دورية أكاديمية
The contribution of tissue-grouped BMI-associated gene sets to cardiometabolic-disease risk: a Mendelian randomization study
| العنوان: | The contribution of tissue-grouped BMI-associated gene sets to cardiometabolic-disease risk: a Mendelian randomization study |
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| المؤلفون: | Verkouter, I., Mutsert, R. de, Smit, R.A.J., Trompet, S., Rosendaal, F.R., Heemst, D. van, Dijk, K.W. van, Noordam, R. |
| المصدر: | International Journal of Epidemiology |
| سنة النشر: | 2020 |
| المجموعة: | Leiden Repository (Leiden University) |
| مصطلحات موضوعية: | Mendelian randomization analysis, body mass index, type 2 diabetes mellitus, coronary artery disease, waist circumference, anthropometry |
| الوصف: | Background: Body mass index (BMI)-associated loci are used to explore the effects of obesity using Mendelian randomization (MR), but the contribution of individual tissues to risks remains unknown. We aimed to identify tissue-grouped pathways of BMI-associated loci and relate these to cardiometabolic disease using MR analyses.Methods: Using Genotype-Tissue Expression (GTEx) data, we performed overrepresentation tests to identify tissue-grouped gene sets based on mRNA-expression profiles from 634 previously published BMI-associated loci. We conducted two-sample MR with inverse-variance-weighted methods, to examine associations between tissue-grouped BMI-associated genetic instruments and type 2 diabetes mellitus (T2DM) and coronary artery disease (CAD), with use of summary-level data from published genome-wide association studies (T2DM: 74 124 cases, 824 006 controls; CAD: 60 801 cases, 123 504 controls). Additionally, we performed MR analyses on T2DM and CAD using randomly sampled sets of 100 or 200 BMI-associated genetic variants.Results: We identified 17 partly overlapping tissue-grouped gene sets, of which 12 were brain areas, where BMI-associated genes were differentially expressed. In tissue-grouped MR analyses, all gene sets were similarly associated with increased risks of T2DM and CAD. MR analyses with randomly sampled genetic variants on T2DM and CAD resulted in a distribution of effect estimates similar to tissue-grouped gene sets.Conclusions: Overrepresentation tests revealed differential expression of BMI-associated genes in 17 different tissues. However, with our biology-based approach using tissue-grouped MR analyses, we did not identify different risks of T2DM or CAD for the BMI-associated gene sets, which was reflected by similar effect estimates obtained by randomly sampled gene sets. ; Pathophysiology, epidemiology and therapy of ageing |
| نوع الوثيقة: | article in journal/newspaper |
| وصف الملف: | application/pdf |
| اللغة: | English |
| العلاقة: | https://academic.oup.com/ije/article/49/4/1246/5851556Test; lumc-id: 108076054; https://hdl.handle.net/1887/3182380Test |
| DOI: | 10.1093/ije/dyaa070 |
| الإتاحة: | https://doi.org/10.1093/ije/dyaa070Test https://hdl.handle.net/1887/3182380Test https://academic.oup.com/ije/article/49/4/1246/5851556Test |
| رقم الانضمام: | edsbas.4045FBD7 |
| قاعدة البيانات: | BASE |
| DOI: | 10.1093/ije/dyaa070 |
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