RT Journal Article
T1 Genetic Association of Major Depression With Atypical Features and Obesity-Related Immunometabolic Dysregulations.
A1 Milaneschi, Yuri
A1 Lamers, Femke
A1 Peyrot, Wouter J
A1 Baune, Bernhard T
A1 Breen, Gerome
A1 Dehghan, Abbas
A1 Forstner, Andreas J
A1 Grabe, Hans J
A1 Homuth, Georg
A1 Kan, Carol
A1 Lewis, Cathryn
A1 Mullins, Niamh
A1 Nauck, Matthias
A1 Pistis, Giorgio
A1 Preisig, Martin
A1 Rivera, Margarita
A1 Rietschel, Marcella
A1 Streit, Fabian
A1 Strohmaier, Jana
A1 Teumer, Alexander
A1 Van der Auwera, Sandra
A1 Wray, Naomi R
A1 Boomsma, Dorret I
A1 Penninx, Brenda W J H
A1 CHARGE Inflammation Working Group and the Major Depressive Disorder Working Group of the Psychiatric Genomics Consortium, 
AB 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.
YR 2017
FD 2017
LK http://hdl.handle.net/10668/11701
UL http://hdl.handle.net/10668/11701
LA en
DS RISalud
RD Apr 4, 2025