Sex-specific genetic risks for adverse outcomes after coronary revascularization procedures
Author:
Nurkkala Jouko Marko12ORCID, Aittokallio Jenni12ORCID, Palotie Aarno, Daly Mark, Riley-Gills Bridget, Jacob Howard, Paul Dirk, Matakidou Athena, Platt Adam, Runz Heiko, John Sally, Okafo George, Lawless Nathan, Salminen-Mankonen Heli, Plenge Robert, Maranville Joseph, McCarthy Mark, Hunkapiller Julie, Ehm Margaret G, Auro Kirsi, Longerich Simonne, Fox Caroline, Mälarstig Anders, Klinger Katherine, Raipal Deepak, Green Eric, Graham Robert, Yang Robert, ÓDonnell Chris, Mäkelä Tomi P, Kaprio Jaakko, Virolainen Petri, Hakanen Antti, Kilpi Terhi, Perola Markus, Partanen Jukka, Pitkäranta Anne, Raivio Taneli, Serpi Raisa, Laitinen Tarja, Kosma Veli-Matti, Laukkanen Jari, Hautalahti Marco, Tuovila Outi, Pakkanen Raimo, Waring Jeffrey, Riley-Gillis Bridget, Rahimov Fedik, Tachmazidou Ioanna, Chen Chia-Yen, Runz Heiko, Ding Zhihao, Jung Marc, Biswas Shameek, Pendergrass Rion, Hunkapiller Julie, Ehm Margaret G, Pulford David, Raghavan Neha, Huertas-Vazquez Adriana, Sul Jae-Hoon, Mälarstig Anders, Hu Xinli, Klinger Katherine, Graham Robert, Green Eric, Mozaffari Sahar, Waterworth Dawn, Renaud Nicole, Obeidat Máen, Ripatti Samuli, Schleutker Johanna, Perola Markus, Arvas Mikko, Carpén Olli, Hinttala Reetta, Kettunen Johannes, Mannermaa Arto, Aalto-Setälä Katriina, Kähönen Mika, Laukkanen Jari, Mäkelä Johanna, Kälviäinen Reetta, Julkunen Valtteri, Soininen Hilkka, Remes Anne, Hiltunen Mikko, Peltola Jukka, Raivio Minna, Tienari Pentti, Rinne Juha, Kallionpää Roosa, Partanen Juulia, Abbasi Ali, Ziemann Adam, Smaoui Nizar, Lehtonen Anne, Eaton Susan, Runz Heiko, Lahdenperä Sanni, Biswas Shameek, Hunkapiller Julie, Bowers Natalie, Teng Edmond, Pendergrass Rion, Xu Fanli, Pulford David, Auro Kirsi, Addis Laura, Eicher John, Li Qingqin S, He Karen, Khramtsova Ekaterina, Raghavan Neha, Färkkilä Martti, Koskela Jukka, Pikkarainen Sampsa, Jussila Airi, Kaukinen Katri, Blomster Timo, Kiviniemi Mikko, Voutilainen Markku, Daly Mark, Abbasi Ali, Waring Jeffrey, Smaoui Nizar, Rahimov Fedik, Lehtonen Anne, Lu Tim, Bowers Natalie, Pendergrass Rion, McCarthy Linda, Hart Amy, Guan Meijian, Miller Jason, Kalpala Kirsi, Miller Melissa, Hu Xinli, Eklund Kari, Palomäki Antti, Isomäki Pia, Pirilä Laura, Kaipiainen-Seppänen Oili, Huhtakangas Johanna, Mars Nina, Abbasi Ali, Waring Jeffrey, Rahimov Fedik, Lertratanakul Apinya, Smaoui Nizar, Lehtonen Anne, Hochfeld Marla, Bowers Natalie, Pendergrass Rion, Gordillo Jorge Esparza, Auro Kirsi, Waterworth Dawn, Farias Fabiana, Kalpala Kirsi, Bing Nan, Hu Xinli, Laitinen Tarja, Pelkonen Margit, Kauppi Paula, Kankaanranta Hannu, Harju Terttu, Lahesmaa Riitta, Smaoui Nizar, Lassi Glenda, Eaton Susan, Chen Hubert, Pendergrass Rion, Bowers Natalie, Betts Joanna, Auro Kirsi, Mishra Rajashree, Mouded Majd, Ngo Debby, Niiranen Teemu, Vaura Felix, Salomaa Veikko, Metsärinne Kaj, Aittokallio Jenni, Kähönen Mika, Hernesniemi Jussi, Gordin Daniel, Sinisalo Juha, Taskinen Marja-Riitta, Tuomi Tiinamaija, Hiltunen Timo, Laukkanen Jari, Elliott Amanda, Reeve Mary Pat, Ruotsalainen Sanni, Challis Benjamin, Paul Dirk, Hunkapiller Julie, Bowers Natalie, Pendergrass Rion, Chu Audrey, Auro Kirsi, Reilly Dermot, Mendelson Mike, Parkkinen Jaakko, Miller Melissa, Meretoja Tuomo, Joensuu Heikki, Carpén Olli, Mattson Johanna, Salminen Eveliina, Auranen Annika, Karihtala Peeter, Auvinen Päivi, Elenius Klaus, Schleutker Johanna, Pitkänen Esa, Mars Nina, Daly Mark, Popovic Relja, Waring Jeffrey, Riley-Gillis Bridget, Lehtonen Anne, Schutzman Jennifer, Hunkapiller Julie, Bowers Natalie, Pendergrass Rion, Kulkarni Diptee, Auro Kirsi, Porello Alessandro, Loboda Andrey, Lehtonen Heli, McDonough Stefan, Vuoti Sauli, Kaarniranta Kai, Turunen Joni A, Ollila Terhi, Uusitalo Hannu, Karjalainen Juha, Pitkänen Esa, Liu Mengzhen, Runz Heiko, Loomis Stephanie, Strauss Erich, Bowers Natalie, Chen Hao, Pendergrass Rion, Tasanen Kaisa, Huilaja Laura, Hannula-Jouppi Katariina, Salmi Teea, Peltonen Sirkku, Koulu Leena, Smaoui Nizar, Rahimov Fedik, Lehtonen Anne, Choy David, Pendergrass Rion, Waterworth Dawn, Kalpala Kirsi, Wu Ying, Pussinen Pirkko, Salminen Aino, Salo Tuula, Rice David, Nieminen Pekka, Palotie Ulla, Siponen Maria, Suominen Liisa, Mäntylä Päivi, Gursoy Ulvi, Anttonen Vuokko, Sipilä Kirsi, Pendergrass Rion, Laivuori Hannele, Kurra Venla, Kotaniemi-Talonen Laura, Heikinheimo Oskari, Kalliala Ilkka, Aaltonen Lauri, Jokimaa Varpu, Kettunen Johannes, Vääräsmäki Marja, Uimari Outi, Morin-Papunen Laure, Niinimäki Maarit, Piltonen Terhi, Kivinen Katja, Widen Elisabeth, Tukiainen Taru, Reeve Mary Pat, Daly Mark, Välimäki Niko, Laakkonen Eija, Tyrmi Jaakko, Silven Heidi, Sliz Eeva, Arffman Riikka, Savukoski Susanna, Laisk Triin, Pujol Natalia, Liu Mengzhen, Riley-Gillis Bridget, Pendergrass Rion, Kumar Janet, Auro Kirsi, Hovatta Iiris, Chen Chia-Yen, Isometsä Erkki, Ollila Hanna, Suvisaari Jaana, Als Thomas Damm, Mäkitie Antti, Bizaki-Vallaskangas Argyro, Toppila-Salmi Sanna, Willberg Tytti, Saarentaus Elmo, Aarnisalo Antti, Salminen Eveliina, Rahikkala Elisa, Kettunen Johannes, Aittomäki Kristiina, Åberg Fredrik, Kurki Mitja, Ripatti Samuli, Daly Mark, Karjalainen Juha, Havulinna Aki, Mehtonen Juha, Palta Priit, Hassan Shabbeer, Parolo Pietro Della Briotta, Zhou Wei, Maasha Mutaamba, Hassan Shabbeer, Lemmelä Susanna, Rivas Manuel, Niemi Mari E, Palotie Aarno, Liu Aoxing, Lehisto Arto, Ganna Andrea, Llorens Vincent, Laivuori Hannele, Tukiainen Taru, Reeve Mary Pat, Heyne Henrike, Mars Nina, Rämö Joel, Saarentaus Elmo, Ollila Hanna, Rodosthenous Rodos, Strausz Satu, Palotie Tuula, Palin Kimmo, Garcia-Tabuenca Javier, Siirtola Harri, Kiiskinen Tuomo, Lee Jiwoo, Tsuo Kristin, Elliott Amanda, Kristiansson Kati, Arvas Mikko, Hyvärinen Kati, Ritari Jarmo, Carpén Olli, Kettunen Johannes, Pylkäs Katri, Sliz Eeva, Karjalainen Minna, Mantere Tuomo, Kangasniemi Eeva, Heikkinen Sami, Mannermaa Arto, Laakkonen Eija, Pitkänen Nina, Lessard Samuel, Chatelain Clément, Terho Perttu, Soini Sirpa, Partanen Jukka, Punkka Eero, Serpi Raisa, Siltanen Sanna, Kosma Veli-Matti, Kuopio Teijo, Jalanko Anu, Shen Huei-Yi, Kajanne Risto, Aavikko Mervi, Palin Henna, Linna Malla-Maria, Kurki Mitja, Karjalainen Juha, Parolo Pietro Della Briotta, Lehisto Arto, Mehtonen Juha, Zhou Wei, Kanai Masahiro, Maasha Mutaamba, Laivuori Hannele, Havulinna Aki, Lemmelä Susanna, Kiiskinen Tuomo, Lahtela L Elisa, Kaunisto Mari, Kilpeläinen Elina, Sipilä Timo P, Dada Oluwaseun Alexander, Ghazal Awaisa, Kytölä Anastasia, Weldatsadik Rigbe, Ruotsalainen Sanni, Donner Kati, Sipilä Timo P, Loukola Anu, Laiho Päivi, Sistonen Tuuli, Kaiharju Essi, Laukkanen Markku, Järvensivu Elina, Lähteenmäki Sini, Männikkö Lotta, Wong Regis, Toivola Auli, Brunfeldt Minna, Mattsson Hannele, Kristiansson Kati, Lemmelä Susanna, Koskelainen Sami, Hiekkalinna Tero, Paajanen Teemu, Palta Priit, Pärn Kalle, Kals Mart, Luo Shuang, Laitinen Tarja, Reeve Mary Pat, Padmanabhuni Shanmukha Sampath, Niemi Marianna, Siirtola Harri, Gracia-Tabuenca Javier, Helminen Mika, Luukkaala Tiina, Vähätalo Iida, Pitkänen Jyrki, Hautalahti Marco, Mäkelä Johanna, Smith Sarah, Southerington Tom, Kauko Anni3, Niiranen Teemu345,
Affiliation:
1. Division of Perioperative Services, Intensive Care and Pain Medicine, Turku University Hospital , Turku, Finland 2. Department of Anesthesiology and Intensive Care, University of Turku , Turku, Finland 3. Department of Internal Medicine, University of Turku , Turku, Finland 4. Division of Medicine, Turku University Hospital , Turku, Finland 5. Department of Public Health Solutions, Finnish Institute for Health and Welfare , Turku, Finland
Abstract
Abstract
Men and women have differing risks of adverse events after revascularization procedures and these differences could be partially driven by genetics. We studied the sex-specific differences in associations of polygenic risk scores (PRSs) with atrial fibrillation (AF), ischaemic stroke (STR), intracranial haemorrhage (ICH), myocardial infarction (MI) and gastrointestinal haemorrhage (GIH) in coronary revascularization patients. The study cohort comprised 5561 and 17 578 revascularized women and men. All participants underwent genotyping and register-based follow-up from 1961 to 2021. We calculated PRSs for all individuals and used Cox models with interaction term to examine the sex-specific associations between the PRSs and adverse outcomes after revascularization. The AF-PRS was more strongly associated with AF in men [hazard ratio (HR) per 1 standard deviation increase, 1.16; 95% confidence interval (CI), 1.12–1.19; P = 7.6 × 10−22) than in women (P for interaction 0.006). Conversely, ICH-PRS was more strongly associated with ICH after revascularization in women (HR, 1.32; 95% CI, 1.08–1.62; P = 0.008) than in men (P for interaction 0.008). We observed no sex-specific differences for the associations of PRSs with STR, MI or GIH. The genetic risk of AF after revascularization is greater in men than in women, and vice versa for ICH. Sex-specific PRSs could be used to identify individuals in high genetic risk for these complications.
Funder
Business Finland AbbVie AstraZeneca Biogen Bristol Myers Squibb Genentech Merck Sharp & Dohme Pfizer GlaxoSmithKline Sanofi Maze Therapeutics Janssen Biotech Novartis and Boehringer Ingelheim
Publisher
Oxford University Press (OUP)
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