Robust inference in summary data Mendelian randomization via the zero modal pleiotropy assumption

International Journal of Epidemiology
Fernando P HartwigJack Bowden

Abstract

Mendelian randomization (MR) is being increasingly used to strengthen causal inference in observational studies. Availability of summary data of genetic associations for a variety of phenotypes from large genome-wide association studies (GWAS) allows straightforward application of MR using summary data methods, typically in a two-sample design. In addition to the conventional inverse variance weighting (IVW) method, recently developed summary data MR methods, such as the MR-Egger and weighted median approaches, allow a relaxation of the instrumental variable assumptions. Here, a new method - the mode-based estimate (MBE) - is proposed to obtain a single causal effect estimate from multiple genetic instruments. The MBE is consistent when the largest number of similar (identical in infinite samples) individual-instrument causal effect estimates comes from valid instruments, even if the majority of instruments are invalid. We evaluate the performance of the method in simulations designed to mimic the two-sample summary data setting, and demonstrate its use by investigating the causal effect of plasma lipid fractions and urate levels on coronary heart disease risk. The MBE presented less bias and lower type-I error rates than other...Continue Reading

References

Apr 12, 2003·International Journal of Epidemiology·George Davey Smith, Shah Ebrahim
Apr 13, 2004·International Journal of Epidemiology·Duncan C Thomas, David V Conti
Oct 20, 2012·Statistics in Medicine·Roger M HarbordNuala A Sheehan
Dec 4, 2012·Nature Genetics·Panos DeloukasNilesh J Samani
Oct 8, 2013·Nature Genetics·Cristen WillerGlobal Lipids Genetics Consortium
Oct 12, 2013·Genetic Epidemiology·Stephen BurgessSimon G Thompson
Jul 30, 2014·Human Molecular Genetics·George Davey Smith, Gibran Hemani
Mar 17, 2015·European Journal of Epidemiology·Stephen BurgessEPIC- InterAct Consortium
May 8, 2015·Statistics in Medicine·Fabiola Del Greco MJohn R Thompson
Jun 8, 2015·International Journal of Epidemiology·Jack BowdenStephen Burgess
Jun 19, 2015·International Journal of Epidemiology·Stephen BurgessGeorge Davey Smith
Jan 20, 2016·The Lancet. Diabetes & Endocrinology·Jon WhiteUCLEB (University College London-London School of Hygiene & Tropical Medicine-Edinburgh-Bristol Consortium
Mar 11, 2016·The American Journal of Clinical Nutrition·P HaycockGeorge Davey Smith
Mar 25, 2017·International Journal of Epidemiology·Fernando P HartwigGeorge Davey Smith

Citations

Dec 12, 2017·Current Epidemiology Reports·J ZhengGeorge Davey Smith
Jul 5, 2018·Genetic Epidemiology·Fernando P HartwigGeorge Davey Smith
May 2, 2018·Annual Review of Genomics and Human Genetics·Stephen BurgessVerena Zuber
Oct 26, 2018·Obesity·Kaitlin H WadeNicholas J Timpson
Oct 31, 2018·Nature Genetics·Luke J O'Connor, Alkes L Price
Dec 28, 2018·Twin Research and Human Genetics : the Official Journal of the International Society for Twin Studies·Subhi Arafat, Camelia C Minică
Dec 21, 2018·Arteriosclerosis, Thrombosis, and Vascular Biology·Dipender GillMike Laffan
Jan 11, 2019·Ophthalmic & Physiological Optics : the Journal of the British College of Ophthalmic Opticians (Optometrists)·Denis Plotnikov, Jeremy A Guggenheim
Mar 13, 2019·Research Synthesis Methods·Jack Bowden, Michael V Holmes
Jun 28, 2019·International Journal of Epidemiology·Brandon Nick Sern OoiJingmei Li
Jun 28, 2019·BMJ : British Medical Journal·Rebecca C RichmondGeorge Davey Smith
Dec 19, 2017·International Journal of Epidemiology·Amand F Schmidt, Frank Dudbridge
Jul 3, 2018·International Journal of Epidemiology·Suzanne H GageMarcus R Munafò
Oct 25, 2019·Human Molecular Genetics·Neil M DaviesGeorge Davey Smith
Jan 10, 2020·Journal of the American Heart Association·Yuesong PanYongjun Wang
Feb 19, 2020·JAMA : the Journal of the American Medical Association·James YarmolinskyRichard M Martin
Jan 25, 2020·Annals of Neurology·Sandro MariniInternational Stroke Genetics Consortium
Mar 11, 2020·International Journal of Epidemiology·Camelia C MinicăMichael Neale
Mar 13, 2020·Journal of Bone and Mineral Research : the Official Journal of the American Society for Bone and Mineral Research·Jie ZhengDavid M Evans
Apr 7, 2020·Genetic Epidemiology·Eric A W Slob, Stephen Burgess
Apr 16, 2020·The British Journal of Psychiatry : the Journal of Mental Science·Ruth HarrisonRobyn E Wootton
Apr 25, 2020·Epidemiology and Psychiatric Sciences·Jesper Q ThomassenRuth Frikke-Schmidt
Feb 23, 2019·PloS One·Stacey S ChernyGregory Livshits
May 15, 2020·European Heart Journal·Jun LiLiming Liang
May 21, 2020·Blood Advances·Molly WentRichard S Houlston
Jun 25, 2020·American Journal of Medical Genetics. Part B, Neuropsychiatric Genetics : the Official Publication of the International Society of Psychiatric Genetics·Hannah J JonesStanley Zammit
Aug 12, 2020·Paediatric and Perinatal Epidemiology·Elizabeth W DiemerSonja A Swanson
Aug 8, 2020·International Journal of Cancer. Journal International Du Cancer·Nikos PapadimitriouKonstantinos K Tsilidis
Sep 7, 2019·Translational Psychiatry·Yuri MilaneschiBrenda W J H Penninx
Sep 12, 2020·International Journal of Cancer. Journal International Du Cancer·Wen ZhouChristopher I Amos
Sep 26, 2020·Journal of the American Heart Association·Joonatan PalmuTeemu J Niiranen
Oct 13, 2017·International Journal of Epidemiology·Jack Bowden
Apr 30, 2019·Royal Society Open Science·Rebecca B LawnMarcus R Munafò
May 31, 2019·Statistical Methods in Medical Research·Ioan Gabriel BucurTom Heskes
Oct 28, 2019·Frontiers in Neuroscience·Yuchang ZhouMaigeng Zhou
Nov 20, 2019·European Journal of Epidemiology·Li-Zhen LiaoXin-Xue Liao
Nov 21, 2019·Nature Communications·Laurence J HoweGibran Hemani
Dec 18, 2019·Korean Circulation Journal·Wes SpillerSun Ha Jee
Jan 23, 2020·Brain : a Journal of Neurology·Marios K GeorgakisMartin Dichgans
Mar 16, 2018·BMC Medicine·Linden Disney-HoggRichard S Houlston
Jun 7, 2018·Nature Reviews. Genetics·Jean-Baptiste PingaultFrank Dudbridge
Jul 31, 2018·International Journal of Epidemiology·Linda KachuriRayjean J Hung
Nov 22, 2018·International Journal of Epidemiology·Wes SpillerGeorge Davey Smith
Dec 12, 2018·Nature Communications·Aiden DohertyCecilia M Lindgren
Apr 20, 2019·International Journal of Obesity : Journal of the International Association for the Study of Obesity·Thais Martins-SilvaLuciana Tovo-Rodrigues
Jun 18, 2020·Diabetes, Metabolic Syndrome and Obesity : Targets and Therapy·Zefeng ChenZengnan Mo
Oct 2, 2020·Journal of the Royal Statistical Society. Series A, (Statistics in Society)·Marcus R MunafòGeorge Davey Smith
May 18, 2018·Human Molecular Genetics·Gibran HemaniGeorge Davey Smith
May 31, 2019·International Journal of Epidemiology·Niki DimouKonstantinos K Tsilidis
Feb 10, 2019·European Journal of Epidemiology·Siddhartha P KarPaul Pharoah
Aug 27, 2019·Wellcome Open Research·Venexia M WalkerRichard M Martin
May 6, 2019·JAMA Network Open·Renato PolimantiPsychiatric Genomics Consortium Posttraumatic Stress Disorder Working Group
Dec 12, 2019·Frontiers in Endocrinology·J ZhengJonathan H Tobias
Sep 19, 2019·The British Journal of Psychiatry : the Journal of Mental Science·Jentien M VermeulenMarcus R Munafò
Jun 13, 2020·Journal of Neurology·Marijne Vandebergh, An Goris
Aug 8, 2020·Wellcome Open Research·Stephen BurgessEvropi Theodoratou
Aug 28, 2020·Journal of Neurology, Neurosurgery, and Psychiatry·Sarah Opie-MartinAmmar Al-Chalabi
Jan 1, 2019·The American Journal of Clinical Nutrition·Dylan M WilliamsNancy L Pedersen
Feb 21, 2020·European Heart Journal·Milad NazarzadehKazem Rahimi
May 7, 2020·International Journal of Epidemiology·Christina DardaniGemma C Sharp
Apr 16, 2020·Frontiers in Genetics·Peng-Peng NiuYu-Ming Xu
Mar 20, 2018·International Journal of Obesity : Journal of the International Association for the Study of Obesity·Dipender GillCosetta Minelli
Jan 19, 2020·Nature Communications·Stephen BurgessJoanna M M Howson
Mar 11, 2020·Translational Psychiatry·Wikus BarkhuizenAngelica Ronald
Apr 23, 2020·Nature Communications·Yordi J van de VegteNiek Verweij
Sep 14, 2020·Neuropsychopharmacology : Official Publication of the American College of Neuropsychopharmacology·Danielle M AdamsMurray J Cairns
Aug 9, 2019·Osteoporosis International : a Journal Established As Result of Cooperation Between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the USA·A ZhouElina Hyppönen
Jun 2, 2017·Nature Reviews. Cardiology·Michael V HolmesGeorge Davey Smith
Oct 7, 2020·British Journal of Cancer·Charlie N SaundersCollaborators
Dec 9, 2020·Journal of the American Heart Association·M Abdullah SaidPim van der Harst
Dec 18, 2020·BMC Medicine·Caroline J BullMarc J Gunter
Dec 22, 2020·International Journal of Epidemiology·Gunn-Helen MoenNicole M Warrington
Jun 27, 2018·Cancer Epidemiology, Biomarkers & Prevention : a Publication of the American Association for Cancer Research, Cosponsored by the American Society of Preventive Oncology·James YarmolinskyRichard M Martin
Apr 6, 2019·Cancer Epidemiology, Biomarkers & Prevention : a Publication of the American Association for Cancer Research, Cosponsored by the American Society of Preventive Oncology·Upekha LiyanageStuart MacGregor
Aug 4, 2018·Cancer Epidemiology, Biomarkers & Prevention : a Publication of the American Association for Cancer Research, Cosponsored by the American Society of Preventive Oncology·Vanessa Y TanPRACTICAL consortium
Jan 6, 2021·Circulation. Cardiovascular Quality and Outcomes·Katy J L BellArmando Teixeira-Pinto
Jan 20, 2021·Nature Genetics·Alexander KurilshikovAlexandra Zhernakova
Jan 20, 2021·PloS One·Merete Ellingjord-DaleKonstantinos K Tsilidis
Jan 28, 2021·JAMA Network Open·Yongyue WeiDavid C Christiani
Apr 2, 2020·Cold Spring Harbor Perspectives in Medicine·Frank Dudbridge
Apr 29, 2020·Cold Spring Harbor Perspectives in Medicine·Eleanor Sanderson
Nov 15, 2020·Cancer Epidemiology, Biomarkers & Prevention : a Publication of the American Association for Cancer Research, Cosponsored by the American Society of Preventive Oncology·Sharayu MhatreRajesh P Dikshit
Feb 5, 2021·Stroke; a Journal of Cerebral Circulation·Eric L HarshfieldHugh S Markus
Jul 22, 2020·The Journal of Allergy and Clinical Immunology·Zhaozhong ZhuLiming Liang
Feb 12, 2021·International Journal of Epidemiology·Eleanor SandersonGeorge Davey Smith
Oct 30, 2020·Acta Neuropathologica Communications·Chenan ZhangKyle M Walsh
Jan 26, 2021·Clinical Nutrition : Official Journal of the European Society of Parenteral and Enteral Nutrition·Ang Zhou, Elina Hyppönen
Feb 16, 2021·Frontiers in Genetics·Ding YeYingying Mao
Dec 23, 2020·Nature Human Behaviour·Frank R WendtRenato Polimanti
Feb 26, 2021·PLoS Medicine·Despoina ManousakiJ Brent Richards
Mar 4, 2020·Cold Spring Harbor Perspectives in Medicine·Liang-Dar HwangDavid M Evans
Dec 16, 2020·Cancer Epidemiology, Biomarkers & Prevention : a Publication of the American Association for Cancer Research, Cosponsored by the American Society of Preventive Oncology·Aayah NounuCaroline L Relton
Mar 24, 2021·International Journal of Epidemiology·Lingling SunYingjun Li
Oct 16, 2018·Bone·Susanna C LarssonStephen Burgess
Mar 22, 2021·Alzheimer's & Dementia : the Journal of the Alzheimer's Association·Rainer MalikMartin Dichgans
Apr 4, 2021·Journal of Personalized Medicine·Yitang SunKaixiong Ye
Apr 5, 2021·Nutrition, Metabolism, and Cardiovascular Diseases : NMCD·Qi JiangMinglong Chen
Apr 27, 2021·International Journal of Epidemiology·Cosetta MinelliJohn Thompson
Apr 28, 2021·Stroke; a Journal of Cerebral Circulation·Jara Cárcel-MárquezIsrael Fernandez-Cadenas
Apr 21, 2021·Scientific Reports·Yordi J van de VegtePim van der Harst
Mar 27, 2021·The Journal of Clinical Endocrinology and Metabolism·Jiahao ZhuYingjun Li
Dec 9, 2020·Cold Spring Harbor Perspectives in Medicine·Tom G RichardsonTom R Gaunt
May 7, 2021·Journal of Bone and Mineral Research : the Official Journal of the American Society for Bone and Mineral Research·Hailuan ZengXin Gao
May 9, 2021·Cardiovascular Research·Emilie W KjeldsenRuth Frikke-Schmidt
Jun 8, 2021·International Journal of Epidemiology·Christina DardaniEvie Stergiakouli
Jun 9, 2021·International Journal of General Medicine·Yi HeJian-Rong Huang
Jun 5, 2021·Nutrition, Metabolism, and Cardiovascular Diseases : NMCD·Jiahao ZhuYingjun Li

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Spatio-Temporal Regulation of DNA Repair

DNA repair is a complex process regulated by several different classes of enzymes, including ligases, endonucleases, and polymerases. This feed focuses on the spatial and temporal regulation that accompanies DNA damage signaling and repair enzymes and processes.

Glut1 Deficiency

Glut1 deficiency, an autosomal dominant, genetic metabolic disorder associated with a deficiency of GLUT1, the protein that transports glucose across the blood brain barrier, is characterized by mental and motor developmental delays and infantile seizures. Follow the latest research on Glut1 deficiency with this feed.

Hereditary Sensory Autonomic Neuropathy

Hereditary Sensory Autonomic Neuropathies are a group of inherited neurodegenerative disorders characterized clinically by loss of sensation and autonomic dysfunction. Here is the latest research on these neuropathies.

Separation Anxiety

Separation anxiety is a type of anxiety disorder that involves excessive distress and anxiety with separation. This may include separation from places or people to which they have a strong emotional connection with. It often affects children more than adults. Here is the latest research on separation anxiety.

Neural Activity: Imaging

Imaging of neural activity in vivo has developed rapidly recently with the advancement of fluorescence microscopy, including new applications using miniaturized microscopes (miniscopes). This feed follows the progress in this growing field.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.