MRBEE: A novel bias-corrected multivariable Mendelian Randomization method
Mendelian randomization (MR) is an instrumental variable approach used to infer causal relationships between exposures and outcomes and can apply to summary data from genome-wide association studies (GWAS). Since GWAS summary statistics are subject to estimation errors, most existing MR approaches s...
Saved in:
| Published in | bioRxiv |
|---|---|
| Main Authors | , , , |
| Format | Journal Article Paper |
| Language | English |
| Published |
United States
Cold Spring Harbor Laboratory Press
12.06.2023
Cold Spring Harbor Laboratory |
| Edition | 1.3 |
| Subjects | |
| Online Access | Get full text |
| ISSN | 2692-8205 2692-8205 |
| DOI | 10.1101/2023.01.10.523480 |
Cover
| Abstract | Mendelian randomization (MR) is an instrumental variable approach used to infer causal relationships between exposures and outcomes and can apply to summary data from genome-wide association studies (GWAS). Since GWAS summary statistics are subject to estimation errors, most existing MR approaches suffer from measurement error bias, whose scale and direction are influenced by weak instrumental variables and GWAS sample overlap, respectively. We introduce MRBEE (MR using Bias-corrected Estimating Equation), a novel multivariable MR method capable of simultaneously removing measurement error bias and identifying horizontal pleiotropy. In simulations, we showed that MRBEE is capable of effectively removing measurement error bias in the presence of weak instrumental variables and sample overlap. In two independent real data analyses, we discovered that the causal effect of BMI on coronary artery disease risk is entirely mediated by blood pressure, and that existing MR methods may underestimate the causal effect of cannabis use disorder on schizophrenia risk compared to MRBEE. MRBEE possesses significant potential for advancing genetic research by providing a valuable tool to study causality between multiple risk factors and disease outcomes, particularly as a large number of GWAS summary statistics become publicly available. |
|---|---|
| AbstractList | Mendelian randomization (MR) is an instrumental variable approach used to infer causal relationships between exposures and outcomes and can apply to summary data from genome-wide association studies (GWAS). Since GWAS summary statistics are subject to estimation errors, most existing MR approaches suffer from measurement error bias, whose scale and direction are influenced by weak instrumental variables and GWAS sample overlap, respectively. We introduce MRBEE (MR using Bias-corrected Estimating Equation), a novel multivariable MR method capable of simultaneously removing measurement error bias and identifying horizontal pleiotropy. In simulations, we showed that MRBEE is capable of effectively removing measurement error bias in the presence of weak instrumental variables and sample overlap. In two independent real data analyses, we discovered that the causal effect of BMI on coronary artery disease risk is entirely mediated by blood pressure, and that existing MR methods may underestimate the causal effect of cannabis use disorder on schizophrenia risk compared to MRBEE. MRBEE possesses significant potential for advancing genetic research by providing a valuable tool to study causality between multiple risk factors and disease outcomes, particularly as a large number of GWAS summary statistics become publicly available.Mendelian randomization (MR) is an instrumental variable approach used to infer causal relationships between exposures and outcomes and can apply to summary data from genome-wide association studies (GWAS). Since GWAS summary statistics are subject to estimation errors, most existing MR approaches suffer from measurement error bias, whose scale and direction are influenced by weak instrumental variables and GWAS sample overlap, respectively. We introduce MRBEE (MR using Bias-corrected Estimating Equation), a novel multivariable MR method capable of simultaneously removing measurement error bias and identifying horizontal pleiotropy. In simulations, we showed that MRBEE is capable of effectively removing measurement error bias in the presence of weak instrumental variables and sample overlap. In two independent real data analyses, we discovered that the causal effect of BMI on coronary artery disease risk is entirely mediated by blood pressure, and that existing MR methods may underestimate the causal effect of cannabis use disorder on schizophrenia risk compared to MRBEE. MRBEE possesses significant potential for advancing genetic research by providing a valuable tool to study causality between multiple risk factors and disease outcomes, particularly as a large number of GWAS summary statistics become publicly available. Mendelian randomization (MR) is an instrumental variable approach used to infer causal relationships between exposures and outcomes and can apply to summary data from genome-wide association studies (GWAS). Since GWAS summary statistics are subject to estimation errors, most existing MR approaches suffer from measurement error bias, whose scale and direction are influenced by weak instrumental variables and GWAS sample overlap, respectively. We introduce MRBEE (MR using Bias-corrected Estimating Equation), a novel multivariable MR method capable of simultaneously removing measurement error bias and identifying horizontal pleiotropy. In simulations, we showed that MRBEE is capable of effectively removing measurement error bias in the presence of weak instrumental variables and sample overlap. In two independent real data analyses, we discovered that the causal effect of BMI on coronary artery disease risk is entirely mediated by blood pressure, and that existing MR methods may underestimate the causal effect of cannabis use disorder on schizophrenia risk compared to MRBEE. MRBEE possesses significant potential for advancing genetic research by providing a valuable tool to study causality between multiple risk factors and disease outcomes, particularly as a large number of GWAS summary statistics become publicly available. Mendelian Randomization (MR) has been widely applied to infer causality of exposures on outcomes in the genome wide association (GWAS) era. Existing approaches are often subject to biases from multiple sources including weak instruments, sample overlap, and measurement error. We introduce MRBEE, a computationally efficient multivariable MR method that can correct for all known biases simultaneously, which is demonstrated in theory, simulations, and real data analysis. In comparison, all existing MR methods are biased. In two independent real data analyses, we observed that the causal effect of BMI on coronary artery disease risk is completely mediated by blood pressure, and that existing MR methods drastically underestimate the causal effect of cannabis use disorder on schizophrenia risk compared to MRBEE. We demonstrate that MRBEE can be a useful tool in studying causality between multiple risk factors and a disease outcome, especially as more GWAS summary statistics are being made publicly available.Competing Interest StatementThe authors have declared no competing interest.Footnotes* https://github.com/noahlorinczcomi/MRBEE/blob/main/LorinczComi_etal_supp_data.xlsx |
| Author | Lorincz-Comi, Noah Yang, Yihe Zhu, Xiaofeng Li, Gen |
| Author_xml | – sequence: 1 givenname: Noah surname: Lorincz-Comi fullname: Lorincz-Comi, Noah organization: Case Western Reserve University, Cleveland, OH 44106, USA June 12, 2023 – sequence: 2 givenname: Yihe surname: Yang fullname: Yang, Yihe organization: Case Western Reserve University, Cleveland, OH 44106, USA June 12, 2023 – sequence: 3 givenname: Gen surname: Li fullname: Li, Gen organization: Case Western Reserve University, Cleveland, OH 44106, USA June 12, 2023 – sequence: 4 givenname: Xiaofeng surname: Zhu fullname: Zhu, Xiaofeng organization: Case Western Reserve University, Cleveland, OH 44106, USA June 12, 2023 |
| BackLink | https://www.ncbi.nlm.nih.gov/pubmed/37066391$$D View this record in MEDLINE/PubMed |
| BookMark | eNpdkEtLxEAMxwdRfKz7AbxIwYuXrkmmnXa86bK-UATRc5m2KY60M9rHon56K-sLT0ngxz_Jb0esO-9YiD2EGSLgEQHJGeBsnGOSUQprYpuUpjAliNf_9Fti2nVPAEBaoUyiTbElE1BKatwWVzd3p4vFcXASOL_kOsit6cLCty0XPZdBM9S9XZrWmrzm4IZdybU1LrgzrvSNfTe99S5ouH_05a7YqEzd8fSrTsTD2eJ-fhFe355fzk-uw5xQQYiYlhLyIimqnKiMNRMmkCidIFeRSVSELE2lQSudAjJKQtJFZQpdmjSN5UQcrnJz69tXu8yeW9uY9i37NJIBZgjZysgv-tz6l4G7PmtsV3BdG8d-6DJKgSKSKo5G9OAf-uSH1o2PZDTelKgUx9CJ2P-ihrzh8mf1t1D5Ac54ddE |
| ContentType | Journal Article Paper |
| Copyright | 2023. This article is published under http://creativecommons.org/licenses/by/4.0/ (“the License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License. 2023, Posted by Cold Spring Harbor Laboratory |
| Copyright_xml | – notice: 2023. This article is published under http://creativecommons.org/licenses/by/4.0/ (“the License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License. – notice: 2023, Posted by Cold Spring Harbor Laboratory |
| DBID | NPM 8FE 8FH ABUWG AFKRA AZQEC BBNVY BENPR BHPHI CCPQU DWQXO GNUQQ HCIFZ LK8 M7P PHGZM PHGZT PIMPY PKEHL PQEST PQGLB PQQKQ PQUKI PRINS 7X8 FX. |
| DOI | 10.1101/2023.01.10.523480 |
| DatabaseName | PubMed ProQuest SciTech Collection ProQuest Natural Science Collection ProQuest Central (Alumni) ProQuest Central UK/Ireland ProQuest Central Essentials Biological Science Collection ProQuest Central Natural Science Collection ProQuest One ProQuest Central Korea ProQuest Central Student SciTech Premium Collection Biological Sciences Biological Science Database ProQuest Central Premium ProQuest One Academic (New) Publicly Available Content Database ProQuest One Academic Middle East (New) ProQuest One Academic Eastern Edition (DO NOT USE) ProQuest One Applied & Life Sciences ProQuest One Academic ProQuest One Academic UKI Edition ProQuest Central China MEDLINE - Academic bioRxiv |
| DatabaseTitle | PubMed Publicly Available Content Database ProQuest Central Student ProQuest One Academic Middle East (New) ProQuest Biological Science Collection ProQuest Central Essentials ProQuest One Academic Eastern Edition ProQuest Central (Alumni Edition) SciTech Premium Collection ProQuest One Community College ProQuest Natural Science Collection Biological Science Database ProQuest SciTech Collection ProQuest Central China ProQuest Central ProQuest One Applied & Life Sciences ProQuest One Academic UKI Edition Natural Science Collection ProQuest Central Korea Biological Science Collection ProQuest Central (New) ProQuest One Academic ProQuest One Academic (New) MEDLINE - Academic |
| DatabaseTitleList | MEDLINE - Academic PubMed Publicly Available Content Database |
| Database_xml | – sequence: 1 dbid: FX. name: bioRxiv url: https://www.biorxiv.org/ sourceTypes: Open Access Repository – sequence: 2 dbid: NPM name: PubMed url: https://proxy.k.utb.cz/login?url=http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed sourceTypes: Index Database – sequence: 3 dbid: BENPR name: Proquest Central url: https://www.proquest.com/central sourceTypes: Aggregation Database |
| DeliveryMethod | fulltext_linktorsrc |
| Discipline | Biology |
| EISSN | 2692-8205 |
| Edition | 1.3 |
| ExternalDocumentID | 2023.01.10.523480v3 37066391 |
| Genre | Preprint Working Paper/Pre-Print |
| GrantInformation_xml | – fundername: NHGRI NIH HHS grantid: R01 HG011052 – fundername: NHLBI NIH HHS grantid: T32 HL007567 |
| GroupedDBID | NPM 8FE 8FH ABUWG AFKRA ALMA_UNASSIGNED_HOLDINGS AZQEC BBNVY BENPR BHPHI CCPQU DWQXO GNUQQ HCIFZ LK8 M7P NQS PHGZM PHGZT PIMPY PKEHL PQEST PQGLB PQQKQ PQUKI PRINS PROAC RHI 7X8 PUEGO FX. |
| ID | FETCH-LOGICAL-b2160-118d30bc7cfb22d59e217076971ef4a7641e3af90969801e132129cfac9da8853 |
| IEDL.DBID | FX. |
| ISSN | 2692-8205 |
| IngestDate | Tue Jan 07 18:53:20 EST 2025 Fri Sep 05 04:07:14 EDT 2025 Fri Jul 25 09:13:23 EDT 2025 Thu Apr 03 06:53:59 EDT 2025 |
| IsDoiOpenAccess | true |
| IsOpenAccess | true |
| IsPeerReviewed | false |
| IsScholarly | false |
| Keywords | Mendelian Randomization Statistical Genetics Complex Disease Genetic Epidemiology |
| Language | English |
| License | This pre-print is available under a Creative Commons License (Attribution 4.0 International), CC BY 4.0, as described at http://creativecommons.org/licenses/by/4.0 |
| LinkModel | DirectLink |
| MergedId | FETCHMERGED-LOGICAL-b2160-118d30bc7cfb22d59e217076971ef4a7641e3af90969801e132129cfac9da8853 |
| Notes | SourceType-Working Papers-1 ObjectType-Working Paper/Pre-Print-1 content type line 50 ObjectType-Article-2 SourceType-Scholarly Journals-1 ObjectType-Feature-3 content type line 23 Competing Interest Statement: The authors have declared no competing interest. |
| ORCID | 0000-0003-0037-411X 0000-0001-6563-3579 0000-0002-6337-3029 0000-0002-0517-2499 |
| OpenAccessLink | https://www.biorxiv.org/content/10.1101/2023.01.10.523480 |
| PMID | 37066391 |
| PQID | 2764768152 |
| PQPubID | 2050091 |
| PageCount | 32 |
| ParticipantIDs | biorxiv_primary_2023_01_10_523480 proquest_miscellaneous_2802423654 proquest_journals_2764768152 pubmed_primary_37066391 |
| PublicationCentury | 2000 |
| PublicationDate | 2023-Jun-12 |
| PublicationDateYYYYMMDD | 2023-06-12 |
| PublicationDate_xml | – month: 06 year: 2023 text: 2023-Jun-12 day: 12 |
| PublicationDecade | 2020 |
| PublicationPlace | United States |
| PublicationPlace_xml | – name: United States – name: Cold Spring Harbor |
| PublicationTitle | bioRxiv |
| PublicationTitleAlternate | bioRxiv |
| PublicationYear | 2023 |
| Publisher | Cold Spring Harbor Laboratory Press Cold Spring Harbor Laboratory |
| Publisher_xml | – name: Cold Spring Harbor Laboratory Press – name: Cold Spring Harbor Laboratory |
| References | 38582968 - HGG Adv. 2024 Apr 6;:100290 Savitz, Van Der Merwe, Solms, Ramesar (2023.01.10.523480v3.42) 2007; 6 Okbay, Wu, Wang, Jayashankar, Bennett, Nehzati, Sidorenko, Kweon, Goldman, Gjorgjieva (2023.01.10.523480v3.33) 2022; 54 Grant, Burgess (2023.01.10.523480v3.23) 2021; 40 Burgess, Bowden (2023.01.10.523480v3.6) 2015 Wang, Shi, Zhu, Hao, Chen, Cheng, Foo, Wang (2023.01.10.523480v3.49) 2022; 14 Bowden, Smith, Haycock, Burgess (2023.01.10.523480v3.4) 2016; 40 Ishigaki, Akiyama, Kanai, Takahashi, Kawakami, Sugishita, Sakaue, Matoba, Low, Okada (2023.01.10.523480v3.25) 2020; 52 Verbanck, Chen, Neale, Do (2023.01.10.523480v3.48) 2018; 50 Pasman, Demange, Guloksuz, Willemsen, Abdellaoui, Ten Have, Hottenga, Boomsma, de Geus, Bartels (2023.01.10.523480v3.34) 2022; 52 Xue, Shen, Pan (2023.01.10.523480v3.51) 2021; 108 van Der Graaf, Claringbould, Rimbert, van Meurs Joyce, Rick, Lude, Westra, Li, Wijmenga, Sanna (2023.01.10.523480v3.46) 2020; 11 Mounier, Kutalik (2023.01.10.523480v3.30) 2023 Qi, Chatterjee (2023.01.10.523480v3.35) 2019; 10 Lawlor, Harbord, Sterne, Timpson, Smith (2023.01.10.523480v3.27) 2008; 27 Yang, Lorincz-Comi, Zhu (2023.01.10.523480v3.52) 2023 Marconi, Di Forti, Lewis, Murray, Vassos (2023.01.10.523480v3.28) 2016; 42 Aragam, Jiang, Goel, Kanoni, Wolford, Atri, Weeks, Wang, Hindy, Zhou (2023.01.10.523480v3.1) 2022 Burgess, Foley, Allara, Staley, Howson (2023.01.10.523480v3.9) 2020; 11 Yavorska, Burgess (2023.01.10.523480v3.53) 2017; 46 Burgess, Thompson (2023.01.10.523480v3.11) 2015; 181 Trubetskoy, Pardinñas, Qi, Panagiotaropoulou, Awasthi, Bigdeli, Bryois, Chen, Dennison, Hall (2023.01.10.523480v3.45) 2022; 604 Rees, Wood, Dudbridge, Burgess (2023.01.10.523480v3.37) 2019; 14 Kang, Zhang, Cai, Small (2023.01.10.523480v3.26) 2016; 111 Brumpton, Sanderson, Heilbron, Hartwig, Harrison, Vie, Cho, Howe, Hughes, Boomsma (2023.01.10.523480v3.5) 2020; 11 Cheng, Zhang, Chen, Liu (2023.01.10.523480v3.17) 2022; 13 Fairley, Lowy-Gallego, Perry, Flicek (2023.01.10.523480v3.20) 2020; 48 Hartwig, Davies, Smith (2023.01.10.523480v3.24) 2018; 42 Baranzini, Wang, Gibson, Galwey, Naegelin, Barkhof, Radue, Lindberg, Uitdehaag, Johnson (2023.01.10.523480v3.2) 2009; 18 Burgess, Thompson, Collaboration (2023.01.10.523480v3.12) 2011; 40 Cuellar-Partida, Tung, Eriksson, Albrecht, Aliev, Andreassen, Barroso, Beckmann, Boks, Boomsma (2023.01.10.523480v3.18) 2021; 5 Słomian, Szyda, Dobosz, Stojak, Michalska-Foryszewska, Sypniewski, Liu, Kotlarz, Suchocki, Mroczek (2023.01.10.523480v3.44) 2023; 18 Burgess, Smith, Davies, Dudbridge, Gill, Glymour, Hartwig, Holmes, Minelli, Relton (2023.01.10.523480v3.10) 2019; 4 Zhu, Feng, Tayo, Liang, Young, Franceschini, Smith, Yanek, Sun, Edwards (2023.01.10.523480v3.58) 2015; 96 Sanderson, Spiller, Bowden (2023.01.10.523480v3.41) 2021; 40 Cheng, Qiu, Chai, Sun, Xia, Shi, Liu (2023.01.10.523480v3.16) 2022; 38 Gilbody, Borges, Smith, Sanderson (2023.01.10.523480v3.21) 2022 Ye, Shao, Kang (2023.01.10.523480v3.54) 2021; 49 Sanderson, Smith, Windmeijer, Bowden (2023.01.10.523480v3.39) 2019; 48 Yi (2023.01.10.523480v3.56) 2017 Burgess, Butterworth, Thompson (2023.01.10.523480v3.7) 2013; 37 Chang, Chow, Tellier, Vattikuti, Purcell, Lee (2023.01.10.523480v3.15) 2015; 4 Sanderson, Glymour, Holmes, Kang, Morrison, Munafó, Palmer, Schooling, Wallace, Zhao (2023.01.10.523480v3.40) 2022; 2 Scully, Owens, Kinsella, Waddington (2023.01.10.523480v3.43) 2000; 12 Zhu, Li, Xu, Wang (2023.01.10.523480v3.59) 2021; 37 Burgess, Davies, Thompson (2023.01.10.523480v3.8) 2016; 40 Morrison, Knoblauch, Marcus, Stephens, He (2023.01.10.523480v3.29) 2020; 52 Zhu, Zhu, Wang, Cooper, Chakravarti (2023.01.10.523480v3.60) 2022; 46 Bellani, Marzi, Savazzi, Perlini, Cerruti, Ferro, Marinelli, Sponda, Rambaldelli, Tansella (2023.01.10.523480v3.3) 2010; 201 Zhu (2023.01.10.523480v3.57) 2020 Nagai, Hirata, Kamatani, Muto, Matsuda, Kiyohara, Ninomiya, Tamakoshi, Yamagata, Mushiroda (2023.01.10.523480v3.32) 2017; 27 Burgess, Timpson, Ebrahim, Smith (2023.01.10.523480v3.13) 2015 Mullins, Forstner, O’Connell, Coombes, Coleman, Qiao, Als, Bigdeli, Børte, Bryois (2023.01.10.523480v3.31) 2021; 53 Gill, Georgakis, Walker, Schmidt, Gkatzionis, Freitag, Finan, Hingorani, Howson, Burgess (2023.01.10.523480v3.22) 2021; 6 Yengo, Vedantam, Marouli, Sidorenko, Bartell, Sakaue, Graff, Eliasen, Jiang, Raghavan (2023.01.10.523480v3.55) 2022; 610 (2023.01.10.523480v3.14) 2015; 47 VanderWeele, Tchetgen, Cornelis, Kraft (2023.01.10.523480v3.47) 2014; 25 Welch, Ley, Link, Miller, Larson, Koboldt, Wartman, Lamprecht, Liu, Xia (2023.01.10.523480v3.50) 2012; 150 Sadreev, Elsworth, Mitchell, Paternoster, Sanderson, Davies, Millard, Smith, Haycock, Bowden (2023.01.10.523480v3.38) 2021 Demontis, Walters, Martin, Mattheisen, Als, Agerbo, Baldursson, Belliveau, Bybjerg-Grauholm, Bækvad-Hansen (2023.01.10.523480v3.19) 2019; 51 Rees, Wood, Burgess (2023.01.10.523480v3.36) 2017; 36 |
| References_xml | – reference: 38582968 - HGG Adv. 2024 Apr 6;:100290 – volume: 37 start-page: 1390 issue: 10 year: 2021 end-page: 1400 ident: 2023.01.10.523480v3.59 article-title: An iterative approach to detect pleiotropy and perform mendelian randomization analysis using gwas summary statistics publication-title: Bioinformatics – volume: 46 start-page: 105 issue: 2 year: 2022 end-page: 121 ident: 2023.01.10.523480v3.60 article-title: Genome-wide pleiotropy analysis identifies novel blood pressure variants and improves its polygenic risk scores publication-title: Genet. Epidemiol – volume: 610 start-page: 704 issue: 7933 year: 2022 end-page: 712 ident: 2023.01.10.523480v3.55 article-title: A saturated map of common genetic variants associated with human height publication-title: Nature – volume: 2 start-page: 1 issue: 1 year: 2022 end-page: 21 ident: 2023.01.10.523480v3.40 article-title: Mendelian randomization.\ publication-title: Nat. Rev. Methods Primers – volume: 46 start-page: 1734 issue: 6 year: 2017 end-page: 1739 ident: 2023.01.10.523480v3.53 article-title: Mendelianrandomization: an r package for performing mendelian randomization analyses using summarized data publication-title: Int. J. Epidemiol – volume: 49 start-page: 2079 issue: 4 year: 2021 end-page: 2100 ident: 2023.01.10.523480v3.54 article-title: Debiased inverse-variance weighted estimator in two-sample summary-data mendelian randomization publication-title: Ann. Stat – volume: 52 start-page: 92 issue: 2 year: 2022 end-page: 107 ident: 2023.01.10.523480v3.34 article-title: Genetic risk for smoking: disentangling interplay between genes and socioeconomic status publication-title: Behavior Genetics – volume: 12 start-page: 73 issue: 3 year: 2000 end-page: 76 ident: 2023.01.10.523480v3.43 article-title: Epidemiology and patho-biology of bipolar disorder, and their exploration within a complete catchment area population publication-title: Acta Neuropsychiatrica – year: 2022 ident: 2023.01.10.523480v3.21 article-title: Multivariable mr can mitigate bias in two-sample mr using covariable-adjusted summary associations publication-title: medRxiv – year: 2017 ident: 2023.01.10.523480v3.56 publication-title: Statistical analysis with measurement error or misclassification: strategy, method and application – volume: 51 start-page: 63 issue: 1 year: 2019 end-page: 75 ident: 2023.01.10.523480v3.19 article-title: Discovery of the first genome-wide significant risk loci for attention deficit/hyperactivity disorder publication-title: Nature Genetics – volume: 14 start-page: e0222362 issue: 9 year: 2019 ident: 2023.01.10.523480v3.37 article-title: Robust methods in mendelian randomization via penalization of heterogeneous causal estimates publication-title: PloS One – volume: 54 start-page: 437 issue: 4 year: 2022 end-page: 449 ident: 2023.01.10.523480v3.33 article-title: Polygenic prediction of educational attainment within and between families from genome-wide association analyses in 3 million individuals publication-title: Nature Genetics – volume: 18 start-page: 767 issue: 4 year: 2009 end-page: 778 ident: 2023.01.10.523480v3.2 article-title: Genome-wide association analysis of susceptibility and clinical phenotype in multiple sclerosis publication-title: Human Molecular Genetics – year: 2015 ident: 2023.01.10.523480v3.6 article-title: Integrating summarized data from multiple genetic variants in mendelian randomization: bias and coverage properties of inverse-variance weighted methods publication-title: arXiv – volume: 52 start-page: 669 issue: 7 year: 2020 end-page: 679 ident: 2023.01.10.523480v3.25 article-title: Large-scale genome-wide association study in a japanese population identifies novel susceptibility loci across different diseases publication-title: Nature Genetics – volume: 25 start-page: 427 issue: 3 year: 2014 ident: 2023.01.10.523480v3.47 article-title: Methodological challenges in mendelian randomization publication-title: Epidemiology – volume: 4 year: 2019 ident: 2023.01.10.523480v3.10 article-title: Guidelines for performing mendelian randomization investigations publication-title: Wellcome Open Research – volume: 40 start-page: 5813 issue: 26 year: 2021 end-page: 5830 ident: 2023.01.10.523480v3.23 article-title: Pleiotropy robust methods for multivariable mendelian randomization publication-title: Stat. Med – year: 2021 ident: 2023.01.10.523480v3.38 article-title: Navigating sample overlap, winner’s curse and weak instrument bias in mendelian randomization studies using the uk biobank publication-title: medRxiv – volume: 52 start-page: 740 issue: 7 year: 2020 end-page: 747 ident: 2023.01.10.523480v3.29 article-title: Mendelian randomization accounting for correlated and uncorrelated pleiotropic effects using genome-wide summary statistics publication-title: Nat. Genet – volume: 10 start-page: 1 issue: 1 year: 2019 end-page: 10 ident: 2023.01.10.523480v3.35 article-title: Mendelian randomization analysis using mixture models for robust and efficient estimation of causal effects publication-title: Nat. Commun – volume: 40 start-page: 5434 issue: 25 year: 2021 end-page: 5452 ident: 2023.01.10.523480v3.41 article-title: Testing and correcting for weak and pleiotropic instruments in two-sample multivariable mendelian randomization publication-title: Stat. Med – volume: 150 start-page: 264 issue: 2 year: 2012 end-page: 278 ident: 2023.01.10.523480v3.50 article-title: The origin and evolution of mutations in acute myeloid leukemia publication-title: Cell – volume: 5 start-page: 59 issue: 1 year: 2021 end-page: 70 ident: 2023.01.10.523480v3.18 article-title: Genome-wide association study identifies 48 common genetic variants associated with handedness publication-title: Nature Human Behaviour – volume: 37 start-page: 658 issue: 7 year: 2013 end-page: 665 ident: 2023.01.10.523480v3.7 article-title: Mendelian randomization analysis with multiple genetic variants using summarized data publication-title: Genet. Epidemiol – volume: 111 start-page: 132 issue: 513 year: 2016 end-page: 144 ident: 2023.01.10.523480v3.26 article-title: Instrumental variables estimation with some invalid instruments and its application to mendelian randomization publication-title: J. Am. Stat. Assoc – year: 2023 ident: 2023.01.10.523480v3.52 article-title: Unbiased estimation and asymptotically valid inference in multivariable mendelian randomization with many weak instrumental variables publication-title: arXiv – start-page: 1 year: 2022 end-page: 13 ident: 2023.01.10.523480v3.1 article-title: Discovery and systematic characterization of risk variants and genes for coronary artery disease in over a million participants publication-title: Nature Genetics – volume: 38 start-page: 303 issue: 2 year: 2022 end-page: 310 ident: 2023.01.10.523480v3.16 article-title: Mr-corr2: a two-sample mendelian randomization method that accounts for correlated horizontal pleiotropy using correlated instrumental variants publication-title: Bioinformatics – volume: 48 start-page: D941 issue: D1 year: 2020 end-page: D947 ident: 2023.01.10.523480v3.20 article-title: The international genome sample resource (igsr) collection of open human genomic variation resources publication-title: Nucleic Acids Research – volume: 27 start-page: S2 issue: Supplement III year: 2017 end-page: S8 ident: 2023.01.10.523480v3.32 article-title: Overview of the biobank japan project: study design and profile publication-title: Int. J. Epidemiol – volume: 96 start-page: 21 issue: 1 year: 2015 end-page: 36 ident: 2023.01.10.523480v3.58 article-title: Meta-analysis of correlated traits via summary statistics from gwass with an application in hypertension publication-title: Am. J. Hum. Genet – volume: 108 start-page: 1251 issue: 7 year: 2021 end-page: 1269 ident: 2023.01.10.523480v3.51 article-title: Constrained maximum likelihood-based mendelian randomization robust to both correlated and uncorrelated pleiotropic effects publication-title: Am. J. Hum. Genet – volume: 181 start-page: 251 issue: 4 year: 2015 end-page: 260 ident: 2023.01.10.523480v3.11 article-title: Multivariable mendelian randomization: the use of pleiotropic genetic variants to estimate causal effects publication-title: American Int. J. Epi-demiol – volume: 50 start-page: 693 issue: 5 year: 2018 end-page: 698 ident: 2023.01.10.523480v3.48 article-title: Detection of widespread horizontal pleiotropy in causal relationships inferred from mendelian randomization between complex traits and diseases publication-title: Nat. Genet – volume: 36 start-page: 4705 issue: 29 year: 2017 end-page: 4718 ident: 2023.01.10.523480v3.36 article-title: Extending the mr-egger method for multivariable mendelian randomization to correct for both measured and unmeasured pleiotropy publication-title: Stat. Med – year: 2023 ident: 2023.01.10.523480v3.30 article-title: Bias correction for inverse variance weighting mendelian randomization publication-title: Genetic Epidemiology – volume: 4 start-page: s13742 issue: 1 year: 2015 end-page: 015 ident: 2023.01.10.523480v3.15 article-title: Second-generation plink: rising to the challenge of larger and richer datasets publication-title: Giga-science – volume: 11 start-page: 1 issue: 1 year: 2020 end-page: 11 ident: 2023.01.10.523480v3.9 article-title: A robust and efficient method for mendelian randomization with hundreds of genetic variants publication-title: Nat. Commun – volume: 40 start-page: 304 issue: 4 year: 2016 end-page: 314 ident: 2023.01.10.523480v3.4 article-title: Consistent estimation in mendelian randomization with some invalid instruments using a weighted median estimator publication-title: Genet. Epidemiol – volume: 11 start-page: 4930 issue: 1 year: 2020 ident: 2023.01.10.523480v3.46 article-title: Mendelian randomization while jointly modeling cis genetics identifies causal relationships between gene expression and lipids publication-title: Nature Communications – volume: 42 start-page: 1262 issue: 5 year: 2016 end-page: 1269 ident: 2023.01.10.523480v3.28 article-title: Meta-analysis of the association between the level of cannabis use and risk of psychosis publication-title: Schizophrenia Bulletin – volume: 40 start-page: 597 issue: 7 year: 2016 end-page: 608 ident: 2023.01.10.523480v3.8 article-title: Bias due to participant overlap in two-sample mendelian randomization publication-title: Genet. Epidemiol – year: 2015 ident: 2023.01.10.523480v3.13 publication-title: Mendelian randomization: where are we now and where are we going? – volume: 48 start-page: 713 issue: 3 year: 2019 end-page: 727 ident: 2023.01.10.523480v3.39 article-title: An examination of multivariable mendelian randomization in the single-sample and two-sample summary data settings publication-title: Int. J. Epidemiol – volume: 18 start-page: e0279356 issue: 1 year: 2023 ident: 2023.01.10.523480v3.44 article-title: Better safe than sorry—whole-genome sequencing indicates that missense variants are significant in susceptibility to covid-19 publication-title: PloS One – volume: 53 start-page: 817 issue: 6 year: 2021 end-page: 829 ident: 2023.01.10.523480v3.31 article-title: Genome-wide association study of more than 40,000 bipolar disorder cases provides new insights into the underlying biology publication-title: Nature Genetics – volume: 14 start-page: 1 issue: 1 year: 2022 end-page: 15 ident: 2023.01.10.523480v3.49 article-title: Mendelian randomization analysis of 37 clinical factors and coronary artery disease in east asian and european populations publication-title: Genome Medicine – volume: 40 start-page: 755 issue: 3 year: 2011 end-page: 764 ident: 2023.01.10.523480v3.12 article-title: Avoiding bias from weak instruments in mendelian randomization studies publication-title: Int. J. Epidemiol – volume: 6 year: 2021 ident: 2023.01.10.523480v3.22 article-title: Mendelian randomization for studying the effects of perturbing drug targets publication-title: Wellcome Open Research – volume: 6 start-page: 698 issue: 8 year: 2007 end-page: 705 ident: 2023.01.10.523480v3.42 article-title: Lateralization of hand skill in bipolar affective disorder publication-title: Genes, Brain and Behavior – volume: 604 start-page: 502 issue: 7906 year: 2022 end-page: 508 ident: 2023.01.10.523480v3.45 article-title: Mapping genomic loci implicates genes and synaptic biology in schizophrenia publication-title: Nature – volume: 201 start-page: 339 year: 2010 end-page: 344 ident: 2023.01.10.523480v3.3 article-title: Laterality effects in schizophrenia and bipolar disorder publication-title: Experimental Brain Research – volume: 47 start-page: 1121 issue: 10 year: 2015 end-page: 1130 ident: 2023.01.10.523480v3.14 article-title: A comprehensive 1000 genomes–based genome-wide association meta-analysis of coronary artery disease publication-title: Nature Genetics – volume: 42 start-page: 608 issue: 7 year: 2018 end-page: 620 ident: 2023.01.10.523480v3.24 article-title: Bias in mendelian randomization due to assortative mating publication-title: Genetic Epidemiology – start-page: 1 year: 2020 end-page: 11 ident: 2023.01.10.523480v3.57 article-title: Mendelian randomization and pleiotropy analysis publication-title: Quant. Biol – volume: 13 start-page: 1 issue: 1 year: 2022 end-page: 13 ident: 2023.01.10.523480v3.17 article-title: Mendelian randomization accounting for complex correlated horizontal pleiotropy while elucidating shared genetic etiology publication-title: Nat. Commun – volume: 11 start-page: 3519 issue: 1 year: 2020 ident: 2023.01.10.523480v3.5 article-title: Avoiding dynastic, assortative mating, and population stratification biases in mendelian randomization through within-family analyses publication-title: Nature Communications – volume: 27 start-page: 1133 issue: 8 year: 2008 end-page: 1163 ident: 2023.01.10.523480v3.27 article-title: Mendelian randomization: using genes as instruments for making causal inferences in epidemiology publication-title: Statistics in medicine |
| SSID | ssj0002961374 |
| Score | 1.8368075 |
| SecondaryResourceType | preprint |
| Snippet | Mendelian randomization (MR) is an instrumental variable approach used to infer causal relationships between exposures and outcomes and can apply to summary... Mendelian Randomization (MR) has been widely applied to infer causality of exposures on outcomes in the genome wide association (GWAS) era. Existing approaches... |
| SourceID | biorxiv proquest pubmed |
| SourceType | Open Access Repository Aggregation Database Index Database |
| SubjectTerms | Blood pressure Cannabis Cardiovascular disease Coronary artery disease Genomes Genomics Heart diseases Mental disorders Risk factors Schizophrenia Statistical analysis |
| SummonAdditionalLinks | – databaseName: ProQuest Central dbid: BENPR link: http://utb.summon.serialssolutions.com/2.0.0/link/0/eLvHCXMwfV3dS8MwEA-6MfDNb6dTKvga7EfaNL6Ik44x2BjDwd5K0qQw0HbuC_3vvWuz-aSPpSEtv15z97vk7kfIA_dErmWoKNNYkhNyRmMWSxqoSEZMyIAZLHAejqL-lA1m4cwm3Fb2WOVuTawWal1mmCN_9HnEIDQGd_O8-KSoGoW7q1ZC45A0YQmOwc6b3WQ0nuyzLL4Ad1W1YvYjAb--74Z2axNMEYl_gE074Rr4GMPWkC01L5df8-3fAWfleHrHpDmWC7M8IQemOCWtWjny-4wMhpNukjw5L05Rbs27o-ZyRTNU2sgghHSqY4JboMFYGOUMMc2N6QxnIgtdftjSS6dWjz4n017y9tqnVhaBKt-LXAqUQAeuyniWK9_XoTBAK1weCe6ZnEnAyTOBzAWQEwH-xwDfBKee5TITWsbgni9IoygLc0Ucif3-Yh1qTzAWwHDla4Ah9wyXyo15m9xbPNJF3fwiRcxS10uBPNSYtUlnh1Rq7X-V_n4tmGJ_GywXtyNkYcoNjIkxPgiikLXJZY3w_ikBx1BIeNf_T35DjvB9aKUl1CGN9XJjbiFIWKs7awk_0WG1zA priority: 102 providerName: ProQuest |
| Title | MRBEE: A novel bias-corrected multivariable Mendelian Randomization method |
| URI | https://www.ncbi.nlm.nih.gov/pubmed/37066391 https://www.proquest.com/docview/2764768152 https://www.proquest.com/docview/2802423654 https://www.biorxiv.org/content/10.1101/2023.01.10.523480 |
| hasFullText | 1 |
| inHoldings | 1 |
| isFullTextHit | |
| isPrint | |
| link | http://utb.summon.serialssolutions.com/2.0.0/link/0/eLvHCXMwjV3fS8MwEA7iEHzzt9M5Ivgaadq0aXxzsjEGHWM42FtJmhQG2o79Qv9779o6fFDwpdA2bcJx7X3fJZePkAfJVW51aJiwWJITSsFiEWsWmEhHQulAOCxwTsbRcCZG83D-Q-oLl1WaRbn6WOyqeXxcsA1_3_rj9jhy9QD32YRzoFAiBrbeApfyUbVhMH_cp1d8BXFKimYe89cnAfE2Pf2NLqsoMzghrYleutUpOXDFGTmqZSI_z8komfb6_Sf6TIty596oWeg1y1BWIwO8SKs1gTvgvFgFRRPMaWPugk51Ycv3ps6S1lLRF2Q26L--DFmjgcCMzyOPAf63gWcymeXG922oHHAIT0ZKcpcLLSPBXaBzBUxEQbBxQC4hgme5zpTVMcTiS3JYlIW7JlTj5n6xDS1XQgTQ3PgWzJBzJ7XxYtkm94090mW900WKNks9ngJTqG3WJp1vS6WNs69TH0YBrAWQALxifxvcFOcedOHKLbSJEQwEUSja5Kq28L6XQCLuUfzmHwO4Jcd4jVXqQR1yuFlt3R3Ago3pklavP55Mu5UjwHE8Sb4As7Ww4A |
| linkProvider | Cold Spring Harbor Laboratory Press |
| linkToHtml | http://utb.summon.serialssolutions.com/2.0.0/link/0/eLvHCXMwtV3dT9swED-hVoi9wWCsDDYjsUeLxHE-jDQh2IrKRytUgcRbsGNHqrQlXVsK_FP7G7lL0u4J3niMYtnR5Xz3u7PvfgAHsa9yq0PDpaWSnDCWPJGJ5oGJdCSVDqSjAuf-IOrdyou78G4F_i1qYeha5cImVobalhnlyA9FHEmExuhujsd_ObFG0enqgkKjVotL9_yIIdv0x_kv_L_fhTjr3vzs8YZVgBvhRx5HRG0Dz2RxlhshbKgconKM5lXsu1xqXMZ3gc4VYnuF5tthuIY-Mct1pqxOEmKJQJPfllTR2oL2aXdwPVxmdYRC91i1fhaRQlMjvLA5SkXVp0RDQE1C8RnjP0mtKFfNqJw8jeavA9zK0Z2tQ_taj91kA1Zc8RFWa6bK50246A9Pu90jdsKKcu5-MzPSU54Rs0eGkJVV1xLnGHZTIRbrU1qd0idsqAtb_mlKPVnNVr0Ft-8isE_QKsrCfQamqb9gYkPrKykDHG6ERTHkvou18ZK4A_uNPNJx3WwjJZmlnp9isFLLrAO7C0mlzX6bpv-1A6dYvsadQscfunDlA45JCI8EUSg7sF1LeLlKEBP0Uv7O25N_g7XeTf8qvTofXH6BD_RtvOIx2oXWbPLg9hCgzMzXRisY3L-3Ir4AZSTw3w |
| linkToPdf | http://utb.summon.serialssolutions.com/2.0.0/link/0/eLvHCXMwjV1bS8MwFA66ofjm3enUCr5mNG3aNL552ZjTjTEU9laSJoWBtmM39N97TluHDwo-loQkHE56vu_kXAi5FkymRgWacoMpOYHgNOKRor4OVcil8rnFBOf-IOy-8t44GP_IhcGwSj3JZx-TVfGOjwHb8PctL7fLkKv7WGcTvoFC8chtoZu6NTXpJqmDbjHU7M64tfazeBIMluDVg-avSwD0rbb8G2YW5qazS-pDNbWzPbJhs32yVfaL_Dwgvf7ort2-cW6dLF_ZN0dP1Jwm2F8jAeDoFMGBKyC_mA7l9NG5jU4MZ6Qyk79XCZdO2TP6kLx22i_3XVo1Q6DaY6FLgQgY39WJSFLteSaQFsiEK0IpmE25EiFn1lepBEoiwepYYJlgypNUJdKoCIzyEalleWZPiKOwyl9kAsMk5z5M154BMaTMCqXdSDTIVSWPeFqWvIhRZrHLYqAMpcwapPktqbjS-nnswSmAvgAkgCXWw6Cv-AihMpsvYU6EqMAPA94gx6WE17v4AgGQZKf_OMAl2R4-dOLnx8HTGdnBYVp0FGqS2mK2tOcAFRb6otCFL9W4tCI |
| openUrl | ctx_ver=Z39.88-2004&ctx_enc=info%3Aofi%2Fenc%3AUTF-8&rfr_id=info%3Asid%2Fsummon.serialssolutions.com&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=MRBEE%3A+A+novel+bias-corrected+multivariable+Mendelian+Randomization+method&rft.jtitle=bioRxiv&rft.au=Lorincz-Comi%2C+Noah&rft.au=Yang%2C+Yihe&rft.au=Li%2C+Gen&rft.au=Zhu%2C+Xiaofeng&rft.date=2023-06-12&rft.issn=2692-8205&rft.eissn=2692-8205&rft_id=info:doi/10.1101%2F2023.01.10.523480&rft.externalDBID=NO_FULL_TEXT |
| thumbnail_l | http://covers-cdn.summon.serialssolutions.com/index.aspx?isbn=/lc.gif&issn=2692-8205&client=summon |
| thumbnail_m | http://covers-cdn.summon.serialssolutions.com/index.aspx?isbn=/mc.gif&issn=2692-8205&client=summon |
| thumbnail_s | http://covers-cdn.summon.serialssolutions.com/index.aspx?isbn=/sc.gif&issn=2692-8205&client=summon |