Strauss J, Barr C L, George C J, Devlin B, Vetró A, Kiss E, Baji I, King N, Shaikh S, Lanktree M, Kovacs M, Kennedy J L
Centre for Addiction and Mental Health, University of Toronto, Toronto, ON, Canada.
Mol Psychiatry. 2005 Sep;10(9):861-7. doi: 10.1038/sj.mp.4001685.
Brain-derived neurotrophic factor (BDNF) is a nerve growth factor that has been implicated in the neurobiology of depression. Our group has previously reported an association between a BDNF variant and childhood-onset mood disorder (COMD) in an adult sample from Pittsburgh. We hypothesize that variants at the BDNF locus are associated with COMD. Six BDNF polymorphisms were genotyped in 258 trios having juvenile probands with childhood-onset DSM-IV major depressive or dysthymic disorder. BDNF markers included the (GT)n microsatellite, Val66Met and four other single-nucleotide polymorphisms (SNPs) distributed across the BDNF gene. Family-based association and evolutionary haplotype analysis methods were used. Analysis of linkage disequilibrium (LD) revealed substantial LD among all six polymorphisms. Analyses of the Val66Met polymorphism demonstrated significant overtransmission of the val allele (chi2=7.12, d.f.=1, P=0.0076). Consistent with the pattern of LD, all other SNPs showed significant biased transmission. The (GT)n microsatellite alleles also indicated a trend towards biased transmission (170 bp: Z=2.095, P=0.036). Significant haplotypes involved Val66Met and BDNF2 (P=0.0029). In this Hungarian sample, we found all five BDNF SNPs tested and a haplotype containing the BDNF Val66Met Val allele to be associated with COMD. These results provide evidence that BDNF variants affect liability to juvenile-onset mood disorders, supported by data from two independent samples.
脑源性神经营养因子（BDNF）是一种神经生长因子，与抑郁症的神经生物学有关。我们小组此前曾报道，在匹兹堡的一个成人样本中，BDNF基因变体与儿童期起病的情绪障碍（COMD）之间存在关联。我们假设BDNF基因座上的变体与COMD有关。对258个三联体进行了基因分型，这些三联体中的青少年先证者患有儿童期起病的DSM-IV重度抑郁或心境恶劣障碍。BDNF标记包括（GT）n微卫星、Val66Met以及分布在BDNF基因上的其他四个单核苷酸多态性（SNP）。使用了基于家系的关联分析和进化单倍型分析方法。连锁不平衡（LD）分析显示，所有六个多态性之间存在显著的LD。对Val66Met多态性的分析表明，val等位基因存在显著的过度传递（χ2=7.12，自由度=1，P=0.0076）。与LD模式一致，所有其他SNP均显示出显著的偏向传递。（GT）n微卫星等位基因也显示出偏向传递的趋势（bp：Z=2.095，P=0.036）。显著的单倍型涉及Val66Met和BDNF2（P=0.0029）。在这个匈牙利样本中，我们发现所检测的所有五个BDNF SNP以及一个包含BDNF Val66Met Val等位基因的单倍型与COMD有关。这些结果提供了证据，表明BDNF变体影响青少年起病的情绪障碍易感性，这得到了来自两个独立样本的数据支持。
