Genetic Association of Major Depression With Atypical Features and Obesity-Related Immunometabolic Dysregulations

Milaneschi, Yuri, Lamers, Femke, Peyrot, Wouter J., Baune, Bernhard T., Breen, Gerome, Dehghan, Abbas, Forstner, Andreas J., Grabe, Hans J., Homuth, Georg, Kan, Carol, Lewis, Cathryn, Mullins, Niamh, Nauck, Matthias, Pistis, Giorgio, Preisig, Martin, Rivera, Margarita, Rietschel, Marcella, Streit, Fabian, Strohmaier, Jana, Teumer, Alexander, Van der Auwera, Sandra, Wray, Naomi R., Boomsma, Dorret I., Penninx, Brenda W. J. H. and for the CHARGE Inflammation Working Group and the Major Depressive Disorder Working Group of the Psychiatric Genomics Consortium (2017) Genetic Association of Major Depression With Atypical Features and Obesity-Related Immunometabolic Dysregulations. JAMA Psychiatry, 74 12: 1214-1225. doi:10.1001/jamapsychiatry.2017.3016


Author Milaneschi, Yuri
Lamers, Femke
Peyrot, Wouter J.
Baune, Bernhard T.
Breen, Gerome
Dehghan, Abbas
Forstner, Andreas J.
Grabe, Hans J.
Homuth, Georg
Kan, Carol
Lewis, Cathryn
Mullins, Niamh
Nauck, Matthias
Pistis, Giorgio
Preisig, Martin
Rivera, Margarita
Rietschel, Marcella
Streit, Fabian
Strohmaier, Jana
Teumer, Alexander
Van der Auwera, Sandra
Wray, Naomi R.
Boomsma, Dorret I.
Penninx, Brenda W. J. H.
for the CHARGE Inflammation Working Group and the Major Depressive Disorder Working Group of the Psychiatric Genomics Consortium
Title Genetic Association of Major Depression With Atypical Features and Obesity-Related Immunometabolic Dysregulations
Journal name JAMA Psychiatry   Check publisher's open access policy
ISSN 2168-6238
2168-622X
Publication date 2017-10-18
Year available 2017
Sub-type Article (original research)
DOI 10.1001/jamapsychiatry.2017.3016
Open Access Status Not yet assessed
Volume 74
Issue 12
Start page 1214
End page 1225
Total pages 12
Place of publication Chicago, IL United States
Publisher American Medical Association
Language eng
Subject 2738 Psychiatry and Mental health
Abstract The association between major depressive disorder (MDD) and obesity may stem from shared immunometabolic mechanisms particularly evident in MDD with atypical features, characterized by increased appetite and/or weight (A/W) during an active episode.

To determine whether subgroups of patients with MDD stratified according to the A/W criterion had a different degree of genetic overlap with obesity-related traits (body mass index [BMI] and levels of C-reactive protein [CRP] and leptin).

This multicenter study assembled genome-wide genotypic and phenotypic measures from 14 data sets of the Psychiatric Genomics Consortium. Data sets were drawn from case-control, cohort, and population-based studies, including 26 628 participants with established psychiatric diagnoses and genome-wide genotype data. Data on BMI were available for 15 237 participants. Data were retrieved and analyzed from September 28, 2015, through May 20, 2017.

Lifetime DSM-IV MDD was diagnosed using structured diagnostic instruments. Patients with MDD were stratified into subgroups according to change in the DSM-IV A/W symptoms as decreased or increased.

Data included 11 837 participants with MDD and 14 791 control individuals, for a total of 26 628 participants (59.1% female and 40.9% male). Among participants with MDD, 5347 (45.2%) were classified in the decreased A/W and 1871 (15.8%) in the increased A/W subgroups. Common genetic variants explained approximately 10% of the heritability in the 2 subgroups. The increased A/W subgroup showed a strong and positive genetic correlation (SE) with BMI (0.53 [0.15]; P = 6.3 × 10-4), whereas the decreased A/W subgroup showed an inverse correlation (-0.28 [0.14]; P = .06). Furthermore, the decreased A/W subgroup had a higher polygenic risk for increased BMI (odds ratio [OR], 1.18; 95% CI, 1.12-1.25; P = 1.6 × 10-10) and levels of CRP (OR, 1.08; 95% CI, 1.02-1.13; P = 7.3 × 10-3) and leptin (OR, 1.09; 95% CI, 1.06-1.12; P = 1.7 × 10-3).

The phenotypic associations between atypical depressive symptoms and obesity-related traits may arise from shared pathophysiologic mechanisms in patients with MDD. Development of treatments effectively targeting immunometabolic dysregulations may benefit patients with depression and obesity, both syndromes with important disability.
Keyword Body-Mass Index
General-Population
Leptin Levels
Fto Gene
Subtypes
Metaanalysis
Symptoms
Disorder
Resistance
Overweight
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: HERDC Pre-Audit
Queensland Brain Institute Publications
Institute for Molecular Bioscience - Publications
 
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Created: Wed, 25 Oct 2017, 21:01:19 EST