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

Authors: Max Tamlander, Nina Mars, Matti Pirinen, FinnGen, Aarno Palotie, Mark J. Daly, Pharmaceutical companies, Bridget Riley-Gills, Howard J. Jacob, Dirk S. Paul, Heiko Runz, Sally John, Robert M. Plenge, Joseph Maranville, George Okafo, Nathan Lawless, Heli Salminen‐Mankonen, Mark I. McCarthy, Julie Hunkapiller, Meg Ehm, Kirsi Auro, Simonne Longerich, Caroline S. Fox, Anders Mälarstig, Katherine Klinger, Deepak Raipal, Eric Green, Robert Graham, Robert Yang, Chris O’Donnell, Tomi P. 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, Other Experts/Non-Voting Members, Outi Tuovila, Raimo Pakkanen, Pharmaceutical companies, Jeffrey Waring, Ioanna Tachmazidou, Chia-Yen Chen, Shameek Biswas, Zhihao Ding, Marc Jung, Rion Pendergrass, David Pulford, Neha Raghavan, Adriana Huertas‐Vázquez, Jae-Hoon Sul, Xinli Hu, Sahar V. 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, Neurology Group, Reetta Kälviäinen, Valtteri Julkunen, Hilkka Soininen, Anne M. Remes, Mikko Hiltunen, Jukka Peltola, Pentti J. Tienari, Juha O. 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 A. Pendergrass, Onuralp Söylemez, Kari Linden, Fanli Xu, Laura Addis, John D. Eicher, Minna Raivio, Beryl B. Cummings, Juulia Partanen, Gastroenterology Group, Martti Färkkilâ, 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, Rheumatology Group, Kari K. Eklund, Antti Palomäki, Pia Isomäki, Laura Pirilä, Oili Kaipiainen‐Seppänen, Johanna Huhtakangas, Apinya Lertratanakul, David A. Close, Marla Hochfeld, Nan Bing, Jorge Esparza Gordillo, Pulmonology Group, Tarja Laitinen, Margit Pelkonen, Paula Kauppi, Hannu Kankaanranta, Terttu Harju, Riitta Lahesmaa, Alex Mackay, Glenda Lassi, Steven M. Greenberg, Hubert Chen, Joanna Betts, Soumitra Ghosh, Rajashree Mishra, Sina Rüeger, Cardiometabolic Diseases Group, 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 Y. Chu, Amanda Elliott, Joel Rämö, Mary Pat Reeve, Sanni Ruotsalainen, Oncology Group, Tuomo J Meretoja, Heikki Joensuu, Olli Carpén, Lauri A. Aaltonen, Johanna Mattson, Annika Auranen, Peeter Karihtala, Saila Kauppila, Päivi Auvinen, Klaus Elenius, Johanna Schleutker, Relja Popovic, Bridget Riley-Gillis, Jennifer L. Schutzman, Andrey Loboda, Aparna Chhibber, Heli Lehtonen, Stefan McDonough, Marika Crohns, Sauli Vuoti, Diptee Kulkarni, Esa Pitkänen, Opthalmology Group, 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 C. Strauss, Hao Chen, Anna Podgornaia, Juha Karjalainen, Dermatology Group, Kaisa Tasanen, Laura Huilaja, Katariina Hannula‐Jouppi, Teea Salmi, Sirkku Peltonen, Leena Koulu, Ying Wu, David F. Choy, Odontology Group, Pirkko J. Pussinen, Aino Salminen, Tuula Salo, David Rice, Pekka Nieminen, Ulla Palotie, Maria Siponen, Liisa Suominen, Päivi Mäntylä, Ulvi Kahraman Gürsoy, Vuokko Anttonen, Kirsi Sipilä, Women’s Health and Reproduction Group, 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 K. Laakkonen, Niko Välimäki, Johannes Kettunen, Mikko Arvas, Janet Kumar, Andrea Ganna, FinnGen Analysis working group, J. Wade Davis, Danjuma Quarless, Slavé Petrovski, Eleonor Wigmore, Adele A. Mitchell, Benjamin B. Sun, Ellen Tsai, Denis Baird, Paola G. Bronson, Ruoyu Tian, Yunfeng Huang, Elmutaz Shaikho Elhaj Mohammed, Samir Wadhawan, Erika Kvikstad, Minal Çalışkan, Diana Chang, Tushar Bhangale, Kirill Shkura, Victor Neduva, Xing Chen, Åsa K. Hedman, Karen S. King, Padhraig Gormley, Jimmy Liu, Clarence Wang, Ethan Xu, Franck Augé, Clément Chatelain, Deepak K. Rajpal, Dongyu Liu, Katherine M. Call, Tai-he Xia, Matt Brauer, Huilei Xu, Amy L. Cole, Jonathan Chung, Jaison Jacob, Katrina de Lange, Jonas Zierer, Mitja Kurki, Aki S. Havulinna, Juha Mehtonen, Priit Palta, Shabbeer Hassan, Pietro Della Briotta Parolo, Wei Zhou, Mutaamba Maasha, Susanna Lemmelä, Manuel A. Rivas, Arto Lehistö, Vincent Llorens, Mari Niemi, Henrike Heyne, Kimmo Palin, Javier Gracia‐Tabuenca, Harri Siirtola, Tuomo Kiiskinen, Jiwoo Lee, Kristin Tsuo, Kati Kristiansson, Kati Hyvärinen, Jarmo Ritari, Miika Koskinen, Katri Pylkäs, Marita Kalaoja, Minna K. Karjalainen, Tuomo Mantere, Eeva Kangasniemi, Sami Heikkinen, Samuel Heron, Dhanaprakash Jambulingam, Venkat Subramaniam Rathinakannan, Nina Pitkänen, Biobank directors, Perttu Terho, Sirpa Soini, Eero Punkka, Sanna Siltanen, Teijo Kuopio, FinnGen Teams, Administration, Anu Jalanko, Huei-Yi Shen, Risto Kajanne, Mervi Aavikko, Analysis, Masahiro Kanai, L. Elisa Lahtela, Communication, Mari Kaunisto, E-Science, Elina Kilpeläinen, Timo P. Sipilä, Oluwaseun Alexander Dada, Awaisa Ghazal, Anastasia Kytölä, Genotyping, Kati Donner, Timo P. Sipilä, Sample Collection Coordination, Anu Loukola, Sample Logistics, Päivi Laiho, Tuuli Sistonen, Essi Kaiharju, Markku Laukkanen, Elina Järvensivu, Sini Lähteenmäki, Lotta Männikkö, Regis Wong, Registry Data Operations, Minna Brunfeldt, Sami Koskelainen, Tero Hiekkalinna, Teemu Paajanen, Sequencing Informatics, Kalle Pärn, Shuang Luo, Vishal Sinha, Trajectory, Mary Pat Reeve, Harri Siirtola, Javier Gracia‐Tabuenca, Mika Helminen, Tiina Luukkaala, Iida Vähätalo, Data protection officer, Jyrki Pitkänen, FinBB - Finnish biobank cooperative, Mirkka Koivusalo, Sarah Smith, Tom Southerington, Elisabeth Widén, Samuli Ripatti - Communications Biology 2022 cited by 51

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.