Influence of CRTC1 polymorphisms on body mass index and fat mass in psychiatric patients and the general adult population.
OBJECTIVE
There is a high prevalence of obesity in psychiatric patients, possibly leading to metabolic complications and reducing life expectancy. The CREB-regulated transcription coactivator 1 (CRTC1) gene is involved in energy balance and obesity in animal models, but its role in human obesity is unknown.


OBJECTIVE
To determine whether polymorphisms within the CRTC1 gene are associated with adiposity markers in psychiatric patients and the general population.


METHODS
Retrospective and prospective data analysis and population-based samples at Lausanne and Geneva university hospitals in Switzerland and a private clinic in Lausanne, Switzerland. The effect of 3 CRTC1 polymorphisms on body mass index (BMI) and/or fat mass was investigated in a discovery cohort of psychiatric outpatients taking weight gain-inducing psychotropic drugs (sample 1, n = 152). The CRTC1 variant that was significantly associated with BMI and survived Bonferroni corrections for multiple comparison was then replicated in 2 independent psychiatric samples (sample 2, n = 174 and sample 3, n = 118) and 2 white population-based samples (sample 4, n = 5338 and sample 5, n = 123,865).


METHODS
Noninterventional studies.


METHODS
Difference in BMI and/or fat mass between CRTC1 genotype groups.


RESULTS
Among the CRTC1 variants tested in the first psychiatric sample, only rs3746266A>G was associated with BMI (P(adjusted) = .003). In the 3 psychiatric samples, carriers of the rs3746266 G allele had a lower BMI than noncarriers (AA genotype) (sample 1, P = .001; sample 2, P = .05; and sample 3, P = .0003). In the combined analysis, excluding patients taking other weight gain-inducing drugs, G allele carriers (n = 98) had a 1.81-kg/m² lower BMI than noncarriers (n = 226; P < .0001). The strongest association was observed in women younger than 45 years, with a 3.87-kg/m² lower BMI in G allele carriers (n = 25) compared with noncarriers (n = 48; P < .0001), explaining 9% of BMI variance. In the population-based samples, the T allele of rs6510997C>T (a proxy of the rs3746266 G allele; r² = 0.7) was associated with lower BMI (sample 5, n = 123,865; P = .01) and fat mass (sample 4, n = 5338; P = .03). The strongest association with fat mass was observed in premenopausal women (n = 1192; P = .02).


CONCLUSIONS
These findings suggest that CRTC1 contributes to the genetics of human obesity in psychiatric patients and the general population. Identification of high-risk subjects could contribute to a better individualization of the pharmacological treatment in psychiatry.
Unit of Pharmacogenetics and Clinical Psychopharmacology, Centre for Psychiatric Neuroscience, Department of Psychiatry, Lausanne University Hospital, Prilly, Switzerland.
Eva
E
Choong
Lina
L
Quteineh
Jean-René
JR
Cardinaux
Mehdi
M
Gholam-Rezaee
Frederik
F
Vandenberghe
Maria
M
Dobrinas
Guido
G
Bondolfi
Manuela
M
Etter
Laurent
L
Holzer
Pierre
P
Magistretti
Armin
A
von Gunten
Martin
M
Preisig
Peter
P
Vollenweider
Jacques S
JS
Beckmann
François P
FP
Pralong
Gerard
G
Waeber
Zoltan
Z
Kutalik
Philippe
P
Conus
Murielle
M
Bochud
Chin B
CB
Eap
D050154:Adiposity / Q000235:genetics*; D000328:Adult; D015992:Body Mass Index; D016022:Case-Control Studies; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D006801:Humans; D008297:Male; D001523:Mental Disorders / Q000150:complications / Q000235:genetics*; D009765:Obesity / Q000150:complications / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D014157:Transcription Factors / Q000235:genetics*
C500984:CRTC1 protein, human; D014157:Transcription Factors