A1 Refereed original research article in a scientific journal
FinnGen provides genetic insights from a well-phenotyped isolated population
Authors: Kurki Mitja I., Karjalainen Juha, Palta Priit, Sipilä Timo P., Kristiansson Kati, Donner Kati M., Reeve Mary P., Laivuori Hannele, Aavikko Mervi, Kaunisto Mari A., Loukola Anu, Lahtela Elisa, Mattsson Hannele, Laiho Päivi, Parolo Pietro Della Briotta, Lehisto Arto A., Kanai Masahiro, Mars Nina, Rämö Joel, Kiiskinen Tuomo, Heyne Henrike O., Veerapen Kumar, Rüeger Sina, Lemmelä Susanna, Zhou Wei, Ruotsalainen Sanni, Pärn Kalle, Hiekkalinna Tero, Koskelainen Sami, Paajanen Teemu, Llorens Vincent, Gracia-Tabuenca Javier, Siirtola Harri, Reis Kadri, Elnahas Abdelrahman G., Sun Benjamin, Foley Christopher N., Aalto-Setälä Katriina, Alasoo Kaur, Arvas Mikko, Auro Kirsi, Biswas Shameek, Bizaki-Vallaskangas Argyro, Carpen Olli, Chen Chia-Yen, Dada Oluwaseun A., Ding Zhihao, Ehm Margaret G., Eklund Kari, Färkkilä Martti, Finucane Hilary, Ganna Andrea, Ghazal Awaisa, Graham Robert R., Green Eric M., Hakanen Antti, Hautalahti Marco, Hedman Åsa K., Hiltunen Mikko, Hinttala Reetta, Hovatta Iiris, Hu Xinli, Huertas-Vazquez Adriana, Huilaja Laura, Hunkapiller Julie, Jacob Howard, Jensen Jan-Nygaard, Joensuu Heikki, John Sally, Julkunen Valtteri, Jung Marc, Junttila Juhani, Kaarniranta Kai, Kähönen Mika, Kajanne Risto, Kallio Lila, Kälviäinen Reetta, Kaprio Jaakko, FinnGen, Kerimov Nurlan, Kettunen Johannes, Kilpeläinen Elina, Kilpi Terhi, Klinger Katherine, Kosma Veli-Matti, Kuopio Teijo, Kurra Venla, Laisk Triin, Laukkanen Jari, Lawless Nathan, Liu Aoxing, Longerich Simonne, Mägi Reedik, Mäkelä Johanna, Mäkitie Antti, Malarstig Anders, Mannermaa Arto, Maranville Joseph, Matakidou Athena, Meretoja Tuomo, Mozaffari Sahar V., Niemi Mari E. K., Niemi Marianna, Niiranen Teemu, O´Donnell Christopher J., Obeidat Ma´en, Okafo George, Ollila Hanna M., Palomäki Antti, Palotie Tuula, Partanen Jukka, Paul Dirk S., Pelkonen Margit, Pendergrass Rion K., Petrovski Slavé, Pitkäranta Anne, Platt Adam, Pulford David, Punkka Eero, Pussinen Pirkko, Raghavan Neha, Rahimov Fedik, Rajpal Deepak, Renaud Nicole A., Riley-Gillis Bridget, Rodosthenous Rodosthenis, Saarentaus Elmo, Salminen Aino, Salminen Eveliina, Salomaa Veikko, Schleutker Johanna, Serpi Raisa, Shen Huei-yi, Siegel Richard, Silander Kaisa, Siltanen Sanna, Soini Sirpa, Soininen Hilkka, Sul Jae Hoon, Tachmazidou Ioanna, Tasanen Kaisa, Tienari Pentti, Toppila-Salmi Sanna, Tukiainen Taru, Tuomi Tiinamaija, Turunen Joni A., Ulirsch Jacob C., Vaura Felix, Virolainen Petri, Waring Jeffrey, Waterworth Dawn, Yang Robert, Nelis Mari, Reigo Anu, Metspalu Andres, Milani Lili, Esko Tõnu, Fox Caroline, Havulinna Aki S., Perola Markus, Ripatti Samuli, Jalanko Anu, Laitinen Tarja, Mäkelä Tomi P., Plenge Robert, McCarthy Mark, Runz Heiko, Daly Mark J., Palotie Aarno
Publisher: Nature Portfolio
Publication year: 2023
Journal: Nature
Journal name in source: NATURE
Journal acronym: NATURE
Volume: 613
Issue: 7944
First page : 508
Last page: 518
Number of pages: 20
ISSN: 0028-0836
eISSN: 1476-4687
DOI: https://doi.org/10.1038/s41586-022-05473-8
Web address : https://www.nature.com/articles/s41586-022-05473-8
Self-archived copy’s web address: https://research.utu.fi/converis/portal/detail/Publication/178868920
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 x 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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