دورية أكاديمية
Robust use of phenotypic heterogeneity at drug target genes for mechanistic insights: Application of cis-multivariable Mendelian randomization to GLP1R gene region. ...
| العنوان: | Robust use of phenotypic heterogeneity at drug target genes for mechanistic insights: Application of cis-multivariable Mendelian randomization to GLP1R gene region. ... |
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| المؤلفون: | Patel, Ashish, Gill, Dipender, Shungin, Dmitry, Mantzoros, Christos S, Knudsen, Lotte Bjerre, Bowden, Jack, Burgess, Stephen |
| بيانات النشر: | Wiley |
| سنة النشر: | 2024 |
| المجموعة: | DataCite Metadata Store (German National Library of Science and Technology) |
| مصطلحات موضوعية: | GLP1R agonists, drug target Mendelian randomization, overdispersion heterogeneity, phenotypic heterogeneity, Humans, Mendelian Randomization Analysis, Glucagon-Like Peptide-1 Receptor, Diabetes Mellitus, Type 2, Coronary Artery Disease, Phenotype, Body Mass Index, Polymorphism, Single Nucleotide, Genetic Predisposition to Disease |
| الوصف: | Phenotypic heterogeneity at genomic loci encoding drug targets can be exploited by multivariable Mendelian randomization to provide insight into the pathways by which pharmacological interventions may affect disease risk. However, statistical inference in such investigations may be poor if overdispersion heterogeneity in measured genetic associations is unaccounted for. In this work, we first develop conditional F statistics for dimension-reduced genetic associations that enable more accurate measurement of phenotypic heterogeneity. We then develop a novel extension for two-sample multivariable Mendelian randomization that accounts for overdispersion heterogeneity in dimension-reduced genetic associations. Our empirical focus is to use genetic variants in the GLP1R gene region to understand the mechanism by which GLP1R agonism affects coronary artery disease (CAD) risk. Colocalization analyses indicate that distinct variants in the GLP1R gene region are associated with body mass index and type 2 diabetes ... |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| DOI: | 10.17863/cam.106128 |
| الإتاحة: | https://doi.org/10.17863/cam.106128Test https://www.repository.cam.ac.uk/handle/1810/364436Test |
| حقوق: | open.access ; Creative Commons Attribution 4.0 International ; https://creativecommons.org/licenses/by/4.0/legalcodeTest ; cc-by-4.0 ; http://purl.org/coar/access_right/c_abf2Test |
| رقم الانضمام: | edsbas.E00348BB |
| قاعدة البيانات: | BASE |
| DOI: | 10.17863/cam.106128 |
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