دورية أكاديمية
Combining evidence from Mendelian randomization and colocalization: Review and comparison of approaches.
| العنوان: | Combining evidence from Mendelian randomization and colocalization: Review and comparison of approaches. |
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| المؤلفون: | Zuber V; Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, UK; MRC Centre for Environment and Health, School of Public Health, Imperial College London, London, UK; UK Dementia Research Institute at Imperial College, Imperial College London, London, UK., Grinberg NF; National Institute of Agricultural Botany, Cambridge, UK., Gill D; Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, UK; Clinical Pharmacology and Therapeutics Section, Institute of Medical and Biomedical Education and Institute for Infection and Immunity, St George's, University of London, London, UK; Clinical Pharmacology Group, Pharmacy and Medicines Directorate, St George's University Hospitals NHS Foundation Trust, London, UK; Genetics Department, Novo Nordisk Research Centre Oxford, Oxford, UK., Manipur I; Cambridge Institute of Therapeutic Immunology & Infectious Disease, University of Cambridge, Cambridge, UK; Department of Medicine, School of Clinical Medicine, University of Cambridge, Cambridge, UK., Slob EAW; MRC Biostatistics Unit, University of Cambridge, Cambridge, UK., Patel A; MRC Biostatistics Unit, University of Cambridge, Cambridge, UK., Wallace C; Cambridge Institute of Therapeutic Immunology & Infectious Disease, University of Cambridge, Cambridge, UK; Department of Medicine, School of Clinical Medicine, University of Cambridge, Cambridge, UK; MRC Biostatistics Unit, University of Cambridge, Cambridge, UK., Burgess S; MRC Biostatistics Unit, University of Cambridge, Cambridge, UK; Cardiovascular Epidemiology Unit, Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK. Electronic address: sb452@medschl.cam.ac.uk. |
| المصدر: | American journal of human genetics [Am J Hum Genet] 2022 May 05; Vol. 109 (5), pp. 767-782. Date of Electronic Publication: 2022 Apr 21. |
| نوع المنشور: | Journal Article; Review; Research Support, Non-U.S. Gov't |
| اللغة: | English |
| بيانات الدورية: | Publisher: Cell Press Country of Publication: United States NLM ID: 0370475 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1537-6605 (Electronic) Linking ISSN: 00029297 NLM ISO Abbreviation: Am J Hum Genet Subsets: MEDLINE |
| أسماء مطبوعة: | Publication: 2008- : [Cambridge, MA] : Cell Press Original Publication: Baltimore, American Society of Human Genetics. |
| مواضيع طبية MeSH: | Genome-Wide Association Study* , Mendelian Randomization Analysis*, Causality ; Humans ; Phenotype |
| مستخلص: | Mendelian randomization and colocalization are two statistical approaches that can be applied to summarized data from genome-wide association studies (GWASs) to understand relationships between traits and diseases. However, despite similarities in scope, they are different in their objectives, implementation, and interpretation, in part because they were developed to serve different scientific communities. Mendelian randomization assesses whether genetic predictors of an exposure are associated with the outcome and interprets an association as evidence that the exposure has a causal effect on the outcome, whereas colocalization assesses whether two traits are affected by the same or distinct causal variants. When considering genetic variants in a single genetic region, both approaches can be performed. While a positive colocalization finding typically implies a non-zero Mendelian randomization estimate, the reverse is not generally true: there are several scenarios which would lead to a non-zero Mendelian randomization estimate but lack evidence for colocalization. These include the existence of distinct but correlated causal variants for the exposure and outcome, which would violate the Mendelian randomization assumptions, and a lack of strong associations with the outcome. As colocalization was developed in the GWAS tradition, typically evidence for colocalization is concluded only when there is strong evidence for associations with both traits. In contrast, a non-zero estimate from Mendelian randomization can be obtained despite only nominally significant genetic associations with the outcome at the locus. In this review, we discuss how the two approaches can provide complementary information on potential therapeutic targets. Competing Interests: Declaration of interests D.G. is a part-time employee of Novo Nordisk. I.M. and C.W. are wholly or partially funded by a grant from GSK and MSD. The other authors have no relevant conflict of interest to declare. (Copyright © 2022 American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.) |
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| معلومات مُعتمدة: | MC_PC_17228 United Kingdom MRC_ Medical Research Council; 220788 United Kingdom WT_ Wellcome Trust; 204623 United Kingdom WT_ Wellcome Trust; MC_UU_00002/7 United Kingdom MRC_ Medical Research Council; MR/W029790/1 United Kingdom MRC_ Medical Research Council; MR/S019669/1 United Kingdom MRC_ Medical Research Council; MC_QA137853 United Kingdom MRC_ Medical Research Council; United Kingdom WT_ Wellcome Trust; MC_UU_00002/4 United Kingdom MRC_ Medical Research Council |
| فهرسة مساهمة: | Keywords: Causal inference; Genetic epidemiology; phenome-wide association study; post-GWAS investigations; shared heritability |
| تواريخ الأحداث: | Date Created: 20220422 Date Completed: 20220510 Latest Revision: 20240313 |
| رمز التحديث: | 20240313 |
| مُعرف محوري في PubMed: | PMC7612737 |
| DOI: | 10.1016/j.ajhg.2022.04.001 |
| PMID: | 35452592 |
| قاعدة البيانات: | MEDLINE |
| تدمد: | 1537-6605 |
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| DOI: | 10.1016/j.ajhg.2022.04.001 |