Association of CRTC1 polymorphisms with obesity markers in subjects from the general population with lifetime depression

作者：Quteineh Lina; Preisig Martin; Rivera Margarita; Milaneschi Yuri; Castelao Enrique; Gholam Rezaee Mehdi; Vandenberghe Frederik; Saigi Morgui Nuria; Delacretaz Aurelie; Cardinaux Jean Rene; Willemsen Gonneke; Boomsma Dorret I; Penninx Brenda W J H; Ching Lopez Ana; Conus Philippe; Eap Chin B^*

来源：Journal of Affective Disorders, 2016, 198: 43-49.

DOI：10.1016/j.jad.2016.03.031

• Obesity
• Major depressive disorder
• Psychiatric disorders
• Psychotropic drugs
• Pharmacogenetics
• Genetic polymorphisms

Background: Psychiatric disorders have been hypothesized to share common etiological pathways with obesity, suggesting related neurobiological bases. We aimed to examine whether CRTC1 polymorphisms were associated with major depressive disorder (MDD) and to test the association of these polymorphisms with obesity markers in several large case-control samples with MDD.
Methods: The association between CRTC1 polymorphisms and MDD was investigated in three case control samples with MDD (PsyCoLaus n(1)=3,362, Radiant n(2)=3,148 and NESDA/NTR n(3)=4,663). The effect of CRTC1 polymorphisms on obesity markers was then explored.
Results: CRTC1 polymorphisms were not associated with MDD in the three samples. CRTC1 rs6510997C > T was significantly associated with fat mass in the PsyCoLaus study. In fact, a protective effect of this polymorphism was found in MDD cases (n=1,434, beta=-1.32%, 95% CI -2.07 to -0.57, p < 0.001), but not in controls. In the Radiant study, CRTC1 polymorphisms were associated with BMI, exclusively in individuals with MDD (n=2,138, beta = -0.75 kg/m(2), 95% CI -1.30 to -0.21, p = 0.007), while no association with BMI was found in the NESDA/NTR study.
Limitations: Estimated fat mass using bioimpedance that capture more accurately adiposity was only present in the PsyCoLaus sample.
Conclusions: CRTC1 polymorphisms seem to play a role with obesity markers in individuals with MDD rather than non-depressive individuals. Therefore, the weak association previously reported in the population-based samples was driven by cases diagnosed with lifetime MDD. However, CRTC1 seems not to be implicated directly in the development of psychiatric diseases.

• 出版日期2016-7-1