Genetic Association of Major Depression With Atypical Features and Obesity-Related Immunometabolic Dysregulations
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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.; CHARGE InflammationWorking Group and the Major Depressive DisorderWorking Group of the Psychiatric Genomics Consortium; Ripke, Stephan; Mattheisen, Manuel; Trzaskowski, Maciej; Byrne, Enda M.; Abdellaoui, Abdel; Adams, Mark J.; Agerbo, Esben; Air, Tracy M.; Andlauer, Till F.M.; Bacanu, Silviu Alin; Bakvad-Hansen, Marie; Beekman, Aartjan T.F.; Bigdeli, Tim B.; Binder, Elisabeth B.; Blackwood, Douglas H.R.; Bryois, Julien; Buttenschon, Henriette N.; Bybjerg-Grauholm, Jonas; Cai, Na; Hansen, Christine Soholm; Hansen, Thomas F.; Krogh, Jesper; Pedersen, Carsten Bocker; Pedersen, Marianne Giortz; Nordentoft, Merete; Werge, Thomas.
I: JAMA Psychiatry, Bind 74, Nr. 12, 12.2017, s. 1214-1225.Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
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TY - JOUR
T1 - Genetic Association of Major Depression With Atypical Features and Obesity-Related Immunometabolic Dysregulations
AU - Milaneschi, Yuri
AU - Lamers, Femke
AU - Peyrot, Wouter J.
AU - Baune, Bernhard T.
AU - Breen, Gerome
AU - Dehghan, Abbas
AU - Forstner, Andreas J.
AU - Grabe, Hans J.
AU - Homuth, Georg
AU - Kan, Carol
AU - Lewis, Cathryn
AU - Mullins, Niamh
AU - Nauck, Matthias
AU - Pistis, Giorgio
AU - Preisig, Martin
AU - Rivera, Margarita
AU - Rietschel, Marcella
AU - Streit, Fabian
AU - Strohmaier, Jana
AU - Teumer, Alexander
AU - Van Der Auwera, Sandra
AU - Wray, Naomi R.
AU - Boomsma, Dorret I.
AU - Penninx, Brenda W.J.H.
AU - CHARGE InflammationWorking Group and the Major Depressive DisorderWorking Group of the Psychiatric Genomics Consortium
AU - Ripke, Stephan
AU - Mattheisen, Manuel
AU - Trzaskowski, Maciej
AU - Byrne, Enda M.
AU - Abdellaoui, Abdel
AU - Adams, Mark J.
AU - Agerbo, Esben
AU - Air, Tracy M.
AU - Andlauer, Till F.M.
AU - Bacanu, Silviu Alin
AU - Bakvad-Hansen, Marie
AU - Beekman, Aartjan T.F.
AU - Bigdeli, Tim B.
AU - Binder, Elisabeth B.
AU - Blackwood, Douglas H.R.
AU - Bryois, Julien
AU - Buttenschon, Henriette N.
AU - Bybjerg-Grauholm, Jonas
AU - Cai, Na
AU - Hansen, Christine Soholm
AU - Hansen, Thomas F.
AU - Krogh, Jesper
AU - Pedersen, Carsten Bocker
AU - Pedersen, Marianne Giortz
AU - Nordentoft, Merete
AU - Werge, Thomas
N1 - Correction: https://jamanetwork.com/journals/jamapsychiatry/fullarticle/2664181
PY - 2017/12
Y1 - 2017/12
N2 - IMPORTANCE The association between major depressive disorder (MDD) and obesitymay 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. OBJECTIVE 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). DESIGN, SETTING, AND PATIENTS 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. MAIN OUTCOMES AND MEASURES Lifetime DSM-IV MDDwas 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. RESULTS 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). CONCLUSIONS AND RELEVANCE 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.
AB - IMPORTANCE The association between major depressive disorder (MDD) and obesitymay 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. OBJECTIVE 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). DESIGN, SETTING, AND PATIENTS 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. MAIN OUTCOMES AND MEASURES Lifetime DSM-IV MDDwas 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. RESULTS 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). CONCLUSIONS AND RELEVANCE 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.
U2 - 10.1001/jamapsychiatry.2017.3016
DO - 10.1001/jamapsychiatry.2017.3016
M3 - Journal article
C2 - 29049554
AN - SCOPUS:85038239250
VL - 74
SP - 1214
EP - 1225
JO - JAMA Psychiatry
JF - JAMA Psychiatry
SN - 2168-622X
IS - 12
ER -
ID: 196736237