Obesity and atypical depression symptoms: Findings from Mendelian randomization in two European cohorts

Giorgio Pistis; Yuri Milaneschi; Caroline L. Vandeleur; Aurélie M. Lasserre; Brenda W.J.H. Penninx; Femke Lamers; Dorret I. Boomsma; Jouke-Jan Hottenga; Pedro Marques-vidal; Peter Vollenweider; Gérard Waeber; Jean-michel Aubry; Martin Preisig; Zoltán Kutalik

doi:10.1038/s41398-021-01236-7

Obesity and atypical depression symptoms: Findings from Mendelian randomization in two European cohorts

Giorgio Pistis
, Yuri Milaneschi
, Caroline L. Vandeleur
, Aurélie M. Lasserre
, Brenda W.J.H. Penninx
, Femke Lamers
, Dorret I. Boomsma
, Jouke-Jan Hottenga
, Pedro Marques-vidal
, Peter Vollenweider
, Gérard Waeber
, Jean-michel Aubry
, Martin Preisig
, Zoltán Kutalik

Research output: Contribution to Journal › Article › Academic › peer-review

Abstract

Studies considering the causal role of body mass index (BMI) for the predisposition of major depressive disorder (MDD) based on a Mendelian Randomization (MR) approach have shown contradictory results. These inconsistent findings may be attributable to the heterogeneity of MDD; in fact, several studies have documented associations between BMI and mainly the atypical subtype of MDD. Using a MR approach, we investigated the potential causal role of obesity in both the atypical subtype and its five specific symptoms assessed according to the Statistical Manual of Mental Disorders (DSM), in two large European cohorts, CoLaus|PsyCoLaus (n = 3350, 1461 cases and 1889 controls) and NESDA|NTR (n = 4139, 1182 cases and 2957 controls). We first tested general obesity measured by BMI and then the body fat distribution measured by waist-to-hip ratio (WHR). Results suggested that BMI is potentially causally related to the symptom increase in appetite, for which inverse variance weighted, simple median and weighted median MR regression estimated slopes were 0.68 (SE = 0.23, p = 0.004), 0.77 (SE = 0.37, p = 0.036), and 1.11 (SE = 0.39, p = 0.004). No causal effect of BMI or WHR was found on the risk of the atypical subtype or for any of the other atypical symptoms. Our findings show that higher obesity is likely causal for the specific symptom of increase in appetite in depressed participants and reiterate the need to study depression at the granular level of its symptoms to further elucidate potential causal relationships and gain additional insight into its biological underpinnings.

Original language	English
Article number	96
Pages (from-to)	1-11
Number of pages	11
Journal	Translational Psychiatry
Volume	11
Early online date	4 Feb 2021
DOIs	https://doi.org/10.1038/s41398-021-01236-7
Publication status	Published - 2021

Funding

The CoLaus PsyCoLaus study was and is supported by research grants from GlaxoSmithKline, the Faculty of Biology and Medicine of Lausanne, and the Swiss National Science Foundation (grants 3200B0-105993, 3200B0-118308, 33CSCO-122661, 33CS30-139468, 33CS30-148401, and 33CS30_177535/1). Yuri Milaneschi is financially partially supported by the Complex Trait Genetics programme of Amsterdam Neuroscience. For NESDA, funding was obtained from the Netherlands Organization for Scientific Research (Geestkracht program grant 10000-1002); the Center for Medical Systems Biology (CSMB, NVVO Genomics), Biobanking and Biomolecular Resources Research Infrastructure (BBMRI-NL), VU University’s Institutes for Health and Care Research (EMGO+) and Neuroscience Campus Amsterdam, University Medical Center Groningen, Leiden University Medical Center, National Institutes of Health (NIH, ROI D0042157-01A, MH081802, Grand Opportunity grants 1 RC2 Ml-1089951 and IRC2 MH089995). Part of the genotyping and analyses were funded by the Genetic Association Information Network (GAIN) of the Foundation for the National Institutes of Health. Computing was supported by BiG Grid, the Dutch e-Science Grid, which is financially supported by NWO. For NTR, funding was obtained from the Netherlands Organization for Scientific Research (NWO) and MagW/ZonMW grants 904-61-090, 985-10-002, 912-10-020, 904-61-193,480-04-004, 463-06-001, 451-04-034, 400-05-717 Addiction-31 160008, Middelgroot-91 1-09-032, Spinozapremie 56-464-14192, Center for Medical Systems Biology (CSMB, NWO Genomics), NBlC/BioAssisURK (2008.024), Biobanking and Biomolecular Resources Research Infrastructure (BBMRI—NL, 184.021.007). VU University’s Institute for Health and Care Research (EMGO+) and Neuroscience Campus Amsterdam (NCA); the European Science Foundation (ESF EU/QLRT-2001-01254), the European Community’s Seventh Framework Program (FP7/2007-2013), ENGAGE (HEALTH-F4-2007-201413); the European Science Council (ERC Advanced, 230374), Rutgers University Cell and DNA Repository (NIMH U24 MH068457-06), the Avera Institute, Sioux Falls, South Dakota (USA), and the National Institutes of Health (NIH, ROI D0042157-01A, MH081802, Grand Opportunity grants IRC2 Ml-1089951 and IRC2 Ml-1089995). Part of the genotyping and analyses were funded by the Genetic Association Information Network (GAIN) of the Foundation for the National Institutes of Health. Computing was supported by BiG Grid, the Dutch e-Science Grid, which is financially supported by NWO.

Funders	Funder number
Centre for Medical Systems Biology
Leids Universitair Medisch Centrum
Université de Lausanne
Biobanking and Biomolecular Resources Research Infrastructure
NBlC
European Science Council
Universitair Medisch Centrum Groningen
Vrije Universiteit Amsterdam
BBMRI-NL
GlaxoSmithKline foundation
BiG Grid
GlaxoSmithKline
VU University’s Institutes for Health and Care Research
Faculty of Biology and Medicine of Lausanne
Chain of Love Foundation
European Research Council	230374
Spinozapremie	56-464-14192
National Institute of Mental Health	R01MH081802, U24MH068457, RC2MH089995
National Institutes of Health	ROI D0042157-01A, 1 RC2 Ml-1089951
BioAssisURK	2008.024
Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung	33CS30-148401, 3200B0-118308, 148401, 105993, 33CS30_177535/1, 33CS30-139468, 33CSCO-122661, 3200B0-105993
European Commission	201413
BBMRI	184.021.007
Seventh Framework Programme	FP7/2007-2013
Avera Institute	IRC2 Ml-1089995, IRC2 Ml-1089951
Nederlandse Organisatie voor Wetenschappelijk Onderzoek	463-06-001, 904-61-090, 904-61-193,480-04-004, 451-04-034, Middelgroot-91 1-09-032, 400-05-717 Addiction-31 160008, 985-10-002, 10000-1002, 912-10-020
European Science Foundation	ESF EU/QLRT-2001-01254
ENGAGE	HEALTH-F4-2007-201413

UN SDGs

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

SDG 3 Good Health and Well-being

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Pistis, G., Milaneschi, Y., Vandeleur, C. L., Lasserre, A. M., Penninx, B. W. J. H., Lamers, F., Boomsma, D. I., Hottenga, J.-J., Marques-vidal, P., Vollenweider, P., Waeber, G., Aubry, J., Preisig, M., & Kutalik, Z. (2021). Obesity and atypical depression symptoms: Findings from Mendelian randomization in two European cohorts. Translational Psychiatry, 11, 1-11. Article 96. https://doi.org/10.1038/s41398-021-01236-7

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abstract = "Studies considering the causal role of body mass index (BMI) for the predisposition of major depressive disorder (MDD) based on a Mendelian Randomization (MR) approach have shown contradictory results. These inconsistent findings may be attributable to the heterogeneity of MDD; in fact, several studies have documented associations between BMI and mainly the atypical subtype of MDD. Using a MR approach, we investigated the potential causal role of obesity in both the atypical subtype and its five specific symptoms assessed according to the Statistical Manual of Mental Disorders (DSM), in two large European cohorts, CoLaus|PsyCoLaus (n = 3350, 1461 cases and 1889 controls) and NESDA|NTR (n = 4139, 1182 cases and 2957 controls). We first tested general obesity measured by BMI and then the body fat distribution measured by waist-to-hip ratio (WHR). Results suggested that BMI is potentially causally related to the symptom increase in appetite, for which inverse variance weighted, simple median and weighted median MR regression estimated slopes were 0.68 (SE = 0.23, p = 0.004), 0.77 (SE = 0.37, p = 0.036), and 1.11 (SE = 0.39, p = 0.004). No causal effect of BMI or WHR was found on the risk of the atypical subtype or for any of the other atypical symptoms. Our findings show that higher obesity is likely causal for the specific symptom of increase in appetite in depressed participants and reiterate the need to study depression at the granular level of its symptoms to further elucidate potential causal relationships and gain additional insight into its biological underpinnings.",

author = "Giorgio Pistis and Yuri Milaneschi and Vandeleur, \{Caroline L.\} and Lasserre, \{Aur{\'e}lie M.\} and Penninx, \{Brenda W.J.H.\} and Femke Lamers and Boomsma, \{Dorret I.\} and Jouke-Jan Hottenga and Pedro Marques-vidal and Peter Vollenweider and G{\'e}rard Waeber and Jean-michel Aubry and Martin Preisig and Zolt{\'a}n Kutalik",

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Pistis, G, Milaneschi, Y, Vandeleur, CL, Lasserre, AM, Penninx, BWJH, Lamers, F, Boomsma, DI, Hottenga, J-J, Marques-vidal, P, Vollenweider, P, Waeber, G, Aubry, J, Preisig, M & Kutalik, Z 2021, 'Obesity and atypical depression symptoms: Findings from Mendelian randomization in two European cohorts', Translational Psychiatry, vol. 11, 96, pp. 1-11. https://doi.org/10.1038/s41398-021-01236-7

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T1 - Obesity and atypical depression symptoms

T2 - Findings from Mendelian randomization in two European cohorts

AU - Pistis, Giorgio

AU - Milaneschi, Yuri

AU - Vandeleur, Caroline L.

AU - Lasserre, Aurélie M.

AU - Penninx, Brenda W.J.H.

AU - Lamers, Femke

AU - Boomsma, Dorret I.

AU - Hottenga, Jouke-Jan

AU - Marques-vidal, Pedro

AU - Vollenweider, Peter

AU - Waeber, Gérard

AU - Aubry, Jean-michel

AU - Preisig, Martin

AU - Kutalik, Zoltán

PY - 2021

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Obesity and atypical depression symptoms: Findings from Mendelian randomization in two European cohorts

Abstract

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