Imperial College London
Professor Philippe Froguel

ProfessorPhilippeFroguel

Faculty of Medicine, Department of Metabolism, Digestion and Reproduction

Chair in Genomic Medicine
 
 
 
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Contact

 

+44 (0)20 7594 6520p.froguel

 
 
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Assistant

 

Mrs Patricia Murphy +44 (0)20 7594 1603

 
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Location

 

E306Burlington DanesHammersmith Campus

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Summary

 

Publications

Citation

BibTex format

@article{Maina:2023:10.2337/dc22-2373,
author = {Maina, JG and Balkhiyarova, Z and Nouwen, A and Pupko, I and Ulrich, A and Boissel, M and Bonnefond, A and Froguel, P and Khamis, A and Prokopenko, I and Kaakinen, M},
doi = {10.2337/dc22-2373},
journal = {Diabetes Care},
pages = {1707--1714},
title = {Bidirectional Mendelian Randomization and Multiphenotype GWAS Show Causality and Shared Pathophysiology Between Depression and Type 2 Diabetes.},
url = {http://dx.doi.org/10.2337/dc22-2373},
volume = {46},
year = {2023}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - OBJECTIVE: Depression is a common comorbidity of type 2 diabetes. We assessed the causal relationships and shared genetics between them. RESEARCH DESIGN AND METHODS: We applied two-sample, bidirectional Mendelian randomization (MR) to assess causality between type 2 diabetes and depression. We investigated potential mediation using two-step MR. To identify shared genetics, we performed 1) genome-wide association studies (GWAS) separately and 2) multiphenotype GWAS (MP-GWAS) of type 2 diabetes (19,344 case subjects, 463,641 control subjects) and depression using major depressive disorder (MDD) (5,262 case subjects, 86,275 control subjects) and self-reported depressive symptoms (n = 153,079) in the UK Biobank. We analyzed expression quantitative trait locus (eQTL) data from public databases to identify target genes in relevant tissues. RESULTS: MR demonstrated a significant causal effect of depression on type 2 diabetes (odds ratio 1.26 [95% CI 1.11-1.44], P = 5.46 × 10-4) but not in the reverse direction. Mediation analysis indicated that 36.5% (12.4-57.6%, P = 0.0499) of the effect from depression on type 2 diabetes was mediated by BMI. GWAS of type 2 diabetes and depressive symptoms did not identify shared loci. MP-GWAS identified seven shared loci mapped to TCF7L2, CDKAL1, IGF2BP2, SPRY2, CCND2-AS1, IRS1, CDKN2B-AS1. MDD has not brought any significant association in either GWAS or MP-GWAS. Most MP-GWAS loci had an eQTL, including single nucleotide polymorphisms implicating the cell cycle gene CCND2 in pancreatic islets and brain and the insulin signaling gene IRS1 in adipose tissue, suggesting a multitissue and pleiotropic underlying mechanism. CONCLUSIONS: Our results highlight the importance to prevent type 2 diabetes at the onset of depressive symptoms and the need to maintain a healthy weight in the context of its effect on depression and type 2 diabetes comorbidity.
AU  - Maina,JG
AU  - Balkhiyarova,Z
AU  - Nouwen,A
AU  - Pupko,I
AU  - Ulrich,A
AU  - Boissel,M
AU  - Bonnefond,A
AU  - Froguel,P
AU  - Khamis,A
AU  - Prokopenko,I
AU  - Kaakinen,M
DO  - 10.2337/dc22-2373
EP  - 1714
PY  - 2023///
SP  - 1707
TI  - Bidirectional Mendelian Randomization and Multiphenotype GWAS Show Causality and Shared Pathophysiology Between Depression and Type 2 Diabetes.
T2  - Diabetes Care
UR  - http://dx.doi.org/10.2337/dc22-2373
UR  - https://www.ncbi.nlm.nih.gov/pubmed/37494602
VL  - 46
ER  -
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