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Cited by 4,233Genetic Associations and EpidemiologyGenomics and Rare DiseasesForensic and Genetic Research

FinnGen provides genetic insights from a well-phenotyped isolated population

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Kurki, Mitja I., Karjalainen, Juha, Palta, Priit, Sipilä, Timo P., Kristiansson, Kati, Donner, Kati M., Reeve, Mary P., Laivuori, Hannele +161 more·2023·Nature
DOI 10.1038/s41586-022-05473-8PMC PMC9849126
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Abstract

Abstract Population isolates such as those in Finland benefit genetic research because deleterious alleles are often concentrated on a small number of low-frequency variants (0.1% ≤ minor allele frequency < 5%). These variants survived the founding bottleneck rather than being distributed over a large number of ultrarare variants. Although this effect is well established in Mendelian genetics, its value in common disease genetics is less explored 1,2 . FinnGen aims to study the genome and national health register data of 500,000 Finnish individuals. Given the relatively high median age of participants (63 years) and the substantial fraction of hospital-based recruitment, FinnGen is enriched for disease end points. Here we analyse data from 224,737 participants from FinnGen and study 15 diseases that have previously been investigated in large genome-wide association studies (GWASs). We also include meta-analyses of biobank data from Estonia and the United Kingdom. We identified 30 new associations, primarily low-frequency variants, enriched in the Finnish population. A GWAS of 1,932 diseases also identified 2,733 genome-wide significant associations (893 phenome-wide significant (PWS), P < 2.6 × 10 –11 ) at 2,496 (771 PWS) independent loci with 807 (247 PWS) end points. Among these, fine-mapping implicated 148 (73 PWS) coding variants associated with 83 (42 PWS) end points. Moreover, 91 (47 PWS) had an allele frequency of <5% in non-Finnish European individuals, of which 62 (32 PWS) were enriched by more than twofold in Finland. These findings demonstrate the power of bottlenecked populations to find entry points into the biology of common diseases through low-frequency, high impact variants.

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  • FinnGen is a biobank-scale cohort integrating genotype data from approximately 500,000 Finnish participants with longitudinal health information derived from national registries.

    “FinnGen is a biobank-scale cohort integrating genotype data from approximately 500,000 Finnish participants with longitudinal health information derived from national registries.”

    From Protective PLCG2 variants associate with a delayed onset of Alzheimer’s disease among heterozygous APOE ε4 carriers (2026) · cites this paper as [16]

    The Main section and Methods > Biobank samples confirm that FinnGen links genotype data from Finnish biobanks to longitudinal national health-register data. But the paper describes 500,000 participants as a goal, not the size of the genotyped cohort reported here: 412,000 samples had been collected and 224,737 participants were included in the study. (LLM, conf=0.91)

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References 64 · Cited by 4,233

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Authors
Kurki, M. I., Karjalainen, J., Palta, P., Sipilä, T. P., Kristiansson, K., Donner, K. M., Reeve, M. P., Laivuori, H., Aavikko, M., Kaunisto, M. A., Loukola, A., Lahtela, E., Mattsson, H., Laiho, P., Della Briotta Parolo, P., Lehisto, A. A., Kanai, M., Mars, N., Rämö, J., Kiiskinen, T., Heyne, H. O., Veerapen, K., Rüeger, S., Lemmelä, S., Zhou, W., Ruotsalainen, S., Pärn, K., Hiekkalinna, T., Koskelainen, S., Paajanen, T., Llorens, V., Gracia-Tabuenca, J., Siirtola, H., Reis, K., Elnahas, A. G., Sun, B., Foley, C. N., Aalto-Setälä, K., Alasoo, K., Arvas, M., Auro, K., Biswas, S., Bizaki-Vallaskangas, A., Carpen, O., Chen, C.-Y., Dada, O. A., Ding, Z., Ehm, M. G., Eklund, K., Färkkilä, M., Finucane, H., Ganna, A., Ghazal, A., Graham, R. R., Green, E. M., Hakanen, A., Hautalahti, M., Hedman, Å. K., Hiltunen, M., Hinttala, R., Hovatta, I., Hu, X., Huertas-Vazquez, A., Huilaja, L., Hunkapiller, J., Jacob, H., Jensen, J.-N., Joensuu, H., John, S., Julkunen, V., Jung, M., Junttila, J., Kaarniranta, K., Kähönen, M., Kajanne, R., Kallio, L., Kälviäinen, R., Kaprio, J., FinnGen, Kerimov, N., Kettunen, J., Kilpeläinen, E., Kilpi, T., Klinger, K., Kosma, V.-M., Kuopio, T., Kurra, V., Laisk, T., Laukkanen, J., Lawless, N., Liu, A., Longerich, S., Mägi, R., Mäkelä, J., Mäkitie, A., Malarstig, A., Mannermaa, A., Maranville, J., Matakidou, A., Meretoja, T., Mozaffari, S. V., Niemi, M. E. K., Niemi, M., Niiranen, T., O´Donnell, C. J., Obeidat, M., Okafo, G., Ollila, H. M., Palomäki, A., Palotie, T., Partanen, J., Paul, D. S., Pelkonen, M., Pendergrass, R. K., Petrovski, S., Pitkäranta, A., Platt, A., Pulford, D., Punkka, E., Pussinen, P., Raghavan, N., Rahimov, F., Rajpal, D., Renaud, N. A., Riley-Gillis, B., Rodosthenous, R., Saarentaus, E., Salminen, A., Salminen, E., Salomaa, V., Schleutker, J., Serpi, R., Shen, H.-Y., Siegel, R., Silander, K., Siltanen, S., Soini, S., Soininen, H., Sul, J. H., Tachmazidou, I., Tasanen, K., Tienari, P., Toppila-Salmi, S., Tukiainen, T., Tuomi, T., Turunen, J. A., Ulirsch, J. C., Vaura, F., Virolainen, P., Waring, J., Waterworth, D., Yang, R., Nelis, M., Reigo, A., Metspalu, A., Milani, L., Esko, T., Fox, C., Havulinna, A. S., Perola, M., Ripatti, S., Jalanko, A., Laitinen, T., Mäkelä, T. P., Plenge, R., McCarthy, M., Runz, H., Daly, M. J., & Palotie, A.
Affiliations
  • Broad Institute (US)
  • University of Helsinki (FI)
  • Finnish Institute for Health and Welfare (FI)
  • Tampere University (FI)
  • University of Tartu (EE)
  • Biogen (United States) (US)
  • University of Cambridge (GB)
  • Finnish Red Cross (FI)
  • Glaxosmithkline (Finland) (FI)
  • Bristol-Myers Squibb (United States) (US)
  • Tampere University Hospital (FI)
  • Boehringer Ingelheim (Germany) (DE)
  • GlaxoSmithKline (United States) (US)
  • Helsinki University Hospital (FI)
  • Maze (United States) (US)
  • University of Turku (FI)
  • Pfizer (United States) (US)
  • Oulu University Hospital (FI)
  • Genentech (US)
  • AbbVie (United States) (US)
  • University of Eastern Finland (FI)
  • Northern Ostrobothnia Hospital District (FI)
  • Merck & Co., Inc., Rahway, NJ, USA (United States) (US)
  • AstraZeneca (United Kingdom) (GB)
  • Janssen (Belgium) (BE)
Corresponding author
Palotie, Aarno
ORCID
Venue
Nature
Publisher
Springer Science and Business Media LLC
Published
2023-01-18
Volume
613
Issue
7944
Pages
508-518
ISSN
  • 0028-0836 (ISSN-L)
  • 1476-4687
DOI
10.1038/s41586-022-05473-8
PMC
PMC9849126
OpenAlex
W4317390883
Cited by
4,233
References
64
Citations by year
2026: 900 · 2025: 1498 · 2024: 1455 · 2023: 376 · 2022: 1 · 2016: 1
FWCI
721.84
Type
journal article
Language
en
Update notices
correction (2023-02-24)
Open access
Licence
Locations
  • Nature (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • Apollo (University of Cambridge) (submittedVersion, cc-by)
  • RePEc: Research Papers in Economics (submittedVersion)
  • Työväentutkimus Vuosikirja (submittedVersion)
  • Tampere University Institutional Repository (Tampere University) (submittedVersion, cc-by)
  • STM:n Hallinnonalan avoin julkaisuarkisto (Julkari) (submittedVersion)
  • Apollo
  • Apollo (cc-by)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genomics and Rare Diseases
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Forensic and Genetic Research
Keywords
FinnGen, isolated populations, founder effect, low-frequency variants, phenome-wide association study, fine mapping, disease loci, Finnish population
MeSH terms
Disease, Estonia, Finland, Gene Frequency, United Kingdom, Humans, Middle Aged, Phenotype, Meta-Analysis as Topic, Genetic Predisposition to Disease, White People, Genome-Wide Association Study

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