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Mendelian randomization studies of biomarkers and type 2 diabetes.


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Authors

Abbasi, Ali 

Abstract

Many biomarkers are associated with type 2 diabetes (T2D) risk in epidemiological observations. The aim of this study was to identify and summarize current evidence for causal effects of biomarkers on T2D. A systematic literature search in PubMed and EMBASE (until April 2015) was done to identify Mendelian randomization studies that examined potential causal effects of biomarkers on T2D. To replicate the findings of identified studies, data from two large-scale, genome-wide association studies (GWAS) were used: DIAbetes Genetics Replication And Meta-analysis (DIAGRAMv3) for T2D and the Meta-Analyses of Glucose and Insulin-related traits Consortium (MAGIC) for glycaemic traits. GWAS summary statistics were extracted for the same genetic variants (or proxy variants), which were used in the original Mendelian randomization studies. Of the 21 biomarkers (from 28 studies), ten have been reported to be causally associated with T2D in Mendelian randomization. Most biomarkers were investigated in a single cohort study or population. Of the ten biomarkers that were identified, nominally significant associations with T2D or glycaemic traits were reached for those genetic variants related to bilirubin, pro-B-type natriuretic peptide, delta-6 desaturase and dimethylglycine based on the summary data from DIAGRAMv3 or MAGIC. Several Mendelian randomization studies investigated the nature of associations of biomarkers with T2D. However, there were only a few biomarkers that may have causal effects on T2D. Further research is needed to broadly evaluate the causal effects of multiple biomarkers on T2D and glycaemic traits using data from large-scale cohorts or GWAS including many different genetic variants.

Description

This is the author accepted manuscript. The final version is available from Bioscientifica via http://dx.doi.org/10.1530/EC-15-0087

Keywords

Mendelian randomization, biomarkers, epidemiology, genome-wide association study, type 2 diabetes

Journal Title

Endocr Connect

Conference Name

Journal ISSN

2049-3614
2049-3614

Volume Title

4

Publisher

Bioscientifica
Sponsorship
Medical Research Council (MC_UU_12015/1)
This work was supported by the Netherlands Organization for Scientific Research project (NWO), and the Medical Research Council UK (grant no. MC_UU_12015/1). AA is supported by a Rubicon grant from the NWO (Project no. 825.13.004).