consortium to consider, which we will incorporate into our strategy for the latter half if the project. As before, presentations were clear and well prepared, and we are pleased that the dialogue with the reviewers was positive and constructive throughout the intense day.
Many thanks to all INTERVENErs for making our first half a very successful one!
June 21, 2023
Paper spotlight: The flagship has left the harbor
Polygenic scores offer the ability to predict genetic risk for complex disease across the life course. To produce risk estimates relevant for clinical and public health decision making, it is important to account for any varying effects due to common risk factors such as age and sex. In a flagship paper from INTERVENE, we report the development of a novel framework to estimate for cumulative incidences over the life course. Using data on more than 1.3M individuals, we provide a PRS-based framework for country-, age-, and sex-specific estimates of the cumulative incidence for 18 high-burden diseases. Our easily extendable framework increases the generalizability of results from biobank studies and the accuracy of absolute risk estimates by appropriately accounting age and sex-specific PGS effects. Our paperhighlight the potential of PGS as a screening tool which may assist in the early prevention of common disease.
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The preprint for "A unified framework for estimating country-specific cumulative incidence for 18 diseases stratified by polygenic risk" is available at: https://www.medrxiv.org/content/10.1101/2023.06.12.23291186v1
April 13-14, 2023
INTERVENE analyst workshop in Siena
Analysts from across the project met up for a two-day workshop in beautiful vernal Siena, Italy to discuss the status and future plans of the project. The meeting took place at the University of Siena’s Historical Aula Magna with plenty of visual inspiration for highflying ideation.
The first day of the workshop was dedicated to alignment and discussion on the current status of ongoing and planned work. Following opening words from INTERVENE coordinator Andrea Ganna, project groups gave presentations on the status, opportunities and possible challenges in the project. This was followed short teaser presentations from partner biobanks for a discussion of new data modalities available at each INTERVENE biobank.
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The second day of the workshop was devoted to the planning of upcoming work, task allocation, and work on analyses or deliverables. The day started with group discussions on machine learning for epidemiology & improving PRS and biomarker trajectories & utilizing available omics data. The workshop concluded with a one-hour session for presenting the outline of the upcoming scientific papers from INTERVENE.
This was a very inspiring workshop that helped form many new and great ideas. Thank you to all presenters, discussion leaders, and other participants!
March 7, 2023
INTERVENE featured in German newspaper Tagesspiegel
Today, INTERVENE was featured in German newspaper Tagesspiegel, with Henrike Heyne and Christoph Lipper of Hasso Plattner Institute commenting on INTERVENE and the possibilities to improve predictions of the individual disease risk and progression by application of AI-based technologies to a large pool of genomic and health data.
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December 24, 2022
Merry Christmas and A Successful 2023!
As the year 2022 is on its final stretches, we want to wish all INTERVENErs, collaborators, and other stakeholders Happy Holidays and a happy new year 2023!
December 1, 2022
Polygenic risk scores or family information? Why not both?
How do polygenic risk scores complement family history information? A recent paper from INTERVENE researchers leverages family relationships, 50 years of nationwide registries, and genome-wide genotyping seeks to find out by examining the interplay of family history and genome-wide polygenic risk scores across 24 common diseases. The article shows that family history and PRS are independent and not interchangeable measures, but instead provide complementary information on inherited disease susceptibility. The PRSs explained on average 10% of the effect of first-degree family history, and first-degree family history 3% of PRSs, and PRS effects were independent of both early- and late-onset family history. The PRS stratified the risk similarly in individuals with and without family history. In most diseases, including coronary artery disease, glaucoma, and type 2 diabetes, a positive family history with a high PRS was associated with a considerably elevated risk, whereas a low PRS compensated completely for the risk implied by positive family history. This study provides a catalogue of risk estimates for both family history of disease and PRSs and highlights opportunities for a more comprehensive way of assessing inherited disease risk across common diseases.
November 4, 2022
INTERVENE featured in the ASHG Thought Leadership Series
A new INTERVENE video is out on our YouTube channel. In connection with the Annual Meeting 2022, we hosted a film crew to sit down with our research leaders and talented analysts to talk about the mission of INTERVENE, and the potential for polygenic risk scores in informing better health care decisions going forward. Check out the video below!
November 3, 2022
INTERVENE moves forward with RCT on risk awareness effects on health behaviour
The first of two clinical pilot programmes assessing the impact of genetic disease risk awareness on health behaviour and decision support has now been registered at ClinicalTrials.gov. Led by Mikk Jürisson from the University of Tartu, the registered study will explore to what extent awareness of high polygenic risk for cardiovascular disese (CVD) can influence changes in health behavior among young overweight adults in Estonia.
Another forthcoming study, carried out in Helsinki, Turin, and Siena, will evaluate the impact of polygenic risk information for decision support and primary prevention of breast cancer.
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The Estonian study will enroll more than 1,500 overweight young adults (ages 25-44) with high either high or low genetic risk for CVD. The trial will be conducted in a primary care setting, for which the high genetic-risk subjects will be invited to visit their family physician. In the course of the first visit, the family physician will assess the participant's health status and will counsel the participant on healthy choices for increasing their level of physical activity and losing weight. If necessary, the physician will start treatment to lower the participant's blood pressure or cholesterol following current treatment guidelines. The participants in the intervention group will be informed of their high polygenic risk for CVD at the start of the study, while the control subjects at the end of the study. There will be three study visits at 6-month intervals. Between visits, the participants will receive reminders via a mobile health application to change their health behavior. At the end of the trial (month 12), the health indicators of the participants will be assessed and compared between the three trial groups. If a significant difference in BMI is found, it will presumably be related to the fact of learning of the high genetic risk, in which case the use of genetic data in primary prevention may be considered effective.
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Read more about the trial here
October 25-29, 2022
Strong visibility for INTERVENE at the ASHG 2022 meeting
The Annual Meeting of the American Society of Human Genetics is held in Los Angeles, CA on October 25-29, 2022.
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We are very proud to announce that no less than four talks at the ASHG will be coming from the INTERVENE project:
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Brooke Wolford (Norwegian University of Science and Technology): Variability in lifetime risk of 20 complex diseases across European countries and polygenic score strata in over 1 million individuals
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Julian Wanner (Hasso Plattner Institute): Potential clinical utility of PRS in disease prognosis. The glass is half full
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Bradley Jermy (Institute for Molecular Medicine Finland, University of Helsinki): Testing for interaction using >1 million individuals and 20 diseases shows considerable differences in PRS estimates across age groups and sexes
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Nina Mars (Institute for Molecular Medicine Finland, University of Helsinki): Can genetic associations for disease onset be used to predict disease prognosis? The glass is half empty
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In addition, Brooke has been selected as a postdoctoral finalist for the prestigious Charles J. Epstein Trainee Awards for Excellence in Human Genetics Research. We wish Brooke and the other speakers best of luck for their talks.
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Finally, the meeting will also serve as the premier for the short video feature of INTERVENE in the ASHG 2022 Thought Leadership Film Series. To check out the video, click here!
October 12-13, 2022
INTERVENE Annual Meeting 2022
Following nearly two years of Covid-19 imposed travel and meeting restrictions, INTERVENE finally convened for its first consortium-wide, in-person Annual Meeting at Hilton Helsinki Kalastajatorppa for a two day meeting to enjoy excellent science, good food, and the magnificent splendor of Finnish Autumn. In all, approximately 60 INTERVENE members attended the meeting in person, including the INTERVENE Scientific Advisory Board Members, Profs. Cathryn Lewis, Jacques Fellay, and Jukka Corander.
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The event featured scientific presentations from across the consortium and work packages, small-group planning sessions and interactive workshops. The keynote was delivered by Saskia Sanderson, Chief Medical Scientist at Our Future Health, presenting the new UK-based national health research cohort for early detection and prevention research and approaches for returning polygenic risk scores results to study participants. We thank Saskia for her excellent talk and valuable lessons learned from the Our Future Health project.
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As we departed on October 13, it was with a renewed and reinforced enthusiasm with new ideas, connections, and perspectives in our carry-on. Our warmest thanks to all speakers, participants, and organizers of this intense, productive and well-executed event. We hope to see you all soon again!
All smiles at the INTERVENE Annual Meeting group photo.
September 10-12, 2022
Two Nature journal papers to start off September
Fall is here, and we are excited to announce two recent papers from the INTERVENE consortium:
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In a Nature Medicine article, Sakari Jukarainen and colleagues from the Institute for Molecular Medicine Finland, University of Helsinki, ask the question to what extent genetic risk factors impact overall disease burden. The study combines genetic and disease outcome information with data on healthy life years measured by disability-adjusted life years to estimate the effect of genetic variants on the risk of developing 80 major diseases. The results show that genetic risk factors account for a sizable number of healthy life years lost, both at the individual and population level. Given that genetic risk factors seem to have a substantial impact on healthy life years, the framework will help to inform the development and implementation of genetic-based clinical applications.
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For more information, see the article Genetic risk factors have a substantial impact on healthy life years and a separate commentary by the lead authors.
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In a paper in Nature Communications, Remo Monti and colleagues from the Hasso Plattner Institute present an improved tool for genetic variant effect prediction to aid discovery and interpretation of genetic associations for rare variants. Using exome sequencing data from 200,000 individuals, the authors compare different gene-based association test across 193 significant gene-biomarker associations, and introduce a new and statistically powerful combination of tests that found 36% more associations than standard implementations. The work will facilitate discovery and interpretation of genetic associations for rare variant diseases, and facilitate the development of new and improved risk scores for INTERVENE.
For more information, see Identifying interpretable gene-biomarker associations with functionally informed kernel-based tests in 190,000 exomes.
June 11-14, 2022
INTERVENE at ESHG 2022
The Annual Meeting of the European Society for Human Genetics was held in hybrid format in Vienna, Austria on June 11-14, 2022.
INTERVENE was strongly represented during the meeting, presenting posters and talks on ongoing work covering the application of polygenic scores for risk assessment and disease progression, as well as a new powerful approach for synthetic data generation.
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Many thanks to our presenters:
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Sophie Wharrie (Aalto University): A fast method to generate hundreds of thousands of synthetic genomes and phenotypes (poster)
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Brooke Wolford (Norwegian University of Science and Technology): Effect of sex and age on disease prediction with polygenic scores in INTERVENE
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Julian Wanner (Hasso Plattner Institute): Polygenic risk scores for disease progression in clinically related events
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Bradley Jermy (Institute for Molecular Medicine Finland, University of Helsinki): INTERVENE: exploring the generalizability of polygenic risk scores on disease
June 11, 2022
INTERVENE's Andrea Ganna awarded the 2022 Leena Peltonen Prize
We are happy and proud to announce that Andrea Ganna, FIMM-EMBL group leader and co-coordinator of INTERVENE, has received this year's Leena Peltonen prize at the ESHG annual meeting Vienna. Many congratulations, Andrea!
April 13-14, 2022
Berlin workshop
After nearly two years of COVID-imposed remote work, INTERVENE analysts finally got together for a face-to-face meeting from 13-14 April 2022 in Berlin, Germany. A group of international analysts and representatives from organisations in the project attended the two-day workshop.
February 16, 2022
A review of year 1
In early 2022, INTERVENE underwent a comprehensive scheduled evaluation by the European Commission to examine all project activities so far.
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November 3, 2021
INTERVENE Annual Meeting
On November 2, 2021 we held the first INTERVENE Annual Meeting, uniting the entire INTERVENE consortium for a collegial day of discussion of performed and ongoing work, and to plan the execution of forward steps. Due to COVID-19 restrictions, the meeting was held virtually.
September 13, 2021
INTERVENE Newsletter
Check out the first newsletter from INTERVENE
June 9, 2021
Ranking the risk of heart disease
Samuli Ripatti appeared in the Nature Outlook discussing his work to identify individuals at high risk of coronary heart disease
February 9, 2021
INTERVENE featured on Genomeweb
News piece on INTERVENE on Genomeweb
January 18, 2021
INTERVENE launched!
We are all set to go! Check out the press release on the launch of INTERVENE