Genetic Risk Factors Associated With Preeclampsia and Hypertensive Disorders of Pregnancy-Reference-Cited by-同舟云学术

Genetic Risk Factors Associated With Preeclampsia and Hypertensive Disorders of Pregnancy

Published:2023-07-01 Issue:7 Volume:8 Page:674
ISSN:2380-6583
Container-title:JAMA Cardiology
language:en
Short-container-title:JAMA Cardiol

Author:

Tyrmi Jaakko S.¹²³,Kaartokallio Tea⁴,Lokki A. Inkeri⁴⁵,Jääskeläinen Tiina⁴⁶,Kortelainen Eija⁴,Ruotsalainen Sanni⁷,Karjalainen Juha⁷⁸⁹,Ripatti Samuli⁷⁹¹⁰,Kivioja Anna¹,Laisk Triin¹¹,Kettunen Johannes³¹²,Pouta Anneli¹²,Kivinen Katja⁷,Kajantie Eero¹³¹⁴¹⁵¹⁶,Heinonen Seppo¹⁷,Kere Juha¹⁸¹⁹,Laivuori Hannele¹⁴⁷²⁰,Ekholm Eeva²¹,Hietala Reija²¹,Keski-Nisula Leea²¹,Mäkikallio Kaarin²¹,Uotila Jukka²¹,Sainio Susanna²¹,Saisto Terhi²¹,Vääräsmäki Marja²¹,Aalto-Viljakainen Tia²¹,Georgiadis Leena²¹,Heikkinen-Eloranta Jenni²¹,Klemetti Miira M.²¹,Suomalainen-König Sanna²¹,Wedenoja Satu²¹,Leminen Satu²¹,Lähdesmäki Aija²¹,Mehtälä Susanna²¹,Salmén Christina²¹,Palotie Aarno²¹,Daly Mark²¹,Riley-Gills Bridget²¹,Jacob Howard²¹,Paul Dirk²¹,Matakidou Athena²¹,Platt Adam²¹,Runz Heiko²¹,John Sally²¹,Okafo George²¹,Lawless Nathan²¹,Plenge Robert²¹,Maranville Joseph²¹,McCarthy Mark²¹,Hunkapiller Julie²¹,Ehm Margaret G.²¹,Auro Kirsi²¹,Longerich Simonne²¹,Fox Caroline²¹,Mälarstig Anders²¹,Klinger Katherine²¹,Raipal Deepak²¹,Green Eric²¹,Graham Robert²¹,Yang Robert²¹,O´Donnell Chris²¹,Mäkelä Tomi P.²¹,Kaprio Jaakko²¹,Virolainen Petri²¹,Hakanen Antti²¹,Kilpi Terhi²¹,Perola Markus²¹,Partanen Jukka²¹,Pitkäranta Anne²¹,Junttila Juhani²¹,Serpi Raisa²¹,Laitinen Tarja²¹,Kosma Veli-Matti²¹,Laukkanen Jari²¹,Hautalahti Marco²¹,Tuovila Outi²¹,Pakkanen Raimo²¹,Waring Jeffrey²¹,Riley-Gillis Bridget²¹,Rahimov Fedik²¹,Tachmazidou Ioanna²¹,Chen Chia-Yen²¹,Ding Zhihao²¹,Jung Marc²¹,Biswas Shameek²¹,Pendergrass Rion²¹,Pulford David²¹,Raghavan Neha²¹,Huertas-Vazquez Adriana²¹,Sul Jae-Hoon²¹,Hu Xinli²¹,Mozaffari Sahar²¹,Waterworth Dawn²¹,Renaud Nicole²¹,Obeidat Ma´en²¹,Schleutker Johanna²¹,Arvas Mikko²¹,Carpén Olli²¹,Hinttala Reetta²¹,Mannermaa Arto²¹,Aalto-Setälä Katriina²¹,Kähönen Mika²¹,Mäkelä Johanna²¹,Kälviäinen Reetta²¹,Julkunen Valtteri²¹,Soininen Hilkka²¹,Remes Anne²¹,Hiltunen Mikko²¹,Peltola Jukka²¹,Raivio Minna²¹,Tienari Pentti²¹,Rinne Juha²¹,Kallionpää Roosa²¹,Partanen Juulia²¹,Abbasi Ali²¹,Ziemann Adam²¹,Smaoui Nizar²¹,Lehtonen Anne²¹,Eaton Susan²¹,Lahdenperä Sanni²¹,Bowers Natalie²¹,Teng Edmond²¹,Xu Fanli²¹,Addis Laura²¹,Eicher John²¹,Li Qingqin S²¹,He Karen²¹,Khramtsova Ekaterina²¹,Färkkilä Martti²¹,Koskela Jukka²¹,Pikkarainen Sampsa²¹,Jussila Airi²¹,Kaukinen Katri²¹,Blomster Timo²¹,Kiviniemi Mikko²¹,Voutilainen Markku²¹,Lu Tim²¹,McCarthy Linda²¹,Hart Amy²¹,Guan Meijian²¹,Miller Jason²¹,Kalpala Kirsi²¹,Miller Melissa²¹,Eklund Kari²¹,Palomäki Antti²¹,Isomäki Pia²¹,Pirilä Laura²¹,Kaipiainen-Seppänen Oili²¹,Huhtakangas Johanna²¹,Mars Nina²¹,Lertratanakul Apinya²¹,Close David²¹,Hochfeld Marla²¹,Gordillo Jorge Esparza²¹,Farias Fabiana²¹,Bing Nan²¹,Pelkonen Margit²¹,Kauppi Paula²¹,Kankaanranta Hannu²¹,Harju Terttu²¹,Lahesmaa Riitta²¹,Mackay Alex²¹,Lassi Glenda²¹,Chen Hubert²¹,Betts Joanna²¹,Mishra Rajashree²¹,Mouded Majd²¹,Ngo Debby²¹,Niiranen Teemu²¹,Vaura Felix²¹,Salomaa Veikko²¹,Metsärinne Kaj²¹,Aittokallio Jenni²¹,Hernesniemi Jussi²¹,Gordin Daniel²¹,Sinisalo Juha²¹,Taskinen Marja-Riitta²¹,Tuomi Tiinamaija²¹,Hiltunen Timo²¹,Elliott Amanda²¹,Reeve Mary Pat²¹,Challis Benjamin²¹,Chu Audrey²¹,Reilly Dermot²¹,Mendelson Mike²¹,Parkkinen Jaakko²¹,Meretoja Tuomo²¹,Joensuu Heikki²¹,Mattson Johanna²¹,Salminen Eveliina²¹,Auranen Annika²¹,Karihtala Peeter²¹,Auvinen Päivi²¹,Elenius Klaus²¹,Pitkänen Esa²¹,Popovic Relja²¹,Schutzman Jennifer²¹,Kulkarni Diptee²¹,Porello Alessandro²¹,Loboda Andrey²¹,Lehtonen Heli²¹,McDonough Stefan²¹,Vuoti Sauli²¹,Kaarniranta Kai²¹,Turunen Joni A²¹,Ollila Terhi²¹,Uusitalo Hannu²¹,Liu Mengzhen²¹,Loomis Stephanie²¹,Strauss Erich²¹,Chen Hao²¹,Tasanen Kaisa²¹,Huilaja Laura²¹,Hannula-Jouppi Katariina²¹,Salmi Teea²¹,Peltonen Sirkku²¹,Koulu Leena²¹,Choy David²¹,Wu Ying²¹,Pussinen Pirkko²¹,Salminen Aino²¹,Salo Tuula²¹,Rice David²¹,Nieminen Pekka²¹,Palotie Ulla²¹,Siponen Maria²¹,Suominen Liisa²¹,Mäntylä Päivi²¹,Gursoy Ulvi²¹,Anttonen Vuokko²¹,Sipilä Kirsi²¹,Kurra Venla²¹,Kotaniemi-Talonen Laura²¹,Heikinheimo Oskari²¹,Kalliala Ilkka²¹,Aaltonen Lauri²¹,Jokimaa Varpu²¹,Kettunen Johannes²¹,Uimari Outi²¹,Morin-Papunen Laure²¹,Niinimäki Maarit²¹,Piltonen Terhi²¹,Widen Elisabeth²¹,Tukiainen Taru²¹,Välimäki Niko²¹,Laakkonen Eija²¹,Silven Heidi²¹,Sliz Eeva²¹,Arffman Riikka²¹,Savukoski Susanna²¹,Pujol Natalia²¹,Kumar Janet²¹,Hovatta Iiris²¹,Isometsä Erkki²¹,Veerapen Kumar²¹,Ollila Hanna²¹,Suvisaari Jaana²¹,Als Thomas D.²¹,Mäkitie Antti²¹,Bizaki-Vallaskangas Argyro²¹,Toppila-Salmi Sanna²¹,Willberg Tytti²¹,Saarentaus Elmo²¹,Aarnisalo Antti²¹,Rahikkala Elisa²¹,Aittomäki Kristiina²¹,Åberg Fredrik²¹,Kurki Mitja²¹,Ripatti Samuli²¹,Karjalainen Juha²¹,Havulinna Aki²¹,Mehtonen Juha²¹,Palta Priit²¹,Hassan Shabbeer²¹,Parolo Pietro Della Briotta²¹,Zhou Wei²¹,Maasha Mutaamba²¹,Lemmelä Susanna²¹,Rivas Manuel²¹,Niemi Mari E.²¹,Liu Aoxing²¹,Lehisto Arto²¹,Ganna Andrea²¹,Llorens Vincent²¹,Heyne Henrike²¹,Rämö Joel²¹,Rodosthenous Rodos²¹,Strausz Satu²¹,Palotie Tuula²¹,Palin Kimmo²¹,Garcia-Tabuenca Javier²¹,Siirtola Harri²¹,Kiiskinen Tuomo²¹,Lee Jiwoo²¹,Tsuo Kristin²¹,Kristiansson Kati²¹,Hyvärinen Kati²¹,Ritari Jarmo²¹,Pylkäs Katri²¹,Karjalainen Minna²¹,Mantere Tuomo²¹,Kangasniemi Eeva²¹,Heikkinen Sami²¹,Pitkänen Nina²¹,Lessard Samuel²¹,Chatelain Clément²¹,Terho Perttu²¹,Soini Sirpa²¹,Punkka Eero²¹,Siltanen Sanna²¹,Kuopio Teijo²¹,Jalanko Anu²¹,Shen Huei-Yi²¹,Kajanne Risto²¹,Aavikko Mervi²¹,Kanai Masahiro²¹,Laivuori Hannele²¹,Lahtela L. Elisa²¹,Kaunisto Mari²¹,Kilpeläinen Elina²¹,Sipilä Timo P.²¹,Dada Oluwaseun Alexander²¹,Ghazal Awaisa²¹,Kytölä Anastasia²¹,Weldatsadik Rigbe²¹,Donner Kati²¹,Loukola Anu²¹,Laiho Päivi²¹,Sistonen Tuuli²¹,Kaiharju Essi²¹,Laukkanen Markku²¹,Järvensivu Elina²¹,Lähteenmäki Sini²¹,Männikkö Lotta²¹,Wong Regis²¹,Toivola Auli²¹,Brunfeldt Minna²¹,Mattsson Hannele²¹,Koskelainen Sami²¹,Hiekkalinna Tero²¹,Paajanen Teemu²¹,Pärn Kalle²¹,Kals Mart²¹,Luo Shuang²¹,Sinha Vishal²¹,Niemi Marianna²¹,Gracia-Tabuenca Javier²¹,Helminen Mika²¹,Luukkaala Tiina²¹,Vähätalo Iida²¹,Pitkänen Jyrki²¹,Smith Sarah²¹,Southerington Tom²¹,Metspalu Andres²¹,Esko Tõnu²¹,Nelis Mari²¹,Milani Lili²¹,Mägi Reedik²¹,Hudjashov Georgi²¹,

Affiliation:

1. Center for Child, Adolescent and Maternal Health Research, Faculty of Medicine and Health Technology, Tampere University, Tampere, Finland

2. Center for Life Course Health Research, Faculty of Medicine, University of Oulu, Oulu, Finland

3. Biocenter Oulu, University of Oulu, Oulu, Finland

4. Department of Medical and Clinical Genetics, University of Helsinki and Helsinki University Hospital, Helsinki, Finland

5. Department of Bacteriology and Immunology, University of Helsinki and Helsinki University Hospital, Helsinki, Finland

6. Department of Food and Nutrition, University of Helsinki, Helsinki, Finland

7. Institute for Molecular Medicine Finland, Helsinki Institute of Life Science, University of Helsinki, Helsinki, Finland

8. Analytic and Translational Genetics Unit, Massachusetts General Hospital and Harvard Medical School, Boston

9. Broad Institute of the Massachusetts Institute of Technology and Harvard University, Cambridge

10. Department of Public Health, University of Helsinki, Helsinki, Finland

11. Estonian Genome Centre, Institute of Genomics, University of Tartu, Tartu, Estonia

12. Finnish Institute for Health and Welfare, Helsinki, Finland

13. PEDEGO Research Unit (Research Unit for Pediatrics, Dermatology, Clinical Genetics, Obstetrics and Gynecology), Medical Research Center Oulu, Oulu University Hospital and University of Oulu, Oulu, Finland

14. Population Health Unit, Finnish Institute for Health and Welfare, Helsinki and Oulu, Finland

15. Children’s Hospital, University of Helsinki and Helsinki University Hospital, Helsinki, Finland

16. Department of Clinical and Molecular Medicine, Norwegian University of Health and Technology, Trondheim, Norway

17. Department of Obsterics and Gynaecology, University of Helsinki and Helsinki University Hospital, Helsinki, Finland

18. Department of Biosciences and Nutrition, Karolinska Institutet, Huddinge, Sweden

19. Folkhälsan Research Center and Stem Cells and Metabolism Research Program, University of Helsinki, Helsinki, Finland

20. Department of Obstetrics and Gynecology, Tampere University Hospital, Tampere, Finland

21. for the FINNPEC Study Group, FinnGen Project, and the Estonian Biobank Research Team

Abstract

ImportanceA genetic contribution to preeclampsia susceptibility has been established but is still incompletely understood.ObjectiveTo disentangle the underlying genetic architecture of preeclampsia and preeclampsia or other maternal hypertension during pregnancy with a genome-wide association study (GWAS) of hypertensive disorders of pregnancy.Design, Setting, and ParticipantsThis GWAS included meta-analyses in maternal preeclampsia and a combination phenotype encompassing maternal preeclampsia and preeclampsia or other maternal hypertensive disorders. Two overlapping phenotype groups were selected for examination, namely, preeclampsia and preeclampsia or other maternal hypertension during pregnancy. Data from the Finnish Genetics of Pre-eclampsia Consortium (FINNPEC, 1990-2011), Finnish FinnGen project (1964-2019), Estonian Biobank (1997-2019), and the previously published InterPregGen consortium GWAS were combined. Individuals with preeclampsia or other maternal hypertension during pregnancy and control individuals were selected from the cohorts based on relevant International Classification of Diseases codes. Data were analyzed from July 2020 to February 2023.ExposuresThe association of a genome-wide set of genetic variants and clinical risk factors was analyzed for the 2 phenotypes.ResultsA total of 16 743 women with prior preeclampsia and 15 200 with preeclampsia or other maternal hypertension during pregnancy were obtained from FINNPEC, FinnGen, Estonian Biobank, and the InterPregGen consortium study (respective mean [SD] ages at diagnosis: 30.3 [5.5], 28.7 [5.6], 29.7 [7.0], and 28 [not available] years). The analysis found 19 genome-wide significant associations, 13 of which were novel. Seven of the novel loci harbor genes previously associated with blood pressure traits (NPPA, NPR3, PLCE1, TNS2, FURIN, RGL3, and PREX1). In line with this, the 2 study phenotypes showed genetic correlation with blood pressure traits. In addition, novel risk loci were identified in the proximity of genes involved in the development of placenta (PGR, TRPC6, ACTN4, and PZP), remodeling of uterine spiral arteries (NPPA, NPPB, NPR3, and ACTN4), kidney function (PLCE1, TNS2, ACTN4, and TRPC6), and maintenance of proteostasis in pregnancy serum (PZP).Conclusions and RelevanceThe findings indicate that genes related to blood pressure traits are associated with preeclampsia, but many of these genes have additional pleiotropic effects on cardiometabolic, endothelial, and placental function. Furthermore, several of the associated loci have no known connection with cardiovascular disease but instead harbor genes contributing to maintenance of successful pregnancy, with dysfunctions leading to preeclampsialike symptoms.

Publisher

American Medical Association (AMA)

Subject

Cardiology and Cardiovascular Medicine

Link

https://jamanetwork.com/journals/jamacardiology/articlepdf/2805948/jamacardiology_tyrmi_2023_oi_230025_1688580076.42703.pdf

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