Association of BDNF with restricting anorexia nervosa and minimum body mass index: a family-based association study of eight European populations.
Eating disorders (ED), such as anorexia nervosa (AN) and bulimia nervosa (BN), are complex psychiatric disorders where different genetic and environmental factors are involved. Several lines of evidence support that brain-derived neurotrophic factor (BDNF) plays an essential role in eating behaviour and that alterations on this neurotrophic system participates in the susceptibility to both AN and BN. Accordingly, intraventricular administration of BDNF in rats determines food starvation and body weight loss, while BDNF or its specific receptor NTRK2 knockout mice develop obesity and hyperphagia. Case-control studies also suggest a BDNF contribution in the aetiology of ED: we have previously reported a strong association between the Met66 variant within the BDNF gene, restricting AN (ANR) and minimum body mass index (minBMI) in a Spanish sample, and a positive association between the Val66Met and -270C/T BDNF SNPs and ED in six different European populations. To replicate these results, avoiding population stratification effects, we recruited 453 ED trios from eight European centres and performed a family-based association study. Both haplotype relative risk (HRR) and haplotype-based haplotype relative risk (HHRR) methods showed a positive association between the Met66 allele and ANR. Consistently, we also observed an effect of the Met66 variant on low minBMI and a preferential transmission of the -270C/Met66 haplotype to the affected ANR offspring. These results support the involvement of BDNF in eating behaviour and further suggest its participation in the genetic susceptibility to ED, mainly ANR and low minBMI.
Ribasés
Marta
M
Genes and Disease Program, Center for Genomic Regulation, Barcelona Biomedical Research Park, Barcelona, Spain.
Gratacòs
Mònica
M
Fernández-Aranda
Fernando
F
Bellodi
Laura
L
Boni
Claudette
C
Anderluh
Marija
M
Cristina Cavallini
Maria
M
Cellini
Elena
E
Di Bella
Daniela
D
Erzegovesi
Stefano
S
Foulon
Christine
C
Gabrovsek
Mojca
M
Gorwood
Philip
P
Hebebrand
Johannes
J
Hinney
Anke
A
Holliday
Jo
J
Hu
Xun
X
Karwautz
Andreas
A
Kipman
Amélie
A
Komel
Radovan
R
Nacmias
Benedetta
B
Remschmidt
Helmut
H
Ricca
Valdo
V
Sorbi
Sandro
S
Tomori
Martina
M
Wagner
Gudrun
G
Treasure
Janet
J
Collier
David A
DA
Estivill
Xavier
X
D000328:Adult; D000483:Alleles; D000856:Anorexia Nervosa / Q000453:epidemiology / Q000235:genetics*; D015992:Body Mass Index; D019208:Brain-Derived Neurotrophic Factor / Q000235:genetics*; D002032:Bulimia / Q000453:epidemiology / Q000235:genetics*; D005060:Europe / Q000453:epidemiology; D005190:Family; D005260:Female; D008040:Genetic Linkage; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006239:Haplotypes / Q000235:genetics*; D006801:Humans; D008297:Male
D019208:Brain-Derived Neurotrophic Factor