Integration of questionnaire-based risk factors improves polygenic risk scores for human coronary heart disease and type 2 diabetes
Authors: Tamlander Max , Mars Nina , Pirinen Matti ,   FinnGen,   Steering Committee, Palotie Aarno , Daly Mark ,   Pharmaceutical companies, Riley-Gills Bridget , Jacob Howard , Paul Dirk , Runz Heiko , John Sally , Plenge Robert , Maranville Joseph , Okafo George , Lawless Nathan , Salminen-Mankonen Heli , McCarthy Mark , Hunkapiller Julie , Ehm Meg , Auro Kirsi , Longerich Simonne , Fox Caroline , Mälarstig Anders , Klinger Katherine , Raipal Deepak , Green Eric , Graham Robert , Yang Robert , O’Donnell Chris ,   University of Helsinki & Biobanks, Mäkelä Tomi , Kaprio Jaakko , Virolainen Petri , Hakanen Antti , Kilpi Terhi , Perola Markus , Partanen Jukka , Pitkäranta Anne , Junttila Juhani , Serpi Raisa , Laitinen Tarja , Kosma Veli-Matti , Mannermaa Arto , Laukkanen Jari , Hautalahti Marco ,   Other Experts/Non-Voting Members, Tuovila Outi , Pakkanen Raimo ,   Scientific Committee,   Pharmaceutical companies, Waring Jeffrey , Tachmazidou Ioanna , Chen Chia-Yen , Biswas Shameek , Ding Zhihao , Jung Marc , Pendergrass Rion , Pulford David , Raghavan Neha , Huertas-Vazquez Adriana , Sul Jae-Hoon , Hu Xinli , Mozaffari Sahar , Waterworth Dawn , Renaud Nicole , Obeidat Ma´en ,   University of Helsinki & Biobanks, Ripatti Samuli , Schleutker Johanna , Arvas Mikko , Carpén Olli , Hinttala Reetta , Kettunen Johannes , Aalto-Setälä Katriina , Kähönen Mika , Mäkelä Johanna ,   Clinical Groups,   Neurology Group, Kälviäinen Reetta , Julkunen Valtteri , Soininen Hilkka , Remes Anne , Hiltunen Mikko , Peltola Jukka , Tienari Pentti , Rinne Juha , Kallionpää Roosa , Abbasi Ali , Ziemann Adam , Esmaeeli Sahar , Smaoui Nizar , Lehtonen Anne , Eaton Susan , Lahdenperä Sanni , van Adelsberg Janet , Bowers Natalie , Teng Edmond , Pendergrass Sarah , Soylemez Onuralp , Linden Kari , Xu Fanli , Addis Laura , Eicher John , Raivio Minna , Cummings Beryl , Partanen Juulia ,   Gastroenterology Group, Färkkilä Martti , Koskela Jukka , Pikkarainen Sampsa , Jussila Airi , Kaukinen Katri , Blomster Timo , Kiviniemi Mikko , Voutilainen Markku , Heap Graham , Rahimov Fedik , Usiskin Keith , Lu Tim , Oh Danny , Kalpala Kirsi , Miller Melissa , McCarthy Linda ,   Rheumatology Group, Eklund Kari , Palomäki Antti , Isomäki Pia , Pirilä Laura , Kaipiainen-Seppänen Oili , Huhtakangas Johanna , Lertratanakul Apinya , Close David , Hochfeld Marla , Bing Nan , Gordillo Jorge Esparza ,   Pulmonology Group, Laitinen Tarja , Pelkonen Margit , Kauppi Paula , Kankaanranta Hannu , Harju Terttu , Lahesmaa Riitta , Mackay Alex , Lassi Glenda , Greenberg Steven , Chen Hubert , Betts Joanna , Ghosh Soumitra , Mishra Rajashree , Rüeger Sina ,   Cardiometabolic Diseases Group, Niiranen Teemu , Vaura Felix , Salomaa Veikko , Juonala Markus , Metsärinne Kaj , Kähönen Mika , Junttila Juhani , Laakso Markku , Pihlajamäki Jussi , Gordin Daniel , Sinisalo Juha , Taskinen Marja-Riitta , Tuomi Tiinamaija , Laukkanen Jari , Challis Benjamin , Parkkinen Jaakko , Miller Russell , Chu Audrey , Elliott Amanda , Rämö Joel , Reeve Mary Pat , Ruotsalainen Sanni ,   Oncology Group, Meretoja Tuomo , Joensuu Heikki , Carpén Olli , Aaltonen Lauri , Mattson Johanna , Auranen Annika , Karihtala Peeter , Kauppila Saila , Auvinen Päivi , Elenius Klaus , Schleutker Johanna , Popovic Relja , Riley-Gillis Bridget , Schutzman Jennifer , Loboda Andrey , Chhibber Aparna , Lehtonen Heli , McDonough Stefan , Crohns Marika , Vuoti Sauli , Kulkarni Diptee , Pitkänen Esa ,   Opthalmology Group, Kaarniranta Kai , Turunen Joni A. , Ollila Terhi , Seitsonen Sanna , Uusitalo Hannu , Aaltonen Vesa , Uusitalo-Järvinen Hannele , Luodonpää Marja , Hautala Nina , Liu Mengzhen , Loomis Stephanie , Strauss Erich , Chen Hao , Podgornaia Anna , Karjalainen Juha ,   Dermatology Group, Tasanen Kaisa , Huilaja Laura , Hannula-Jouppi Katariina , Salmi Teea , Peltonen Sirkku , Koulu Leena , Wu Ying , Choy David ,   Odontology Group, Pussinen Pirkko , Salminen Aino , Salo Tuula , Rice David , Nieminen Pekka , Palotie Ulla , Siponen Maria , Suominen Liisa , Mäntylä Päivi , Gursoy Ulvi , Anttonen Vuokko , Sipilä Kirsi ,   Women’s Health and Reproduction Group, Laivuori Hannele , Kurra Venla , Heikinheimo Oskari , Kalliala Ilkka , Kotaniemi-Talonen Laura , Nieminen Kari , Polo Päivi , Mäkikallio Kaarin , Ekholm Eeva , Vääräsmäki Marja , Uimari Outi , Morin-Papunen Laure , Tuppurainen Marjo , Kivinen Katja , Widén Elisabeth , Tukiainen Taru , Aoxing Liu , Laakkonen Eija , Välimäki Niko , Kettunen Johannes , Arvas Mikko , Kumar Janet , Ganna Andrea ,   FinnGen Analysis working group, Davis Justin Wade , Quarless Danjuma , Petrovski Slavé , Wigmore Eleonor , Mitchell Adele , Sun Benjamin , Tsai Ellen , Baird Denis , Bronson Paola , Tian Ruoyu , Huang Yunfeng , Mohammed Elmutaz , Wadhawan Samir , Kvikstad Erika , Caliskan Minal , Chang Diana , Bhangale Tushar , Shkura Kirill , Neduva Victor , Chen Xing , Hedman Åsa , King Karen S. , Gormley Padhraig , Liu Jimmy , Wang Clarence , Xu Ethan , Auge Franck , Chatelain Clement , Rajpal Deepak , Liu Dongyu , Call Katherine , Xia Tai-He , Brauer Matt , Xu Huilei , Cole Amy , Chung Jonathan , Jacob Jaison , de Lange Katrina , Zierer Jonas , Kurki Mitja , Havulinna Aki , Mehtonen Juha , Palta Priit , Hassan Shabbeer , Della Briotta Parolo Pietro , Zhou Wei , Maasha Mutaamba , Lemmelä Susanna , Rivas Manuel , Lehisto Arto , Llorens Vincent , Niemi Mari E. , Heyne Henrike , Palin Kimmo , Garcia-Tabuenca Javier , Siirtola Harri , Kiiskinen Tuomo , Lee Jiwoo , Tsuo Kristin , Kristiansson Kati , Hyvärinen Kati , Ritari Jarmo , Koskinen Miika , Pylkäs Katri , Kalaoja Marita , Karjalainen Minna , Mantere Tuomo , Kangasniemi Eeva , Heikkinen Sami , Heron Samuel , Jambulingam Dhanaprakash , Rathinakannan Venkat Subramaniam , Pitkänen Nina ,   Biobank directors, Terho Perttu , Soini Sirpa , Punkka Eero , Siltanen Sanna , Kuopio Teijo ,   FinnGen Teams,   Administration, Jalanko Anu , Shen Huei-Yi , Kajanne Risto , Aavikko Mervi ,   Analysis, Kanai Masahiro ,   Clinical Endpoint Development, Lahtela L. Elisa ,   Communication, Kaunisto Mari ,   E-Science, Kilpeläinen Elina , Sipilä Timo P. , Dada Oluwaseun Alexander , Ghazal Awaisa , Kytölä Anastasia ,   Genotyping, Donner Kati , Sipilä Timo P. ,   Sample Collection Coordination, Loukola Anu ,   Sample Logistics, Laiho Päivi , Sistonen Tuuli , Kaiharju Essi , Laukkanen Markku , Järvensivu Elina , Lähteenmäki Sini , Männikkö Lotta , Wong Regis ,   Registry Data Operations, Brunfeldt Minna , Koskelainen Sami , Hiekkalinna Tero , Paajanen Teemu ,   Sequencing Informatics, Pärn Kalle , Luo Shuang , Sinha Vishal ,   Trajectory, Reeve Mary Pat , Siirtola Harri , Gracia-Tabuenca Javier , Helminen Mika , Luukkaala Tiina , Vähätalo Iida ,   Data protection officer, Pitkänen Jyrki ,   FinBB - Finnish biobank cooperative, Koivusalo Mirkka , Smith Sarah , Southerington Tom , Widén Elisabeth , Ripatti Samuli 
Published: February 2022

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.