Integration of questionnaire-based risk factors improves polygenic risk scores for human coronary heart disease and type 2 diabetes

Disease areas:

heart and blood vessels
nutrition and metabolism

Last updated:: 2 July 2025

Author(s):: Aarno Palotie, Mark Daly, Bridget Riley-Gills, Howard Jacob, Dirk Paul, Heiko Runz, Sally John, Robert Plenge, Joseph Maranville, George Okafo, Nathan Lawless, Heli Salminen-Mankonen, Mark McCarthy, Julie Hunkapiller, Meg Ehm, Kirsi Auro, Simonne Longerich, Caroline Fox, Anders Mälarstig, Katherine Klinger, Deepak Raipal, Eric Green, Robert Graham, Robert Yang, Chris O'Donnell, Tomi Mäkelä, Jaakko Kaprio, Petri Virolainen, Antti Hakanen, Terhi Kilpi, Markus Perola, Jukka Partanen, Anne Pitkäranta, Juhani Junttila, Raisa Serpi, Tarja Laitinen, Veli-Matti Kosma, Arto Mannermaa, Jari Laukkanen, Marco Hautalahti, Outi Tuovila, Raimo Pakkanen, Jeffrey Waring, Ioanna Tachmazidou, Chia-Yen Chen, Shameek Biswas, Zhihao Ding, Marc Jung, Rion Pendergrass, David Pulford, Neha Raghavan, Adriana Huertas-Vazquez, Jae-Hoon Sul, Xinli Hu, Sahar Mozaffari, Dawn Waterworth, Nicole Renaud, Ma´en Obeidat, Samuli Ripatti, Johanna Schleutker, Mikko Arvas, Olli Carpén, Reetta Hinttala, Johannes Kettunen, Katriina Aalto-Setälä, Mika Kähönen, Johanna Mäkelä, Reetta Kälviäinen, Valtteri Julkunen, Hilkka Soininen, Anne Remes, Mikko Hiltunen, Jukka Peltola, Pentti Tienari, Juha Rinne, Roosa Kallionpää, Ali Abbasi, Adam Ziemann, Sahar Esmaeeli, Nizar Smaoui, Anne Lehtonen, Susan Eaton, Sanni Lahdenperä, Janet van Adelsberg, Natalie Bowers, Edmond Teng, Sarah Pendergrass, Onuralp Soylemez, Kari Linden, Fanli Xu, Laura Addis, John Eicher, Minna Raivio, Beryl Cummings, Juulia Partanen, Martti Färkkilä, Jukka Koskela, Sampsa Pikkarainen, Airi Jussila, Katri Kaukinen, Timo Blomster, Mikko Kiviniemi, Markku Voutilainen, Graham Heap, Fedik Rahimov, Keith Usiskin, Tim Lu, Danny Oh, Kirsi Kalpala, Melissa Miller, Linda McCarthy, Kari Eklund, Antti Palomäki, Pia Isomäki, Laura Pirilä, Oili Kaipiainen-Seppänen, Johanna Huhtakangas, Apinya Lertratanakul, David Close, Marla Hochfeld, Nan Bing, Jorge Esparza Gordillo, Tarja Laitinen, Margit Pelkonen, Paula Kauppi, Hannu Kankaanranta, Terttu Harju, Riitta Lahesmaa, Alex Mackay, Glenda Lassi, Steven Greenberg, Hubert Chen, Joanna Betts, Soumitra Ghosh, Rajashree Mishra, Sina Rüeger, Teemu Niiranen, Felix Vaura, Veikko Salomaa, Markus Juonala, Kaj Metsärinne, Mika Kähönen, Juhani Junttila, Markku Laakso, Jussi Pihlajamäki, Daniel Gordin, Juha Sinisalo, Marja-Riitta Taskinen, Tiinamaija Tuomi, Jari Laukkanen, Benjamin Challis, Jaakko Parkkinen, Russell Miller, Audrey Chu, Amanda Elliott, Joel Rämö, Mary Pat Reeve, Sanni Ruotsalainen, Tuomo Meretoja, Heikki Joensuu, Olli Carpén, Lauri Aaltonen, Johanna Mattson, Annika Auranen, Peeter Karihtala, Saila Kauppila, Päivi Auvinen, Klaus Elenius, Johanna Schleutker, Relja Popovic, Bridget Riley-Gillis, Jennifer Schutzman, Andrey Loboda, Aparna Chhibber, Heli Lehtonen, Stefan McDonough, Marika Crohns, Sauli Vuoti, Diptee Kulkarni, Esa Pitkänen, Kai Kaarniranta, Joni A. Turunen, Terhi Ollila, Sanna Seitsonen, Hannu Uusitalo, Vesa Aaltonen, Hannele Uusitalo-Järvinen, Marja Luodonpää, Nina Hautala, Mengzhen Liu, Stephanie Loomis, Erich Strauss, Hao Chen, Anna Podgornaia, Juha Karjalainen, Kaisa Tasanen, Laura Huilaja, Katariina Hannula-Jouppi, Teea Salmi, Sirkku Peltonen, Leena Koulu, Ying Wu, David Choy, Pirkko Pussinen, Aino Salminen, Tuula Salo, David Rice, Pekka Nieminen, Ulla Palotie, Maria Siponen, Liisa Suominen, Päivi Mäntylä, Ulvi Gursoy, Vuokko Anttonen, Kirsi Sipilä, Hannele Laivuori, Venla Kurra, Oskari Heikinheimo, Ilkka Kalliala, Laura Kotaniemi-Talonen, Kari Nieminen, Päivi Polo, Kaarin Mäkikallio, Eeva Ekholm, Marja Vääräsmäki, Outi Uimari, Laure Morin-Papunen, Marjo Tuppurainen, Katja Kivinen, Elisabeth Widén, Taru Tukiainen, Liu Aoxing, Eija Laakkonen, Niko Välimäki, Johannes Kettunen, Mikko Arvas, Janet Kumar, Andrea Ganna, Justin Wade Davis, Danjuma Quarless, Slavé Petrovski, Eleonor Wigmore, Adele Mitchell, Benjamin Sun, Ellen Tsai, Denis Baird, Paola Bronson, Ruoyu Tian, Yunfeng Huang, Elmutaz Mohammed, Samir Wadhawan, Erika Kvikstad, Minal Caliskan, Diana Chang, Tushar Bhangale, Kirill Shkura, Victor Neduva, Xing Chen, Åsa Hedman, Karen S. King, Padhraig Gormley, Jimmy Liu, Clarence Wang, Ethan Xu, Franck Auge, Clement Chatelain, Deepak Rajpal, Dongyu Liu, Katherine Call, Tai-He Xia, Matt Brauer, Huilei Xu, Amy Cole, Jonathan Chung, Jaison Jacob, Katrina de Lange, Jonas Zierer, Mitja Kurki, Aki Havulinna, Juha Mehtonen, Priit Palta, Shabbeer Hassan, Pietro Della Briotta Parolo, Wei Zhou, Mutaamba Maasha, Susanna Lemmelä, Manuel Rivas, Arto Lehisto, Vincent Llorens, Mari E. Niemi, Henrike Heyne, Kimmo Palin, Javier Garcia-Tabuenca, Harri Siirtola, Tuomo Kiiskinen, Jiwoo Lee, Kristin Tsuo, Kati Kristiansson, Kati Hyvärinen, Jarmo Ritari, Miika Koskinen, Katri Pylkäs, Marita Kalaoja, Minna Karjalainen, Tuomo Mantere, Eeva Kangasniemi, Sami Heikkinen, Samuel Heron, Dhanaprakash Jambulingam, Venkat Subramaniam Rathinakannan, Nina Pitkänen, Perttu Terho, Sirpa Soini, Eero Punkka, Sanna Siltanen, Teijo Kuopio, Anu Jalanko, Huei-Yi Shen, Risto Kajanne, Mervi Aavikko, Masahiro Kanai, L. Elisa Lahtela, Mari Kaunisto, Elina Kilpeläinen, Timo P. Sipilä, Oluwaseun Alexander Dada, Awaisa Ghazal, Anastasia Kytölä, Kati Donner, Timo P. Sipilä, Anu Loukola, Päivi Laiho, Tuuli Sistonen, Essi Kaiharju, Markku Laukkanen, Elina Järvensivu, Sini Lähteenmäki, Lotta Männikkö, Regis Wong, Minna Brunfeldt, Sami Koskelainen, Tero Hiekkalinna, Teemu Paajanen, Kalle Pärn, Shuang Luo, Vishal Sinha, Mary Pat Reeve, Harri Siirtola, Javier Gracia-Tabuenca, Mika Helminen, Tiina Luukkaala, Iida Vähätalo, Jyrki Pitkänen, Mirkka Koivusalo, Sarah Smith, Tom Southerington
Publish date:: 23 February 2022
Journal:: Communications Biology
PubMed ID:: 35197564
DOI:: 10.1038/s42003-021-02996-0

Abstract

Large-scale biobank initiatives and commercial repositories store genomic data collected from millions of individuals, and tools to leverage the rapidly growing pool of health and genomic data in disease prevention are needed. Here, we describe the derivation and validation of genomics-enhanced risk tools for two common cardiometabolic diseases, coronary heart disease and type 2 diabetes. Data used for our analyses include the FinnGen study (N = 309,154) and the UK Biobank project (N = 343,672). The risk tools integrate contemporary genome-wide polygenic risk scores with simple questionnaire-based risk factors, including demographic, lifestyle, medication, and comorbidity data, enabling risk calculation across resources where genome data is available. Compared to routinely used clinical risk scores for coronary heart disease and type 2 diabetes prevention, the risk tools show at least equivalent risk discrimination, improved risk reclassification (overall net reclassification improvements ranging from 3.7 [95% CI 2.8-4.6] up to 6.2 [4.6-7.8]), and capacity to be improved even further with standard lipid and blood pressure measurements. Without the need for blood tests or evaluation by a health professional, the risk tools provide a powerful yet simple method for preliminary cardiometabolic risk assessment for individuals with genome data available.