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Investigating shared aetiology between type 2 diabetes and major depressive disorder in a population based cohort

Lookup NU author(s): Dr Lynsey Hall

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This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).


Abstract

© 2016 The Authors. American Journal of Medical Genetics Part B: Neuropsychiatric Genetics Published by Wiley Periodicals, Inc. Type II diabetes (T2D) and major depressive disorder (MDD) are often co-morbid. The reasons for this co-morbidity are unclear. Some studies have highlighted the importance of environmental factors and a causal relationship between T2D and MDD has also been postulated. In the present study we set out to investigate the shared aetiology between T2D and MDD using Mendelian randomization in a population based sample, Generation Scotland: the Scottish Family Health Study (N = 21,516). Eleven SNPs found to be associated with T2D were tested for association with MDD and psychological distress (General Health Questionnaire scores). We also assessed causality and genetic overlap between T2D and MDD using polygenic risk scores (PRS) assembled from the largest available GWAS summary statistics to date. No single T2D risk SNP was associated with MDD in the MR analyses and we did not find consistent evidence of genetic overlap between MDD and T2D in the PRS analyses. Linkage disequilibrium score regression analyses supported these findings as no genetic correlation was observed between T2D and MDD (rG = 0.0278 (S.E. 0.11), P-value = 0.79). As suggested by previous studies, T2D and MDD covariance may be better explained by environmental factors. Future studies would benefit from analyses in larger cohorts where stratifying by sex and looking more closely at MDD cases demonstrating metabolic dysregulation is possible. © 2016 The Authors. American Journal of Medical Genetics Part B: Neuropsychiatric Genetics Published by Wiley Periodicals, Inc.


Publication metadata

Author(s): Clarke T-K, Obsteter J, Hall LS, Hayward C, Thomson PA, Smith BH, Padmanabhan S, Hocking LJ, Deary IJ, Porteous DJ, McIntosh AM

Publication type: Article

Publication status: Published

Journal: American Journal of Medical Genetics Part B: Neuropsychiatric Genetics

Year: 2017

Volume: 174

Issue: 3

Pages: 227-234

Print publication date: 01/04/2017

Online publication date: 02/08/2016

Acceptance date: 15/07/2016

Date deposited: 24/04/2017

ISSN (print): 1552-4841

ISSN (electronic): 1552-485X

Publisher: Blackwell Publishing Inc.

URL: https://doi.org/10.1002/ajmg.b.32478

DOI: 10.1002/ajmg.b.32478


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Funding

Funder referenceFunder name
104036/Z/14/Z
CZD/16/6
MR/K026992/1

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