Role of the neurotrophin network in eating disorders' subphenotypes: body mass index and age at onset of the disease.
Eating disorders (ED) are severe psychiatric diseases that most likely result from, and are sustained by socio-cultural, psychological and biological factors. We explored whether members of the neurotrophin family are disease-modifying factors of quantitative traits, potentially contributing to the outcome or prognosis of the disease. We studied lifetime minimum and maximum body mass index (minBMI and maxBMI) and age at onset of the disease in a sample of 991 ED patients from France, Germany, Italy and Spain and analysed 183 genetic variants located in 10 candidate genes encoding different neurotrophins and their receptors. We used a hierarchical model approach to include prior genetic knowledge of the specific and found that variants in CNTF, in its receptor CNTFR, and in NTRK2 were significantly associated with a lower age at onset of the ED. In addition, one variant in NTRK1 was associated with a higher minBMI. The results suggest that for these two subphenotypes, CNTF, CNTFR, NTRK1 and NTRK2 might act as disease-modifying factors and add preliminary evidence to the global hypothesis that EDs are the result of complex interactions and reciprocal controls between the immune, endocrine and central nervous systems.
Gratacòs
Mònica
M
CIBER en Epidemiología y Salud Pública (CIBERESP), Genes and Disease Program, Center for Genomic Regulation (CRG-UPF), Barcelona, Catalonia, Spain.
Escaramís
Geòrgia
G
Bustamante
Mariona
M
Saus
Ester
E
Agüera
Zaida
Z
Bayés
Mònica
M
Cellini
Elena
E
de Cid
Rafael
R
Fernández-Aranda
Fernando
F
Forcano
Laura
L
González
Juan R
JR
Gorwood
Philip
P
Hebebrand
Johannes
J
Hinney
Anke
A
Mercader
Josep M
JM
Nacmias
Benedetta
B
Ramoz
Nicolas
N
Ribasés
Marta
M
Ricca
Valdo
V
Romo
Lucia
L
Sorbi
Sandro
S
Versini
Audrey
A
Estivill
Xavier
X
D000293:Adolescent; D000328:Adult; D017668:Age of Onset; D015992:Body Mass Index; D001835:Body Weight; D020934:Ciliary Neurotrophic Factor / Q000235:genetics*; D001068:Feeding and Eating Disorders / Q000453:epidemiology* / Q000235:genetics* / Q000503:physiopathology; D005260:Female; D005602:France / Q000453:epidemiology; D020022:Genetic Predisposition to Disease; D005858:Germany / Q000453:epidemiology; D006801:Humans; D007558:Italy / Q000453:epidemiology; D008297:Male; D015233:Models, Statistical; D009414:Nerve Growth Factors / Q000235:genetics; D020641:Polymorphism, Single Nucleotide; D020801:Receptor, Ciliary Neurotrophic Factor / Q000235:genetics*; D020917:Receptor, trkA / Q000235:genetics*; D020813:Receptor, trkB / Q000235:genetics*; D012307:Risk Factors; D013030:Spain / Q000453:epidemiology; D055815:Young Adult
D020934:Ciliary Neurotrophic Factor; D009414:Nerve Growth Factors; D020801:Receptor, Ciliary Neurotrophic Factor; D020917:Receptor, trkA; D020813:Receptor, trkB