TY - JOUR
T1 - Association of BDNF with restricting anorexia nervosa and minimum body mass index
T2 - A family-based association study of eight European populations
AU - Ribasés, Marta
AU - Gratacòs, Mònica
AU - Fernández-Aranda, Fernando
AU - Bellodi, Laura
AU - Boni, Claudette
AU - Anderluh, Marija
AU - Cavallini, Maria Cristina
AU - Cellini, Elena
AU - Di Bella, Daniela
AU - Erzegovesi, Stefano
AU - Foulon, Christine
AU - Gabrovsek, Mojca
AU - Gorwood, Philip
AU - Hebebrand, Johannes
AU - Hinney, Anke
AU - Holliday, Jo
AU - Hu, Xun
AU - Karwautz, Andreas
AU - Kipman, Amélie
AU - Komel, Radovan
AU - Nacmias, Benedetta
AU - Remschmidt, Helmut
AU - Ricca, Valdo
AU - Sorbi, Sandro
AU - Tomori, Martina
AU - Wagner, Gudrun
AU - Treasure, Janet
AU - Collier, David A.
AU - Estivill, Xavier
PY - 2005/4
Y1 - 2005/4
N2 - 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.
AB - 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.
KW - Anorexia
KW - BDNF
KW - Eating disorders
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U2 - 10.1038/sj.ejhg.5201351
DO - 10.1038/sj.ejhg.5201351
M3 - Article
C2 - 15657604
AN - SCOPUS:20244381139
VL - 13
SP - 428
EP - 434
JO - European Journal of Human Genetics
JF - European Journal of Human Genetics
SN - 1018-4813
IS - 4
ER -