Middeldorp Christel M, Sullivan Patrick F, Wray Naomi R, Hottenga Jouke-Jan, de Geus Eco J C, van den Berg Mireille, Montgomery Grant W, Coventry Will L, Statham Dixie J, Andrews Gavin, Slagboom P Eline, Boomsma Dorret I, Martin Nicholas G
Department of Biological Psychology, VU University, Amsterdam, The Netherlands.
Am J Med Genet B Neuropsychiatr Genet. 2009 Apr 5;150B(3):352-8. doi: 10.1002/ajmg.b.30817.
It is well established that major depressive disorder (MDD) is partly heritable. We present a genome-wide linkage study aiming to find regions on the genome that influence the vulnerability for MDD. Our sample consists of 110 Australian and 23 Dutch pedigrees with two or more siblings affected with MDD (total N = 278). Linkage analysis was carried out in MERLIN. Three regions showed suggestive linkage signals. The highest LOD-score of 2.1 was found on chromosome 17 at 52.6 cM along with LOD scores of 1.9 and 1.7 on chromosome 8 at 2.7 cM and chromosome 2 at 90.6 cM, respectively. The result on chromosome 8 seems most promising as two previous studies also found linkage in this region, once suggestive and once significant. The linkage peak on chromosome 17 harbors the serotonin transporter gene. In the Australian and Dutch sample, the serotonin transporter length polymorphism did not show evidence for association, thus other genes in this region or other polymorphisms in the serotonin transporter gene might be associated with MDD. Further replication is needed to establish the relevance of our linkage finding on chromosome 2.
重度抑郁症(MDD)具有部分遗传性,这一点已得到充分证实。我们开展了一项全基因组连锁研究,旨在寻找基因组上影响MDD易感性的区域。我们的样本包括110个澳大利亚家系和23个荷兰家系,每个家系中有两个或更多患有MDD的兄弟姐妹(总样本量N = 278)。在MERLIN软件中进行连锁分析。有三个区域显示出提示性连锁信号。在17号染色体上52.6厘摩处发现最高LOD值为2.1,同时在8号染色体上2.7厘摩处和2号染色体上90.6厘摩处的LOD值分别为1.9和1.7。8号染色体上的结果似乎最有前景,因为之前的两项研究也在该区域发现了连锁关系,一次是提示性的,一次是显著的。17号染色体上的连锁峰值区域包含血清素转运体基因。在澳大利亚和荷兰样本中,血清素转运体长度多态性未显示出关联证据,因此该区域的其他基因或血清素转运体基因的其他多态性可能与MDD相关。需要进一步重复研究以确定我们在2号染色体上连锁发现的相关性。