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1. TWINGEN: protocol for an observational clinical biobank recall and biomarker cohort study to identify Finnish individuals with high risk of Alzheimer’s disease

Author

Tommi Vasankari, Henri Vähä-Ypyä, Oskari Heikinheimo, Athena Matakidou, Jaakko Kaprio, Eero Vuoksimaa, Ying Wu, Kai Kaarniranta, Peeter Karihtala, Wei Zhou, Caroline Fox, Sanna-Kaisa Herukka, Sarah Smith, Apinya Lertratanakul, Katri Kaukinen, Johannes Kettunen, Minna Männikkö, Eeva Sliz, Markus Perola, Veikko Salomaa, Hilkka Soininen, Ilkka Kalliala, Mika Kähönen, Hao Chen, Andrey Loboda, Laure Morin-Papunen, Terhi Piltonen, Anders Mälarstig, Jason Miller, Jussi Hernesniemi, Henrike Heyne, Sirkku Peltonen, Daniel Gordin, Masahiro Kanai, Benjamin Challis, Juha Sinisalo, David Rice, Fredrik Åberg, Aarno Palotie, Samuli Ripatti, Oili Kaipiainen-Seppänen, Aki Havulinna, Satu Strausz, Tuomo Kiiskinen, Sanni Ruotsalainen, Jukka Koskela, Tuula Palotie, Mark Daly, Howard Jacob, Heiko Runz, Sally John, Robert Plenge, Mark McCarthy, Julie Hunkapiller, Dawn Waterworth, Petri Virolainen, Terhi Kilpi, Jukka Partanen, Anne Pitkäranta, Veli-Matti Kosma, Outi Tuovila, Raimo Pakkanen, Shameek Biswas, Xinli Hu, Johanna Schleutker, Mikko Arvas, Olli Carpen, Reetta Hinttala, Arto Mannermaa, Valtteri Julkunen, Anne Remes, Reetta Kälviäinen, Mikko Hiltunen, Jukka Peltola, Pentti Tienari, Juha Rinne, Adam Ziemann, Jeffrey Waring, Nizar Smaoui, Anne Lehtonen, Susan Eaton, Sanni Lahdenperä, Natalie Bowers, Edmond Teng, Fanli Xu, David Pulford, Martti Färkkilä, Sampsa Pikkarainen, Airi Jussila, Timo Blomster, Mikko Kiviniemi, Markku Voutilainen, Fedik Rahimov, Joseph Maranville, Tim Lu, Kirsi Kalpala, Melissa Miller, Linda McCarthy, Kari Eklund, Antti Palomäki, Pia Isomäki, Laura Pirilä, Johanna Huhtakangas, Marla Hochfeld, Nan Bing, Jorge Esparza Gordillo, Nina Mars, Tarja Laitinen, Margit Pelkonen, Paula Kauppi, Hannu Kankaanranta, Terttu Harju, Hubert Chen, Teemu Niiranen, Kaj Metsärinne, Marja-Riitta Taskinen, Tiinamaija Tuomi, Jari Laukkanen, Audrey Chu, Jaakko Parkkinen, Heikki Joensuu, Tuomo Meretoja, Lauri Aaltonen, Annika Auranen, Päivi Auvinen, Klaus Elenius, Relja Popovic, Bridget Riley-Gillis, Jennifer Schutzman, Heli Lehtonen, Stefan McDonough, Diptee Kulkarni, Terhi Ollila, Hannu Uusitalo, Erich Strauss, Kaisa Tasanen, Laura Huilaja, Katariina Hannula-Jouppi, Teea Salmi, Leena Koulu, David Choy, Anu Jalanko, Risto Kajanne, Mari Kaunisto, Chia-Yen Chen, Robert Yang, Kirsi Auro, Clement Chatelain, Mitja Kurki, Juha Karjalainen, Kimmo Palin, Priit Palta, Susanna Lemmelä, Manuel Rivas, Arto Lehisto, Andrea Ganna, Vincent Llorens, Kati Kristiansson, Kati Hyvärinen, Jarmo Ritari, Katri Pylkäs, Minna Karjalainen, Tuomo Mantere, Eeva Kangasniemi, Sami Heikkinen, Eija Laakkonen, Anu Loukola, Päivi Laiho, Tuuli Sistonen, Essi Kaiharju, Markku Laukkanen, Elina Järvensivu, Sini Lähteenmäki, Lotta Männikkö, Regis Wong, Hannele Mattsson, Tero Hiekkalinna, Kati Donner, Kalle Pärn, Elina Kilpeläinen, Hannele Laivuori, Harri Siirtola, Sirpa Soini, Teijo Kuopio, Ioanna Tachmazidou, Katja Kivinen, Pekka Nieminen, Adam Platt, Sanna Toppila-Salmi, Antti Mäkitie, Elmo Saarentaus, Kristiina Aittomäki, Elisabeth Widen, Marja Vääräsmäki, Erkki Isometsä, Laura Addis, Mika Helminen, Taneli Raivio, Mart Kals, Majd Mouded, Hanna Ollila, Vuokko Anttonen, Tarja Kokkola, Robert Graham, Amanda Elliott, Ali Abbasi, Bridget Riley-Gills, Dirk Paul, Katherine Klinger, Deepak Raipal, Antti Hakanen, Raisa Serpi, Johanna Mäkelä, Mengzhen Liu, Neha Raghavan, Adriana Huertas-Vazquez, Nicole Renaud, Roosa Kallionpää, John Eicher, Minna Raivio, Juulia Partanen, Riitta Lahesmaa, Glenda Lassi, Joanna Betts, Rajashree Mishra, Felix Vaura, Joel Rämö, Mary Pat Reeve, Johanna Mattson, Sauli Vuoti, Esa Pitkänen, Joni A Turunen, Stephanie Loomis, Pirkko Pussinen, Aino Salminen, Tuula Salo, Ulla Palotie, Maria Siponen, Liisa Suominen, Päivi Mäntylä, Ulvi Gursoy, Kirsi Sipilä, Venla Kurra, Laura Kotaniemi-Talonen, Outi Uimari, Taru Tukiainen, Niko Välimäki, Janet Kumar, Juha Mehtonen, Shabbeer Hassan, Pietro Della Briotta Parolo, Mutaamba Maasha, Javier Garcia-Tabuenca, Jiwoo Lee, Kristin Tsuo, Nina Pitkänen, Eero Punkka, Huei-Yi Shen, Mervi Aavikko, L. Elisa Lahtela, Timo P. Sipilä, Awaisa Ghazal, Sami Koskelainen, Teemu Paajanen, Shuang Luo, Javier Gracia-Tabuenca, Tiina Luukkaala, Iida Vähätalo, Marco Hautalahti, Tom Southerington, Paula Iso-Markku, Jaana Suvisaari, Zhihao Ding, Qingqin S Li, Amy Hart, Perttu Terho, Alessandro Porello, Anastasia Kytölä, Antti Aarnisalo, Aoxing Liu, Argyro Bizaki-Vallaskangas, Auli Toivola, Debby Ngo, Dermot Reilly, Ekaterina Khramtsova, Elisa Rahikkala, Eric Green, Eveliina Salminen, Fabiana Farias, George Okafo, Heidi Silven, Heli Salminen-Mankonen, Henna Palin, Iiris Hovatta, Jaakko Tyrmi, Jae-Hoon Sul, Jenni Aittokallio, Jyrki Pitkänen, Karen He, Katriina Aalto-Setälä, Maarit Niinimäki, Malla-Maria Linna, Marc Jung, Margaret G. Ehm, Marianna Niemi, Meijian Guan, Mike Mendelson, Minna Brunfeldt, Natalia Pujol, Nathan Lawless, Oluwaseun Alexander Dada, Rigbe Weldatsadik, Riikka Arffman, Rion Pendergrass, Sahar Mozaffari, Samuel Lessard, Sanna Siltanen, Shanmukha Sampath Padmanabhuni, Simonne Longerich, Susanna Savukoski, Thomas Damm Als, Timo Hiltunen, Tomi P. Mäkelä, Triin Laisk, Tytti Willberg, Varpu Jokimaa, Aija Kyttälä, Toni T Saari, Aino Aaltonen, Sari Aaltonen, Sari Kärkkäinen, Hilkka Liedes, Miina Ollikainen, Teemu Palviainen, Ilona Ruotsalainen, Mia Urjansson, Markus M Forsberg, Jaakko Lähteenmäki, Pia Nyberg, Jani Tikkanen, Mari E. Niemi, and Rodos Rodosthenous

Subjects
Medicine
Abstract

Introduction A better understanding of the earliest stages of Alzheimer’s disease (AD) could expedite the development or administration of treatments. Large population biobanks hold the promise to identify individuals at an elevated risk of AD and related dementias based on health registry information. Here, we establish the protocol for an observational clinical recall and biomarker study called TWINGEN with the aim to identify individuals at high risk of AD by assessing cognition, health and AD-related biomarkers. Suitable candidates were identified and invited to participate in the new study among THL Biobank donors according to TWINGEN study criteria.Methods and analysis A multi-centre study (n=800) to obtain blood-based biomarkers, telephone-administered and web-based memory and cognitive parameters, questionnaire information on lifestyle, health and psychological factors, and accelerometer data for measures of physical activity, sedentary behaviour and sleep. A subcohort is being asked to participate in an in-person neuropsychological assessment (n=200) and wear an Oura ring (n=50). All participants in the TWINGEN study have genome-wide genotyping data and up to 48 years of follow-up data from the population-based older Finnish Twin Cohort (FTC) study of the University of Helsinki. The data collected in TWINGEN will be returned to THL Biobank from where it can later be requested for other biobank studies such as FinnGen that supported TWINGEN.Ethics and dissemination This recall study consists of FTC/THL Biobank/FinnGen participants whose data were acquired in accordance with the Finnish Biobank Act. The recruitment protocols followed the biobank protocols approved by Finnish Medicines Agency. The TWINGEN study plan was approved by the Ethics Committee of Hospital District of Helsinki and Uusimaa (number 16831/2022). THL Biobank approved the research plan with the permission no: THLBB2022_83.

Published
2024
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2. Recontacting biobank participants to collect lifestyle, behavioural and cognitive information via online questionnaires: lessons from a pilot study within FinnGen

Author

Oskari Heikinheimo, Athena Matakidou, Jaakko Kaprio, Ying Wu, Kai Kaarniranta, Peeter Karihtala, Wei Zhou, Caroline Fox, Sarah Smith, Apinya Lertratanakul, Katri Kaukinen, Johannes Kettunen, Eeva Sliz, Markus Perola, Veikko Salomaa, Hilkka Soininen, Ilkka Kalliala, Mika Kähönen, Hao Chen, Andrey Loboda, Laure Morin-Papunen, Terhi Piltonen, Anders Mälarstig, Jason Miller, Jussi Hernesniemi, Henrike Heyne, Sirkku Peltonen, Daniel Gordin, Masahiro Kanai, Benjamin Challis, Juha Sinisalo, David Rice, Fredrik Åberg, Aarno Palotie, Samuli Ripatti, Oili Kaipiainen-Seppänen, Aki Havulinna, Satu Strausz, Tuomo Kiiskinen, Sanni Ruotsalainen, Jukka Koskela, Tuula Palotie, Mark Daly, Howard Jacob, Heiko Runz, Sally John, Robert Plenge, Mark McCarthy, Julie Hunkapiller, Dawn Waterworth, Petri Virolainen, Terhi Kilpi, Jukka Partanen, Anne Pitkäranta, Veli-Matti Kosma, Outi Tuovila, Raimo Pakkanen, Shameek Biswas, Xinli Hu, Johanna Schleutker, Mikko Arvas, Olli Carpen, Reetta Hinttala, Arto Mannermaa, Valtteri Julkunen, Anne Remes, Reetta Kälviäinen, Mikko Hiltunen, Jukka Peltola, Pentti Tienari, Juha Rinne, Adam Ziemann, Jeffrey Waring, Nizar Smaoui, Anne Lehtonen, Susan Eaton, Sanni Lahdenperä, Natalie Bowers, Edmond Teng, Fanli Xu, David Pulford, Martti Färkkilä, Sampsa Pikkarainen, Airi Jussila, Timo Blomster, Mikko Kiviniemi, Markku Voutilainen, Fedik Rahimov, Joseph Maranville, Tim Lu, Kirsi Kalpala, Melissa Miller, Linda McCarthy, Kari Eklund, Antti Palomäki, Pia Isomäki, Laura Pirilä, Johanna Huhtakangas, Marla Hochfeld, Nan Bing, Jorge Esparza Gordillo, Nina Mars, Tarja Laitinen, Margit Pelkonen, Paula Kauppi, Hannu Kankaanranta, Terttu Harju, Hubert Chen, Teemu Niiranen, Kaj Metsärinne, Marja-Riitta Taskinen, Tiinamaija Tuomi, Jari Laukkanen, Audrey Chu, Jaakko Parkkinen, Heikki Joensuu, Tuomo Meretoja, Lauri Aaltonen, Annika Auranen, Päivi Auvinen, Klaus Elenius, Relja Popovic, Jennifer Schutzman, Heli Lehtonen, Stefan McDonough, Diptee Kulkarni, Terhi Ollila, Hannu Uusitalo, Erich Strauss, Kaisa Tasanen, Laura Huilaja, Katariina Hannula-Jouppi, Teea Salmi, Leena Koulu, David Choy, Anu Jalanko, Risto Kajanne, Mari Kaunisto, Chia-Yen Chen, Robert Yang, Kirsi Auro, Clement Chatelain, Mitja Kurki, Juha Karjalainen, Kimmo Palin, Priit Palta, Susanna Lemmelä, Manuel Rivas, Arto Lehisto, Andrea Ganna, Vincent Llorens, Kati Kristiansson, Kati Hyvärinen, Jarmo Ritari, Katri Pylkäs, Minna Karjalainen, Tuomo Mantere, Eeva Kangasniemi, Sami Heikkinen, Eija Laakkonen, Anu Loukola, Päivi Laiho, Tuuli Sistonen, Essi Kaiharju, Markku Laukkanen, Elina Järvensivu, Sini Lähteenmäki, Lotta Männikkö, Regis Wong, Hannele Mattsson, Kati Donner, Kalle Pärn, Elina Kilpeläinen, Hannele Laivuori, Harri Siirtola, Lila Kallio, Sirpa Soini, Teijo Kuopio, Ioanna Tachmazidou, Katja Kivinen, Pekka Nieminen, Adam Platt, Sanna Toppila-Salmi, Antti Mäkitie, Elmo Saarentaus, Kristiina Aittomäki, Elisabeth Widen, Marja Vääräsmäki, Erkki Isometsä, Jari Lahti, Laura Addis, Taneli Raivio, Mart Kals, Majd Mouded, Hanna Ollila, Vuokko Anttonen, Robert Graham, Amanda Elliott, Ali Abbasi, Bridget Riley-Gills, Dirk Paul, Katherine Klinger, Deepak Raipal, Antti Hakanen, Raisa Serpi, Johanna Mäkelä, Mengzhen Liu, Neha Raghavan, Adriana Huertas-Vazquez, Nicole Renaud, Roosa Kallionpää, John Eicher, Minna Raivio, Juulia Partanen, Riitta Lahesmaa, Glenda Lassi, Joanna Betts, Rajashree Mishra, Felix Vaura, Joel Rämö, Mary Pat Reeve, Johanna Mattson, Sauli Vuoti, Esa Pitkänen, Joni A Turunen, Stephanie Loomis, Pirkko Pussinen, Aino Salminen, Tuula Salo, Ulla Palotie, Maria Siponen, Liisa Suominen, Päivi Mäntylä, Ulvi Gursoy, Kirsi Sipilä, Venla Kurra, Laura Kotaniemi-Talonen, Outi Uimari, Taru Tukiainen, Niko Välimäki, Janet Kumar, Juha Mehtonen, Shabbeer Hassan, Pietro Della Briotta Parolo, Mutaamba Maasha, Javier Garcia-Tabuenca, Jiwoo Lee, Kristin Tsuo, Nina Pitkänen, Eero Punkka, Huei-Yi Shen, Mervi Aavikko, L. Elisa Lahtela, Timo P. Sipilä, Awaisa Ghazal, Sami Koskelainen, Teemu Paajanen, Shuang Luo, Tiina Luukkaala, Iida Vähätalo, Tero Jyrhämä, Marco Hautalahti, Tom Southerington, Jaana Suvisaari, Zhihao Ding, Qingqin S Li, Amy Hart, Rodosthenis S Rodosthenous, Mari E K Niemi, Merja Perala, Perttu Terho, Theresa Knopp, Enni M Makkonen, Paula Nurmi, Pauli Wihuri, Corianna Moffatt, Paolo Martini, Laura Germine, Viola A Makela, Oona A Karhunen, Tero S Hiekkalinna, Alessandro Porello, Anastasia Kytölä, Antti Aarnisalo, Aoxing Liu, Argyro Bizaki-Vallaskangas, Auli Toivola, Debby Ngo, Dermot Reilly, Ekaterina Khramtsova, Elisa Rahikkala, Eric Green, Eveliina Salminen, Fabiana Farias, George Okafo, Heidi Silven, Heli Salminen-Mankonen, Henna Palin, Iiris Hovatta, Jaakko Tyrmi, Jae-Hoon Sul, Jenni Aittokallio, Jyrki Pitkänen, Karen He, Katriina Aalto-Setälä, Maarit Niinimäki, Malla-Maria Linna, Marc Jung, Margaret G. Ehm, Marianna Niemi, Meijian Guan, Mike Mendelson, Minna Brunfeldt, Natalia Pujol, Nathan Lawless, Oluwaseun Alexander Dada, Rigbe Weldatsadik, Riikka Arffman, Rion Pendergrass, Sahar Mozaffari, Samuel Lessard, Sanna Siltanen, Shanmukha Sampath Padmanabhuni, Simonne Longerich, Susanna Savukoski, Thomas Damm Als, Timo Hiltunen, Tomi P. Mäkelä, Triin Laisk, Tytti Willberg, and Varpu Jokimaa

Subjects
Medicine
Abstract

Objectives To recontact biobank participants and collect cognitive, behavioural and lifestyle information via a secure online platform.Design Biobank-based recontacting pilot study.Setting Three Finnish biobanks (Helsinki, Auria, Tampere) recruiting participants from February 2021 to July 2021.Participants All eligible invitees were enrolled in FinnGen by their biobanks (Helsinki, Auria, Tampere), had available genetic data and were >18 years old. Individuals with severe neuropsychiatric disease or cognitive or physical disabilities were excluded. Lastly, 5995 participants were selected based on their polygenic score for cognitive abilities and invited to the study. Among invitees, 1115 had successfully participated and completed the study questionnaire(s).Outcome measures The primary outcome was the participation rate among study invitees. Secondary outcomes included questionnaire completion rate, quality of data collected and comparison of participation rate boosting strategies.Results The overall participation rate was 18.6% among all invitees and 23.1% among individuals aged 18–69. A second reminder letter yielded an additional 9.7% participation rate in those who did not respond to the first invitation. Recontacting participants via an online healthcare portal yielded lower participation than recontacting via physical letter. The completion rate of the questionnaire and cognitive tests was high (92% and 85%, respectively), and measurements were overall reliable among participants. For example, the correlation (r) between self-reported body mass index and that collected by the biobanks was 0.92.Conclusion In summary, this pilot suggests that recontacting FinnGen participants with the goal to collect a wide range of cognitive, behavioural and lifestyle information without additional engagement results in a low participation rate, but with reliable data. We suggest that such information be collected at enrolment, if possible, rather than via post hoc recontacting.

Published
2022
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3. Risk of Midlife Stroke After Adverse Pregnancy Outcomes: The FinnGen Study

Author

Eliza C. Miller, Anni Kauko, Sarah E. Tom, Hannele Laivuori, Teemu Niiranen, Natalie A. Bello, Aarno Palotie, Mark Daly, Bridget Riley-Gills, Howard Jacob, Dirk Paul, Athena Matakidou, Adam Platt, Heiko Runz, Sally John, George Okafo, Nathan Lawless, Heli Salminen-Mankonen, Robert Plenge, Joseph Maranville, Mark McCarthy, Julie Hunkapiller, Margaret G. Ehm, Kirsi Auro, Simonne Longerich, Caroline 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, Taneli Raivio, Raisa Serpi, Tarja Laitinen, Veli-Matti Kosma, Jari Laukkanen, Marco Hautalahti, Outi Tuovila, Raimo Pakkanen, Jeffrey Waring, Bridget Riley-Gillis, Fedik Rahimov, Ioanna Tachmazidou, Chia-Yen Chen, Zhihao Ding, Marc Jung, Shameek Biswas, 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, Arto Mannermaa, Katriina Aalto-Setälä, Mika Kähönen, Johanna Mäkelä, Reetta Kälviäinen, Valtteri Julkunen, Hilkka Soininen, Anne Remes, Mikko Hiltunen, Jukka Peltola, Minna Raivio, Pentti Tienari, Juha Rinne, Roosa Kallionpää, Juulia Partanen, Ali Abbasi, Adam Ziemann, Nizar Smaoui, Anne Lehtonen, Susan Eaton, Sanni Lahdenperä, Natalie Bowers, Edmond Teng, Fanli Xu, Laura Addis, John Eicher, Qingqin S Li, Karen He, Ekaterina Khramtsova, Martti Färkkilä, Jukka Koskela, Sampsa Pikkarainen, Airi Jussila, Katri Kaukinen, Timo Blomster, Mikko Kiviniemi, Markku Voutilainen, Tim Lu, Linda McCarthy, Amy Hart, Meijian Guan, Jason Miller, Kirsi Kalpala, Melissa Miller, Kari Eklund, Antti Palomäki, Pia Isomäki, Laura Pirilä, Oili Kaipiainen-Seppänen, Johanna Huhtakangas, Nina Mars, Apinya Lertratanakul, Marla Hochfeld, Jorge Esparza Gordillo, Fabiana Farias, Nan Bing, Margit Pelkonen, Paula Kauppi, Hannu Kankaanranta, Terttu Harju, Riitta Lahesmaa, Glenda Lassi, Hubert Chen, Joanna Betts, Rajashree Mishra, Majd Mouded, Debby Ngo, Felix Vaura, Veikko Salomaa, Kaj Metsärinne, Jenni Aittokallio, Jussi Hernesniemi, Daniel Gordin, Juha Sinisalo, Marja-Riitta Taskinen, Tiinamaija Tuomi, Timo Hiltunen, Amanda Elliott, Mary Pat Reeve, Sanni Ruotsalainen, Benjamin Challis, Audrey Chu, Dermot Reilly, Mike Mendelson, Jaakko Parkkinen, Tuomo Meretoja, Heikki Joensuu, Johanna Mattson, Eveliina Salminen, Annika Auranen, Peeter Karihtala, Päivi Auvinen Klaus Elenius, Esa Pitkänen, Relja Popovic, Jennifer Schutzman, Diptee Kulkarni, Alessandro Porello, Andrey Loboda, Heli Lehtonen, Stefan McDonough, Sauli Vuoti, Kai Kaarniranta, Joni A Turunen, Terhi Ollila, Hannu Uusitalo, Juha Karjalainen, Mengzhen Liu, Stephanie Loomis, Erich Strauss, Hao Chen, Kaisa Tasanen, Laura Huilaja, Katariina Hannula-Jouppi, Teea Salmi, Sirkku Peltonen, Leena Koulu, David Choy, Ying Wu, Pirkko Pussinen, Aino Salminen, Tuula Salo, David Rice, Pekka Nieminen, Ulla Palotie, Maria Siponen, Liisa Suominen, Päivi Mäntylä, Ulvi Gursoy, Vuokko Anttonen, Kirsi Sipilä, Venla Kurra, Laura Kotaniemi-Talonen, Oskari Heikinheimo, Ilkka Kalliala, Lauri Aaltonen, Varpu Jokimaa, Marja Vääräsmäki, Outi Uimari, Laure Morin-Papunen, Maarit Niinimäki, Terhi Piltonen, Katja Kivinen, Elisabeth Widen, Taru Tukiainen, Niko Välimäki, Eija Laakkonen, Jaakko Tyrmi, Heidi Silven, Eeva Sliz, Riikka Arffman, Susanna Savukoski, Triin Laisk, Natalia Pujol, Janet Kumar, Iiris Hovatta, Erkki Isometsä, Hanna Ollila, Jaana Suvisaari, Thomas Damm Als, Antti Mäkitie, Argyro Bizaki-Vallaskangas, Sanna Toppila-Salmi, Tytti Willberg, Elmo Saarentaus, Antti Aarnisalo, Elisa Rahikkala, Kristiina Aittomäki, Fredrik Åberg, Mitja Kurki, Aki Havulinna, Juha Mehtonen, Priit Palta, Shabbeer Hassan, Pietro Della, Briotta Parolo, Wei Zhou, Mutaamba Maasha, Susanna Lemmelä, Manuel Rivas, Mari E. Niemi, Aoxing Liu, Arto Lehisto, Andrea Ganna, Vincent Llorens, Henrike Heyne, Joel Rämö, Rodos Rodosthenous, Satu Strausz, Tuula Palotie, Kimmo Palin, Javier Garcia-Tabuenca, Harri Siirtola, Tuomo Kiiskinen, Jiwoo Lee, Kristin Tsuo, Kati Kristiansson, Kati Hyvärinen, Jarmo Ritari, Katri Pylkäs, Minna Karjalainen, Tuomo Mantere, Eeva Kangasniemi, Sami Heikkinen, Nina Pitkänen, Samuel Lessard, Clément Chatelain, Perttu Terho, Sirpa Soini, Eero Punkka, Sanna Siltanen, Teijo Kuopio, Anu Jalanko, Huei-Yi Shen, Risto Kajanne, Mervi Aavikko, Henna Palin, Malla-Maria Linna, Masahiro Kanai, L. Elisa Lahtela, Mari Kaunisto, Elina Kilpeläinen, Timo P. Sipilä, Oluwaseun Alexander Dada, Awaisa Ghazal, Anastasia Kytölä, Rigbe Weldatsadik, Kati Donner, Anu Loukola, Päivi Laiho, Tuuli Sistonen, Essi Kaiharju, Markku Laukkanen, Elina Järvensivu, Sini Lähteenmäki, Lotta Männikkö, Regis Wong, Auli Toivola, Minna Brunfeldt, Hannele Mattsson, Sami Koskelainen, Tero Hiekkalinna, Teemu Paajanen, Kalle Pärn, Mart Kals, Shuang Luo, Shanmukha Sampath Padmanabhuni, Marianna Niemi, Javier Gracia-Tabuenca, Mika Helminen, Tiina Luukkaala, Iida Vähätalo, Jyrki Pitkänen, Sarah Smith, and Tom Southerington

Subjects
Advanced and Specialized Nursing, Neurology (clinical), Cardiology and Cardiovascular Medicine
Abstract

BACKGROUND: Adverse pregnancy outcomes (APO) contribute to higher risk of maternal cerebrovascular disease, but longitudinal data that include APO and stroke timing are lacking. We hypothesized that APO are associated with younger age at first stroke, with a stronger relationship in those with >1 pregnancy with APO. METHODS: We analyzed longitudinal Finnish nationwide health registry data from the FinnGen Study. We included women who gave birth after 1969 when the hospital discharge registry was established. We defined APO as a pregnancy affected by gestational hypertension, preeclampsia, eclampsia, preterm birth, small for gestational age infant, or placental abruption. We defined stroke as first hospital admission for ischemic stroke or nontraumatic intracerebral or subarachnoid hemorrhage, excluding stroke during pregnancy or within 1 year postpartum. We used Kaplan-Meier survival curves and multivariable-adjusted Cox and generalized linear models to assess the relationship between APO and future stroke. RESULTS: We included 144 306 women with a total of 316 789 births in the analysis sample, of whom 17.9% had at least 1 pregnancy with an APO and 2.9% experienced an APO in ≥2 pregnancies. Women with APO had more comorbidities including obesity, hypertension, heart disease, and migraine. Median age at first stroke was 58.3 years in those with no APO, 54.8 years in those with 1 APO, and 51.6 years in those with recurrent APO. In models adjusted for sociodemographic characteristics and stroke risk factors, risk of stroke was greater in women with 1 APO (adjusted hazard ratio, 1.3 [95% CI, 1.2–1.4]) and recurrent APO (adjusted hazard ratio, 1.4 [95% CI, 1.2–1.7]) compared with those with no APO. Women with recurrent APO had more than twice the stroke risk before age 45 (adjusted odds ratio, 2.1 [95% CI, 1.5–3.1]) compared with those without APO. CONCLUSIONS: Women who experience APO have earlier onset of cerebrovascular disease, with the earliest onset in those with more than 1 affected pregnancy.

Published
2023

4. Genome-wide association and multi-omics studies identify MGMT as a novel risk gene for Alzheimer's disease among women

Author

Jaeyoon Chung, Anjali Das, Xinyu Sun, Débora R. Sobreira, Yuk Yee Leung, Catherine Igartua, Sahar Mozaffari, Yi‐Fan Chou, Sam Thiagalingam, Jesse Mez, Xiaoling Zhang, Gyungah R. Jun, Thor D. Stein, Brian W. Kunkle, Eden R. Martin, Margaret A. Pericak‐Vance, Richard Mayeux, Jonathan L. Haines, Gerard D. Schellenberg, Marcelo A. Nobrega, Kathryn L. Lunetta, Jayant M. Pinto, Li‐San Wang, Carole Ober, and Lindsay A. Farrer

Subjects
Psychiatry and Mental health, Cellular and Molecular Neuroscience, Developmental Neuroscience, Epidemiology, Health Policy, Neurology (clinical), Geriatrics and Gerontology
Abstract

Variants in the tau gene (MAPT) region are associated with breast cancer in women and Alzheimer's disease (AD) among persons lacking apolipoprotein E ε4 (ε4-).To identify novel genes associated with tau-related pathology, we conducted two genome-wide association studies (GWAS) for AD, one among 10,340 ε4- women in the Alzheimer's Disease Genetics Consortium (ADGC) and another in 31 members (22 women) of a consanguineous Hutterite kindred.We identified novel associations of AD with MGMT variants in the ADGC (rs12775171, odds ratio [OR] = 1.4, P = 4.9 × 10These findings suggest that epigenetically regulated MGMT expression is involved in AD pathogenesis, especially in women.

Published
2022

6. Video Games: A Site for Sore Eyes

Author

Sahar Mozaffari

Subjects
education.field_of_study, Visual acuity, media_common.quotation_subject, Visual impairment, Population, Forestry, Plant Science, Action (philosophy), Blurred vision, Perception, Accidental, medicine, Optometry, medicine.symptom, education, Psychology, Agronomy and Crop Science, Video game, Neuroscience, media_common
Abstract

V ideo G ames : A S ite for S ore E yes Sahar Mozaffari B S J This paper will address three distinct areas of research in which video games are being used to im- prove eye and brain conditions in the medical field. “I was very surprised by this finding,” research Roger Li, PhD, of the School of Optometry and the Helen Wills Neuroscience Institute at University of California, Berke- ley said in a news release. “I didn’t expect to see this type of improvement.” From the earliest days in the history of video games, accusations (whether true or not) have circulated suggesting that they somehow negatively im- Figure 1. A Play Station 2 contoller, used to control the movements of characters in video games. pact society, specifically the juvenile and adolescent life- style. However, recent studies suggest that video games may prove to be useful treatment methods in the field of vision science. It has been assumed that video games are detrimental to vision, in the same way that staring at any electronic screen for long periods of time has been traditionally discouraged. However, the accidental discovery of using video games to cure adult amblyopia, more commonly known as “lazy eye,” has provided a basis to help those without perfect vision in a non-clinical way as opposed to contact lenses, glasses, or laser surgery. This study is one of the first to show that playing games can improve blurred vision in adults with amblyopia (Li, On September 21, 2010, an issue of PLoS Biology pub- lished a study in which people with amblyopia showed improvement in their vision after playing video games. Amblyopia is improvable in children through treatment, but is more difficult to treat in adults. After playing 40 hours of video games, adults with amblyopia showed an 1 • B erkeley S cientific J ournal • A ccidents • V olume 14 • I ssue 2 improvement in visual acuity and 3-D depth perception (Li, 2010). According to the National Eye Institute, amblyo- pia is a brain disorder in which the vision of one eye does not develop properly (Li, 2010). It is the most frequent type of permanent visual impairment in children, affecting two to three of every 100 children (Li, 2010). Amblyopia is also the most common cause of one-eye visual impairment among young adults or people of middle age (Li, 2010). While the study has shown vision improve- ment for adults with amblyopia, researchers say this does not necessarily justify spending more time playing video games for the general population, as there have been no observations of similar benefits for people with normal vision (Li, 2010). “These new findings are very encouraging because there are currently no accepted treatments for adults with amblyopia,” says Dennis Levi, of University of Cali- fornia, Berkeley and Dean of Optometry at the Helen Wills Neuroscience Institute. Levi says that conventional wisdom has held that unless the disorder is corrected in childhood, damage was thought to be irreversible. Li and Levi said they have found that intensive training on a perceptual task, such as getting two horizontal lines to align, can lead to an improvement of 30 percent to 40 “Video games may prove to be useful treatment methods in the field of vision science.” percent in visual acuity (Li, 2010). In one experiment, 10 subjects with patches over the stronger eye played an action video game for two hours at a time for a total of 40 hours in one month. The action video game required subjects to shoot at targets, while the non-action game consisted of users having to construct things on screen. Twenty subjects participated in this study between the ages of 20 and 60. In another experiment, three people played the

Published
2011

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