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

Toni-Kim Clarke; Jana Obsteter; Lynsey S Hall; Caroline Hayward; Pippa A Thomson; Blair H Smith; Sandosh Padmanabhan; Lynne J Hocking; Ian J Deary; David J Porteous; Andrew M McIntosh

doi:10.1002/ajmg.b.32478

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

Toni-Kim Clarke, Jana Obsteter, Lynsey S Hall, Caroline Hayward, Pippa A Thomson, Blair H Smith, Sandosh Padmanabhan, Lynne J Hocking, Ian J Deary, David J Porteous, Andrew M McIntosh

School of Medicine, Medical Sciences & Nutrition

Research output: Contribution to journal › Article › peer-review

23 Citations (Scopus)

5 Downloads (Pure)

Abstract

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.

Original language	English
Pages (from-to)	227-234
Number of pages	8
Journal	American Journal of Medical Genetics. Part B, Neuropsychiatric Genetics
Volume	174
Issue number	3
Early online date	2 Aug 2016
DOIs	https://doi.org/10.1002/ajmg.b.32478
Publication status	Published - Apr 2017

Bibliographical note

ACKNOWLEDGEMENTS

We are grateful to the families who took part in GS:SFHS, the GPs and Scottish School of Primary Care for their help in recruiting them, and the whole GS team, which includes academic researchers, clinic staff, laboratory technicians, clerical workers, IT staff, statisticians and research managers. This work is supported by the Wellcome Trust through a Strategic Award, reference 104036/Z/14/Z. The Chief Scientist Office of the Scottish Government and the Scottish Funding Council provided core support for Generation Scotland. GS:SFHS was funded by a grant from the Scottish Government Health Department, Chief Scientist Office, number CZD/16/6. We acknowledge with gratitude the financial support received for this work from the Dr Mortimer and Theresa Sackler Foundation. PT, DJP, IJD, and AMM are members of The University of Edinburgh Centre for Cognitive Ageing and Cognitive Epidemiology, part of the cross council Lifelong Health and Wellbeing Initiative (MR/K026992/1). Funding from the Biotechnology and Biological Sciences Research Council and Medical Research Council is gratefully acknowledged.

Keywords

depression
type 2 diabetes
genetics
polygenic

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

Access to Document

10.1002/ajmg.b.32478Licence: CC BY

Investigating Shared Aetiology Between Type 2 Diabetes and Major Depressive Disorder in a Population Based Cohort
© 2016 The Authors. American Journal of Medical Genetics Part B: Neuropsychiatric Genetics Published by Wiley Periodicals, Inc. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. https://creativecommons.org/licenses/by/4.0/
Final published version, 106 KBLicence: CC BY

Cite this

Clarke, T.-K., Obsteter, J., Hall, L. S., Hayward, C., Thomson, P. A., Smith, B. H., Padmanabhan, S., Hocking, L. J., Deary, I. J., Porteous, D. J., & McIntosh, A. M. (2017). Investigating shared aetiology between type 2 diabetes and major depressive disorder in a population based cohort. American Journal of Medical Genetics. Part B, Neuropsychiatric Genetics, 174(3), 227-234. https://doi.org/10.1002/ajmg.b.32478

Clarke, T-K, Obsteter, J, Hall, LS, Hayward, C, Thomson, PA, Smith, BH, Padmanabhan, S, Hocking, LJ, Deary, IJ, Porteous, DJ & McIntosh, AM 2017, 'Investigating shared aetiology between type 2 diabetes and major depressive disorder in a population based cohort', American Journal of Medical Genetics. Part B, Neuropsychiatric Genetics, vol. 174, no. 3, pp. 227-234. https://doi.org/10.1002/ajmg.b.32478

@article{b7ce4c05486f435aa626724d809459e6,

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

abstract = "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. {\textcopyright} 2016 The Authors. American Journal of Medical Genetics Part B: Neuropsychiatric Genetics Published by Wiley Periodicals, Inc.",

keywords = "depression, type 2 diabetes, genetics, polygenic",

author = "Toni-Kim Clarke and Jana Obsteter and Hall, {Lynsey S} and Caroline Hayward and Thomson, {Pippa A} and Smith, {Blair H} and Sandosh Padmanabhan and Hocking, {Lynne J} and Deary, {Ian J} and Porteous, {David J} and McIntosh, {Andrew M}",

note = "ACKNOWLEDGEMENTS We are grateful to the families who took part in GS:SFHS, the GPs and Scottish School of Primary Care for their help in recruiting them, and the whole GS team, which includes academic researchers, clinic staff, laboratory technicians, clerical workers, IT staff, statisticians and research managers. This work is supported by the Wellcome Trust through a Strategic Award, reference 104036/Z/14/Z. The Chief Scientist Office of the Scottish Government and the Scottish Funding Council provided core support for Generation Scotland. GS:SFHS was funded by a grant from the Scottish Government Health Department, Chief Scientist Office, number CZD/16/6. We acknowledge with gratitude the financial support received for this work from the Dr Mortimer and Theresa Sackler Foundation. PT, DJP, IJD, and AMM are members of The University of Edinburgh Centre for Cognitive Ageing and Cognitive Epidemiology, part of the cross council Lifelong Health and Wellbeing Initiative (MR/K026992/1). Funding from the Biotechnology and Biological Sciences Research Council and Medical Research Council is gratefully acknowledged.",

year = "2017",

month = apr,

doi = "10.1002/ajmg.b.32478",

language = "English",

volume = "174",

pages = "227--234",

journal = "American Journal of Medical Genetics. Part B, Neuropsychiatric Genetics",

issn = "1552-4841",

publisher = "Wiley",

number = "3",

}

TY - JOUR

T1 - Investigating shared aetiology between type 2 diabetes and major depressive disorder in a population based cohort

AU - Clarke, Toni-Kim

AU - Obsteter, Jana

AU - Hall, Lynsey S

AU - Hayward, Caroline

AU - Thomson, Pippa A

AU - Smith, Blair H

AU - Padmanabhan, Sandosh

AU - Hocking, Lynne J

AU - Deary, Ian J

AU - Porteous, David J

AU - McIntosh, Andrew M

N1 - ACKNOWLEDGEMENTS We are grateful to the families who took part in GS:SFHS, the GPs and Scottish School of Primary Care for their help in recruiting them, and the whole GS team, which includes academic researchers, clinic staff, laboratory technicians, clerical workers, IT staff, statisticians and research managers. This work is supported by the Wellcome Trust through a Strategic Award, reference 104036/Z/14/Z. The Chief Scientist Office of the Scottish Government and the Scottish Funding Council provided core support for Generation Scotland. GS:SFHS was funded by a grant from the Scottish Government Health Department, Chief Scientist Office, number CZD/16/6. We acknowledge with gratitude the financial support received for this work from the Dr Mortimer and Theresa Sackler Foundation. PT, DJP, IJD, and AMM are members of The University of Edinburgh Centre for Cognitive Ageing and Cognitive Epidemiology, part of the cross council Lifelong Health and Wellbeing Initiative (MR/K026992/1). Funding from the Biotechnology and Biological Sciences Research Council and Medical Research Council is gratefully acknowledged.

PY - 2017/4

Y1 - 2017/4

N2 - 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.

AB - 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.

KW - depression

KW - type 2 diabetes

KW - genetics

KW - polygenic

U2 - 10.1002/ajmg.b.32478

DO - 10.1002/ajmg.b.32478

M3 - Article

C2 - 27480393

SN - 1552-4841

VL - 174

SP - 227

EP - 234

JO - American Journal of Medical Genetics. Part B, Neuropsychiatric Genetics

JF - American Journal of Medical Genetics. Part B, Neuropsychiatric Genetics

IS - 3

ER -

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

Abstract

Bibliographical note

Keywords

UN SDGs

Access to Document

Fingerprint

Cite this