Expansion Areas

FinnGen 2 Expansion Areas (EAs): 

• EA1 -  Enhancing the recruitment of specific clinical areas
• EA2 - Recontacting participants with questionnaires
• EA3 - Expanding the phenotype information with clinical data
• EA4 - Supporting means to replicate FinnGen association results 
• EA5 - Blood analysis pipeline for follow-up functional studies and Clinical and Molecular Characterization of Finnish enriched alleles
• EA6 - Cognitive decline in prodromal Alzheimer’s  

Expansion Area 1 (EA1): Enhancing the recruitment of specific clinical areas 

This initiative focused on bolstering the collection of biobank samples in clinical areas that were underrepresented in FinnGen. Additional resources, such as research nurses, were allocated to biobanks to support the enhanced collection. From the autumn of 2020 to the spring of 2023, six hospital biobanks in Finland received support from FinnGen to recruit a nurse. The Helsinki Biobank also received assistance with a second nurse to enhance oncology collection. 

The FinnGen Steering Committee endorsed the enhanced recruiting efforts, which primarily targeted the clinical areas of neurology, rheumatology, interstitial lung disease (ILD), heart failure, oncology (Helsinki Biobank) and gastroenterology. 

Expansion Area 2 (EA2): Recontacting participants with questionnaires

Expansion Area 2 (EA2) aimed to enhance FinnGen data by reaching out to participants with questionnaires. The goal was to gather additional health and lifestyle information not available in national registers.

The plan was to contact 6,000 FinnGen participants through an online portal and achieve a participation rate of over 50% with a questionnaire completion rate of over 75%. The study was to be conducted in phases: starting with a pilot study of 6,000 participants, then scaling up to 20,000, and finally to 200,000 participants.

The pilot study, launched successfully in February 2021, involved three clinical biobanks and the development of an online portal called OmaBiopankki (OwnBiobank). While the portal improved contacting participants, it was deemed insufficient for large-scale implementation. Administrative processes also needed streamlining.

After assessing the feasibility and work plans for scaling up, the Steering Committee decided to discontinue the EA2 activities. Resources were reallocated to support core goals instead. The study protocol has been published in BMJ Open (https://pubmed.ncbi.nlm.nih.gov/36198465/). 

Expansion Area 3 (EA3): Expanding the phenotype information with clinical data

Many complex diseases have different disease trajectories and underlying causes. The life-long healthcare data available in national health registers provide a strong tool to tackle the problem of disease progression. However, not all data relevant to health and welfare are available through national registers. Such data include eg. quantitative measures, like biomarkers (laboratory values, physiological measures, symptoms, hospital administered drugs, tumour pathology data; or disease-specific composite phenotypes). To improve the quality of disease trajectory studies, altogether 8 EA3 studies were conducted during FinnGen 2 that aimed to acquire additional clinical data relevant to phenotype validation and patient stratification.

 FinnGen 2 EA3 studies: 

• Fatty liver disease (FLD) 
• Age-related macular degeneration (AMD)
• Women's health (subprojects: PCOS, Endometriosis and Cervical dysplasia) 
• Diabetes and rare kidney diseases 
• Oncology (subprojects: Breast, Prostate and Ovarian cancer) 
• Pulmonology 
• Immune-mediated diseases (subprojects Rheumatic diseases and IBD) 
• Heart failure 

EA4 - supporting means to replicate FinnGen association results 

EA4 aimed to standardise and conduct meta-analyses of disease endpoints across FinnGen, UK Biobank (with up to 500,000 study subjects), and the Estonian Biobank (with up to 200,000 study subjects).

Within this initiative, the FinnGen core analysis team conducted a meta-analysis of 873 corresponding endpoints (matched based on ICD-10 definitions) from the pan-UK Biobank study, focusing on a European subset of this dataset. The results of this analysis are publicly available at (link to access results).

Additionally, FinnGen established a research collaboration with the Estonian Biobank, harmonising a total of 607 FinnGen endpoints within their database. Subsequently, the FinnGen core analysis team performed a three-way meta-analysis, combining GWAS results from 415 matching endpoints across FinnGen, the Estonian Biobank, and the pan-UK Biobank study. The research collaboration with the Estonian Biobank ended at the end of FinnGen 2. 

EA5 - Blood analysis pipeline for follow-up functional studies and clinical and molecular characterization of Finnish enriched alleles

The EA5 project aimed to establish a streamlined process for collecting and analyzing blood samples from 2500 Finnish blood donors already included in the FinnGen project. Specifically, the focus was on examining around 100 genetic variations associated with diseases, which are more prevalent in the Finnish population.

The project had two main phases:

1. Initially, the goal was to develop and refine a process for collecting plasma, serum, and peripheral blood samples from 500 FinnGen-genotyped donors, demonstrating the feasibility of the collection method.
2. Subsequently, the same collection process was scaled up to include samples from an additional 2000 donors.

The pilot phase successfully showed that samples could be collected, stored, and transported to the biobank within a short time frame of two to four hours, ensuring high-quality samples for subsequent analysis. By August 2023, a total of 2500 samples had been successfully collected, primarily from donation sites in the Helsinki area.

To better understand the functional implications of the 100 disease-associated genetic variants specific to the Finnish population, various analyses were performed on the collected samples:

• Metabolomics data was generated from approximately 1000 plasma samples using the Metabolon platform.
• Proteomics data was obtained from around 2200 plasma samples using the Olink 3K platform, and from approximately 1000 plasma samples using the SomaLogic platform.
• Serum samples (around 2200) were analysed for clinical chemistry and full blood cell counts.
• Peripheral blood mononuclear cells (PBMCs) from approximately 360 donors underwent single-nucleus RNA and ATAC sequencing, as well as immunophenotyping. Additionally, single cell painting was performed on approximately 400 PBMCs.

EA6 - Cognitive decline in prodromal Alzheimer’s  

This pilot activity focused on recalling older biobank participants to investigate the utility of easily implementable methods for assessing the risk of Alzheimer’s disease (AD). A better understanding of the earliest stages of AD could expedite the development or administration of treatments. The pilot utilised unique Finnish legacy cohorts that allowed the assessment of longitudinal changes in cognition and plasma biomarkers in conjunction with genetic risk scores for AD. The project also compared various computer and tablet-based software measuring memory and functional ability to neuropsychological examinations carried out by health care professionals.

First, a Proof of Concept study was conducted at the University of Eastern Finland (UEF) Brain Research Unit, with 140 study subjects invited for both onsite and remote cognitive tests. This was the first FinnGen sub-project to invite participants for further clinical examinations. Data collection and study visits were conducted in early 2022 and the results of the pilot study were published in 2023. Altogether 27 study subjects were successfully recalled and completed the study.  

A larger multi-center study (TWINGEN) was launched in 2023 and by the end of the year, 950 study subjects were recruited, of which approximately 700 completed the tests. The analysis of the results is underway, and several novel publications based on the collected data are in preparation. The TWINGEN study protocol is described in a preprint format here.