Xiaofeng Zhu1. 1. Department of Population and Quantitative Health Sciences, School of Medicine, Case Western Reserve University, Cleveland, OH 44106, USA.
Abstract
BACKGROUND: Mendelian randomization (MR) analysis has become popular in inferring and estimating the causality of an exposure on an outcome due to the success of genome wide association studies. Many statistical approaches have been developed and each of these methods require specific assumptions. RESULTS: In this article, we review the pros and cons of these methods. We use an example of high-density lipoprotein cholesterol on coronary artery disease to illuminate the challenges in Mendelian randomization investigation. CONCLUSION: The current available MR approaches allow us to study causality among risk factors and outcomes. However, novel approaches are desirable for overcoming multiple source confounding of risk factors and an outcome in MR analysis.
BACKGROUND: Mendelian randomization (MR) analysis has become popular in inferring and estimating the causality of an exposure on an outcome due to the success of genome wide association studies. Many statistical approaches have been developed and each of these methods require specific assumptions. RESULTS: In this article, we review the pros and cons of these methods. We use an example of high-density lipoprotein cholesterol on coronary artery disease to illuminate the challenges in Mendelian randomization investigation. CONCLUSION: The current available MR approaches allow us to study causality among risk factors and outcomes. However, novel approaches are desirable for overcoming multiple source confounding of risk factors and an outcome in MR analysis.
Authors: Xiaofeng Zhu; Tao Feng; Bamidele O Tayo; Jingjing Liang; J Hunter Young; Nora Franceschini; Jennifer A Smith; Lisa R Yanek; Yan V Sun; Todd L Edwards; Wei Chen; Mike Nalls; Ervin Fox; Michele Sale; Erwin Bottinger; Charles Rotimi; Yongmei Liu; Barbara McKnight; Kiang Liu; Donna K Arnett; Aravinda Chakravati; Richard S Cooper; Susan Redline Journal: Am J Hum Genet Date: 2014-12-11 Impact factor: 11.025
Authors: A Schatzkin; E Lanza; D Corle; P Lance; F Iber; B Caan; M Shike; J Weissfeld; R Burt; M R Cooper; J W Kikendall; J Cahill Journal: N Engl J Med Date: 2000-04-20 Impact factor: 91.245
Authors: Amy R Bentley; Yun J Sung; Michael R Brown; Thomas W Winkler; Aldi T Kraja; Ioanna Ntalla; Kenneth Rice; Patricia B Munroe; Alanna C Morrison; Dabeeru C Rao; Charles N Rotimi; L Adrienne Cupples; Karen Schwander; Daniel I Chasman; Elise Lim; Xuan Deng; Xiuqing Guo; Jingmin Liu; Yingchang Lu; Ching-Yu Cheng; Xueling Sim; Dina Vojinovic; Jennifer E Huffman; Solomon K Musani; Changwei Li; Mary F Feitosa; Melissa A Richard; Raymond Noordam; Jenna Baker; Guanjie Chen; Hugues Aschard; Traci M Bartz; Jingzhong Ding; Rajkumar Dorajoo; Alisa K Manning; Tuomo Rankinen; Albert V Smith; Salman M Tajuddin; Wei Zhao; Mariaelisa Graff; Maris Alver; Mathilde Boissel; Jin Fang Chai; Xu Chen; Jasmin Divers; Evangelos Evangelou; Chuan Gao; Anuj Goel; Yanick Hagemeijer; Sarah E Harris; Fernando P Hartwig; Meian He; Andrea R V R Horimoto; Fang-Chi Hsu; Yi-Jen Hung; Anne U Jackson; Anuradhani Kasturiratne; Pirjo Komulainen; Brigitte Kühnel; Karin Leander; Keng-Hung Lin; Jian'an Luan; Leo-Pekka Lyytikäinen; Nana Matoba; Ilja M Nolte; Maik Pietzner; Bram Prins; Muhammad Riaz; Antonietta Robino; M Abdullah Said; Nicole Schupf; Robert A Scott; Tamar Sofer; Alena Stancáková; Fumihiko Takeuchi; Bamidele O Tayo; Peter J van der Most; Tibor V Varga; Tzung-Dau Wang; Yajuan Wang; Erin B Ware; Wanqing Wen; Yong-Bing Xiang; Lisa R Yanek; Weihua Zhang; Jing Hua Zhao; Adebowale Adeyemo; Saima Afaq; Najaf Amin; Marzyeh Amini; Dan E Arking; Zorayr Arzumanyan; Tin Aung; Christie Ballantyne; R Graham Barr; Lawrence F Bielak; Eric Boerwinkle; Erwin P Bottinger; Ulrich Broeckel; Morris Brown; Brian E Cade; Archie Campbell; Mickaël Canouil; Sabanayagam Charumathi; Yii-Der Ida Chen; Kaare Christensen; Maria Pina Concas; John M Connell; Lisa de Las Fuentes; H Janaka de Silva; Paul S de Vries; Ayo Doumatey; Qing Duan; Charles B Eaton; Ruben N Eppinga; Jessica D Faul; James S Floyd; Nita G Forouhi; Terrence Forrester; Yechiel Friedlander; Ilaria Gandin; He Gao; Mohsen Ghanbari; Sina A Gharib; Bruna Gigante; Franco Giulianini; Hans J Grabe; C Charles Gu; Tamara B Harris; Sami Heikkinen; Chew-Kiat Heng; Makoto Hirata; James E Hixson; M Arfan Ikram; Yucheng Jia; Roby Joehanes; Craig Johnson; Jost Bruno Jonas; Anne E Justice; Tomohiro Katsuya; Chiea Chuen Khor; Tuomas O Kilpeläinen; Woon-Puay Koh; Ivana Kolcic; Charles Kooperberg; Jose E Krieger; Stephen B Kritchevsky; Michiaki Kubo; Johanna Kuusisto; Timo A Lakka; Carl D Langefeld; Claudia Langenberg; Lenore J Launer; Benjamin Lehne; Cora E Lewis; Yize Li; Jingjing Liang; Shiow Lin; Ching-Ti Liu; Jianjun Liu; Kiang Liu; Marie Loh; Kurt K Lohman; Tin Louie; Anna Luzzi; Reedik Mägi; Anubha Mahajan; Ani W Manichaikul; Colin A McKenzie; Thomas Meitinger; Andres Metspalu; Yuri Milaneschi; Lili Milani; Karen L Mohlke; Yukihide Momozawa; Andrew P Morris; Alison D Murray; Mike A Nalls; Matthias Nauck; Christopher P Nelson; Kari E North; Jeffrey R O'Connell; Nicholette D Palmer; George J Papanicolau; Nancy L Pedersen; Annette Peters; Patricia A Peyser; Ozren Polasek; Neil Poulter; Olli T Raitakari; Alex P Reiner; Frida Renström; Treva K Rice; Stephen S Rich; Jennifer G Robinson; Lynda M Rose; Frits R Rosendaal; Igor Rudan; Carsten O Schmidt; Pamela J Schreiner; William R Scott; Peter Sever; Yuan Shi; Stephen Sidney; Mario Sims; Jennifer A Smith; Harold Snieder; John M Starr; Konstantin Strauch; Heather M Stringham; Nicholas Y Q Tan; Hua Tang; Kent D Taylor; Yik Ying Teo; Yih Chung Tham; Henning Tiemeier; Stephen T Turner; André G Uitterlinden; Diana van Heemst; Melanie Waldenberger; Heming Wang; Lan Wang; Lihua Wang; Wen Bin Wei; Christine A Williams; Gregory Wilson; Mary K Wojczynski; Jie Yao; Kristin Young; Caizheng Yu; Jian-Min Yuan; Jie Zhou; Alan B Zonderman; Diane M Becker; Michael Boehnke; Donald W Bowden; John C Chambers; Richard S Cooper; Ulf de Faire; Ian J Deary; Paul Elliott; Tõnu Esko; Martin Farrall; Paul W Franks; Barry I Freedman; Philippe Froguel; Paolo Gasparini; Christian Gieger; Bernardo L Horta; Jyh-Ming Jimmy Juang; Yoichiro Kamatani; Candace M Kammerer; Norihiro Kato; Jaspal S Kooner; Markku Laakso; Cathy C Laurie; I-Te Lee; Terho Lehtimäki; Patrik K E Magnusson; Albertine J Oldehinkel; Brenda W J H Penninx; Alexandre C Pereira; Rainer Rauramaa; Susan Redline; Nilesh J Samani; James Scott; Xiao-Ou Shu; Pim van der Harst; Lynne E Wagenknecht; Jun-Sing Wang; Ya Xing Wang; Nicholas J Wareham; Hugh Watkins; David R Weir; Ananda R Wickremasinghe; Tangchun Wu; Eleftheria Zeggini; Wei Zheng; Claude Bouchard; Michele K Evans; Vilmundur Gudnason; Sharon L R Kardia; Yongmei Liu; Bruce M Psaty; Paul M Ridker; Rob M van Dam; Dennis O Mook-Kanamori; Myriam Fornage; Michael A Province; Tanika N Kelly; Ervin R Fox; Caroline Hayward; Cornelia M van Duijn; E Shyong Tai; Tien Yin Wong; Ruth J F Loos; Nora Franceschini; Jerome I Rotter; Xiaofeng Zhu; Laura J Bierut; W James Gauderman Journal: Nat Genet Date: 2019-03-29 Impact factor: 41.307