Sebastian E Baumeister1, André Karch2, Martin Bahls2, Alexander Teumer2, Michael F Leitzmann2, Hansjörg Baurecht2. 1. From Epidemiology (S.E.B.), LMU München, UNIKA-T Augsburg; Independent Research Group, Clinical Epidemiology (S.E.B.), Helmholtz Zentrum München, German Research Center for Environmental Health, Munich; Institute of Epidemiology and Social Medicine (A.K.), University of Münster; Department of Internal Medicine B (M.B.) and Institute for Community Medicine (A.T.), University Medicine Greifswald; DZHK (German Centre for Cardiovascular Research) (M.B., A.T.), Partner Site Greifswald; and Department of Epidemiology and Preventive Medicine (M.F.L., H.B.), University of Regensburg, Germany. s.baumeister@unika-t.de. 2. From Epidemiology (S.E.B.), LMU München, UNIKA-T Augsburg; Independent Research Group, Clinical Epidemiology (S.E.B.), Helmholtz Zentrum München, German Research Center for Environmental Health, Munich; Institute of Epidemiology and Social Medicine (A.K.), University of Münster; Department of Internal Medicine B (M.B.) and Institute for Community Medicine (A.T.), University Medicine Greifswald; DZHK (German Centre for Cardiovascular Research) (M.B., A.T.), Partner Site Greifswald; and Department of Epidemiology and Preventive Medicine (M.F.L., H.B.), University of Regensburg, Germany.
Abstract
OBJECTIVE: Evidence from observational studies for the effect of physical activity on the risk of Alzheimer disease (AD) is inconclusive. We performed a 2-sample mendelian randomization analysis to examine whether physical activity is protective for AD. METHODS: Summary data of genome-wide association studies on physical activity and AD were used. The primary study population included 21,982 patients with AD and 41,944 cognitively normal controls. Eight single nucleotide polymorphisms (SNPs) known at p < 5 × 10-8 to be associated with average accelerations and 8 SNPs associated at p < 5 × 10-7 with vigorous physical activity (fraction of accelerations >425 milligravities) served as instrumental variables. RESULTS: There was no association between genetically predicted average accelerations with the risk of AD (inverse variance weighted odds ratio [OR] per SD increment: 1.03, 95% confidence interval 0.97-1.10, p = 0.332). Genetic liability for fraction of accelerations >425 milligravities was unrelated to AD risk. CONCLUSION: The present study does not support a causal association between physical activity and risk of AD.
OBJECTIVE: Evidence from observational studies for the effect of physical activity on the risk of Alzheimer disease (AD) is inconclusive. We performed a 2-sample mendelian randomization analysis to examine whether physical activity is protective for AD. METHODS: Summary data of genome-wide association studies on physical activity and AD were used. The primary study population included 21,982 patients with AD and 41,944 cognitively normal controls. Eight single nucleotide polymorphisms (SNPs) known at p < 5 × 10-8 to be associated with average accelerations and 8 SNPs associated at p < 5 × 10-7 with vigorous physical activity (fraction of accelerations >425 milligravities) served as instrumental variables. RESULTS: There was no association between genetically predicted average accelerations with the risk of AD (inverse variance weighted odds ratio [OR] per SD increment: 1.03, 95% confidence interval 0.97-1.10, p = 0.332). Genetic liability for fraction of accelerations >425 milligravities was unrelated to AD risk. CONCLUSION: The present study does not support a causal association between physical activity and risk of AD.
Authors: Jacqueline M Vink; Dorret I Boomsma; Sarah E Medland; Marleen H M de Moor; Janine H Stubbe; Belinda K Cornes; Nicholas G Martin; Axel Skytthea; Kirsten O Kyvik; Richard J Rose; Urho M Kujala; Jaakko Kaprio; Jennifer R Harris; Nancy L Pedersen; Lynn Cherkas; Tim D Spector; Eco J C de Geus Journal: Twin Res Hum Genet Date: 2011-02 Impact factor: 1.587
Authors: Brian W Kunkle; Benjamin Grenier-Boley; Rebecca Sims; Joshua C Bis; Vincent Damotte; Adam C Naj; Anne Boland; Maria Vronskaya; Sven J van der Lee; Alexandre Amlie-Wolf; Céline Bellenguez; Aura Frizatti; Vincent Chouraki; Eden R Martin; Kristel Sleegers; Nandini Badarinarayan; Johanna Jakobsdottir; Kara L Hamilton-Nelson; Sonia Moreno-Grau; Robert Olaso; Rachel Raybould; Yuning Chen; Amanda B Kuzma; Mikko Hiltunen; Taniesha Morgan; Shahzad Ahmad; Badri N Vardarajan; Jacques Epelbaum; Per Hoffmann; Merce Boada; Gary W Beecham; Jean-Guillaume Garnier; Denise Harold; Annette L Fitzpatrick; Otto Valladares; Marie-Laure Moutet; Amy Gerrish; Albert V Smith; Liming Qu; Delphine Bacq; Nicola Denning; Xueqiu Jian; Yi Zhao; Maria Del Zompo; Nick C Fox; Seung-Hoan Choi; Ignacio Mateo; Joseph T Hughes; Hieab H Adams; John Malamon; Florentino Sanchez-Garcia; Yogen Patel; Jennifer A Brody; Beth A Dombroski; Maria Candida Deniz Naranjo; Makrina Daniilidou; Gudny Eiriksdottir; Shubhabrata Mukherjee; David Wallon; James Uphill; Thor Aspelund; Laura B Cantwell; Fabienne Garzia; Daniela Galimberti; Edith Hofer; Mariusz Butkiewicz; Bertrand Fin; Elio Scarpini; Chloe Sarnowski; Will S Bush; Stéphane Meslage; Johannes Kornhuber; Charles C White; Yuenjoo Song; Robert C Barber; Sebastiaan Engelborghs; Sabrina Sordon; Dina Voijnovic; Perrie M Adams; Rik Vandenberghe; Manuel Mayhaus; L Adrienne Cupples; Marilyn S Albert; Peter P De Deyn; Wei Gu; Jayanadra J Himali; Duane Beekly; Alessio Squassina; Annette M Hartmann; Adelina Orellana; Deborah Blacker; Eloy Rodriguez-Rodriguez; Simon Lovestone; Melissa E Garcia; Rachelle S Doody; Carmen Munoz-Fernadez; Rebecca Sussams; Honghuang Lin; Thomas J Fairchild; Yolanda A Benito; Clive Holmes; Hata Karamujić-Čomić; Matthew P Frosch; Hakan Thonberg; Wolfgang Maier; Gennady Roshchupkin; Bernardino Ghetti; Vilmantas Giedraitis; Amit Kawalia; Shuo Li; Ryan M Huebinger; Lena Kilander; Susanne Moebus; Isabel Hernández; M Ilyas Kamboh; RoseMarie Brundin; James Turton; Qiong Yang; Mindy J Katz; Letizia Concari; Jenny Lord; Alexa S Beiser; C Dirk Keene; Seppo Helisalmi; Iwona Kloszewska; Walter A Kukull; Anne Maria Koivisto; Aoibhinn Lynch; Lluís Tarraga; Eric B Larson; Annakaisa Haapasalo; Brian Lawlor; Thomas H Mosley; Richard B Lipton; Vincenzo Solfrizzi; Michael Gill; W T Longstreth; Thomas J Montine; Vincenza Frisardi; Monica Diez-Fairen; Fernando Rivadeneira; Ronald C Petersen; Vincent Deramecourt; Ignacio Alvarez; Francesca Salani; Antonio Ciaramella; Eric Boerwinkle; Eric M Reiman; Nathalie Fievet; Jerome I Rotter; Joan S Reisch; Olivier Hanon; Chiara Cupidi; A G Andre Uitterlinden; Donald R Royall; Carole Dufouil; Raffaele Giovanni Maletta; Itziar de Rojas; Mary Sano; Alexis Brice; Roberta Cecchetti; Peter St George-Hyslop; Karen Ritchie; Magda Tsolaki; Debby W Tsuang; Bruno Dubois; David Craig; Chuang-Kuo Wu; Hilkka Soininen; Despoina Avramidou; Roger L Albin; Laura Fratiglioni; Antonia Germanou; Liana G Apostolova; Lina Keller; Maria Koutroumani; Steven E Arnold; Francesco Panza; Olymbia Gkatzima; Sanjay Asthana; Didier Hannequin; Patrice Whitehead; Craig S Atwood; Paolo Caffarra; Harald Hampel; Inés Quintela; Ángel Carracedo; Lars Lannfelt; David C Rubinsztein; Lisa L Barnes; Florence Pasquier; Lutz Frölich; Sandra Barral; Bernadette McGuinness; Thomas G Beach; Janet A Johnston; James T Becker; Peter Passmore; Eileen H Bigio; Jonathan M Schott; Thomas D Bird; Jason D Warren; Bradley F Boeve; Michelle K Lupton; James D Bowen; Petra Proitsi; Adam Boxer; John F Powell; James R Burke; John S K Kauwe; Jeffrey M Burns; Michelangelo Mancuso; Joseph D Buxbaum; Ubaldo Bonuccelli; Nigel J Cairns; Andrew McQuillin; Chuanhai Cao; Gill Livingston; Chris S Carlson; Nicholas J Bass; Cynthia M Carlsson; John Hardy; Regina M Carney; Jose Bras; Minerva M Carrasquillo; Rita Guerreiro; Mariet Allen; Helena C Chui; Elizabeth Fisher; Carlo Masullo; Elizabeth A Crocco; Charles DeCarli; Gina Bisceglio; Malcolm Dick; Li Ma; Ranjan Duara; Neill R Graff-Radford; Denis A Evans; Angela Hodges; Kelley M Faber; Martin Scherer; Kenneth B Fallon; Matthias Riemenschneider; David W Fardo; Reinhard Heun; Martin R Farlow; Heike Kölsch; Steven Ferris; Markus Leber; Tatiana M Foroud; Isabella Heuser; Douglas R Galasko; Ina Giegling; Marla Gearing; Michael Hüll; Daniel H Geschwind; John R Gilbert; John Morris; Robert C Green; Kevin Mayo; John H Growdon; Thomas Feulner; Ronald L Hamilton; Lindy E Harrell; Dmitriy Drichel; Lawrence S Honig; Thomas D Cushion; Matthew J Huentelman; Paul Hollingworth; Christine M Hulette; Bradley T Hyman; Rachel Marshall; Gail P Jarvik; Alun Meggy; Erin Abner; Georgina E Menzies; Lee-Way Jin; Ganna Leonenko; Luis M Real; Gyungah R Jun; Clinton T Baldwin; Detelina Grozeva; Anna Karydas; Giancarlo Russo; Jeffrey A Kaye; Ronald Kim; Frank Jessen; Neil W Kowall; Bruno Vellas; Joel H Kramer; Emma Vardy; Frank M LaFerla; Karl-Heinz Jöckel; James J Lah; Martin Dichgans; James B Leverenz; David Mann; Allan I Levey; Stuart Pickering-Brown; Andrew P Lieberman; Norman Klopp; Kathryn L Lunetta; H-Erich Wichmann; Constantine G Lyketsos; Kevin Morgan; Daniel C Marson; Kristelle Brown; Frank Martiniuk; Christopher Medway; Deborah C Mash; Markus M Nöthen; Eliezer Masliah; Nigel M Hooper; Wayne C McCormick; Antonio Daniele; Susan M McCurry; Anthony Bayer; Andrew N McDavid; John Gallacher; Ann C McKee; Hendrik van den Bussche; Marsel Mesulam; Carol Brayne; Bruce L Miller; Steffi Riedel-Heller; Carol A Miller; Joshua W Miller; Ammar Al-Chalabi; John C Morris; Christopher E Shaw; Amanda J Myers; Jens Wiltfang; Sid O'Bryant; John M Olichney; Victoria Alvarez; Joseph E Parisi; Andrew B Singleton; Henry L Paulson; John Collinge; William R Perry; Simon Mead; Elaine Peskind; David H Cribbs; Martin Rossor; Aimee Pierce; Natalie S Ryan; Wayne W Poon; Benedetta Nacmias; Huntington Potter; Sandro Sorbi; Joseph F Quinn; Eleonora Sacchinelli; Ashok Raj; Gianfranco Spalletta; Murray Raskind; Carlo Caltagirone; Paola Bossù; Maria Donata Orfei; Barry Reisberg; Robert Clarke; Christiane Reitz; A David Smith; John M Ringman; Donald Warden; Erik D Roberson; Gordon Wilcock; Ekaterina Rogaeva; Amalia Cecilia Bruni; Howard J Rosen; Maura Gallo; Roger N Rosenberg; Yoav Ben-Shlomo; Mark A Sager; Patrizia Mecocci; Andrew J Saykin; Pau Pastor; Michael L Cuccaro; Jeffery M Vance; Julie A Schneider; Lori S Schneider; Susan Slifer; William W Seeley; Amanda G Smith; Joshua A Sonnen; Salvatore Spina; Robert A Stern; Russell H Swerdlow; Mitchell Tang; Rudolph E Tanzi; John Q Trojanowski; Juan C Troncoso; Vivianna M Van Deerlin; Linda J Van Eldik; Harry V Vinters; Jean Paul Vonsattel; Sandra Weintraub; Kathleen A Welsh-Bohmer; Kirk C Wilhelmsen; Jennifer Williamson; Thomas S Wingo; Randall L Woltjer; Clinton B Wright; Chang-En Yu; Lei Yu; Yasaman Saba; Alberto Pilotto; Maria J Bullido; Oliver Peters; Paul K Crane; David Bennett; Paola Bosco; Eliecer Coto; Virginia Boccardi; Phil L De Jager; Alberto Lleo; Nick Warner; Oscar L Lopez; Martin Ingelsson; Panagiotis Deloukas; Carlos Cruchaga; Caroline Graff; Rhian Gwilliam; Myriam Fornage; Alison M Goate; Pascual Sanchez-Juan; Patrick G Kehoe; Najaf Amin; Nilifur Ertekin-Taner; Claudine Berr; Stéphanie Debette; Seth Love; Lenore J Launer; Steven G Younkin; Jean-Francois Dartigues; Chris Corcoran; M Arfan Ikram; Dennis W Dickson; Gael Nicolas; Dominique Campion; JoAnn Tschanz; Helena Schmidt; Hakon Hakonarson; Jordi Clarimon; Ron Munger; Reinhold Schmidt; Lindsay A Farrer; Christine Van Broeckhoven; Michael C O'Donovan; Anita L DeStefano; Lesley Jones; Jonathan L Haines; Jean-Francois Deleuze; Michael J Owen; Vilmundur Gudnason; Richard Mayeux; Valentina Escott-Price; Bruce M Psaty; Alfredo Ramirez; Li-San Wang; Agustin Ruiz; Cornelia M van Duijn; Peter A Holmans; Sudha Seshadri; Julie Williams; Phillippe Amouyel; Gerard D Schellenberg; Jean-Charles Lambert; Margaret A Pericak-Vance Journal: Nat Genet Date: 2019-02-28 Impact factor: 41.307
Authors: Joris Deelen; Daniel S Evans; Dan E Arking; Niccolò Tesi; Marianne Nygaard; Xiaomin Liu; Mary K Wojczynski; Mary L Biggs; Ashley van der Spek; Gil Atzmon; Erin B Ware; Chloé Sarnowski; Albert V Smith; Ilkka Seppälä; Heather J Cordell; Janina Dose; Najaf Amin; Alice M Arnold; Kristin L Ayers; Nir Barzilai; Elizabeth J Becker; Marian Beekman; Hélène Blanché; Kaare Christensen; Lene Christiansen; Joanna C Collerton; Sarah Cubaynes; Steven R Cummings; Karen Davies; Birgit Debrabant; Jean-François Deleuze; Rachel Duncan; Jessica D Faul; Claudio Franceschi; Pilar Galan; Vilmundur Gudnason; Tamara B Harris; Martijn Huisman; Mikko A Hurme; Carol Jagger; Iris Jansen; Marja Jylhä; Mika Kähönen; David Karasik; Sharon L R Kardia; Andrew Kingston; Thomas B L Kirkwood; Lenore J Launer; Terho Lehtimäki; Wolfgang Lieb; Leo-Pekka Lyytikäinen; Carmen Martin-Ruiz; Junxia Min; Almut Nebel; Anne B Newman; Chao Nie; Ellen A Nohr; Eric S Orwoll; Thomas T Perls; Michael A Province; Bruce M Psaty; Olli T Raitakari; Marcel J T Reinders; Jean-Marie Robine; Jerome I Rotter; Paola Sebastiani; Jennifer Smith; Thorkild I A Sørensen; Kent D Taylor; André G Uitterlinden; Wiesje van der Flier; Sven J van der Lee; Cornelia M van Duijn; Diana van Heemst; James W Vaupel; David Weir; Kenny Ye; Yi Zeng; Wanlin Zheng; Henne Holstege; Douglas P Kiel; Kathryn L Lunetta; P Eline Slagboom; Joanne M Murabito Journal: Nat Commun Date: 2019-08-14 Impact factor: 14.919
Authors: Stephen Burgess; George Davey Smith; Neil M Davies; Frank Dudbridge; Dipender Gill; M Maria Glymour; Fernando P Hartwig; Michael V Holmes; Cosetta Minelli; Caroline L Relton; Evropi Theodoratou Journal: Wellcome Open Res Date: 2020-04-28
Authors: Sara A Galle; Jun Liu; Bruno Bonnechère; Najaf Amin; Maarten M Milders; Jan Berend Deijen; Erik J A Scherder; Madeleine L Drent; Trudy Voortman; M Arfan Ikram; Cornelia M van Duijn Journal: Eur J Epidemiol Date: 2022-09-27 Impact factor: 12.434
Authors: Jill P Pell; Frederick K Ho; Carlos Celis-Morales; Fanny Petermann-Rocha; Donald M Lyall; Stuart R Gray; Jason M R Gill; Naveed Sattar; Paul Welsh; Terence J Quinn; William Stewart Journal: BMC Med Date: 2021-12-02 Impact factor: 8.775