Genomewide significant linkage to recurrent, early-onset major depressive disorder on chromosome 15q
Genomewide significant linkage to recurrent, early-onset major depressive disorder on chromosome 15q
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DOI：
10.1086/421333
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发表时间：
2004-06-01
影响因子：
9.8
通讯作者：
Levinson, DF
中科院分区：
文献类型：
--
作者：
Holmans, P;Zubenko, GS;Levinson, DF
对复发性早发性抑郁症遗传学（GenRED）项目的第一阶段样本进行了基因组扫描。样本包括297个信息丰富的家庭，其中包含415对独立的患病兄弟姐妹（asp），或者，计算所有可能的对，685对信息丰富的患病亲属（555对asp和130对其他类型的对）。患者有复发性重度抑郁障碍（MDD），先证患者在31岁前发病，其他患者在41岁前发病；平均发病年龄为18.5岁，平均抑郁发作次数为7.3次。遗传疾病研究中心对389个微卫星标记（平均间距9.3 cM）进行基因分型。主连锁分析利用ALLEGRO程序计算的Z（lr）统计量考虑了所有可能受影响的相对对的等位基因共享。二次逻辑回归分析考虑了配对性别作为协变量的影响。15q25.3-26.2染色体全基因组显著连锁（Z(lr)=4.14，等效LOD=3.73，经验全基因组P= 0.023）。这种联系不是性别特异性的。在初步分析中没有观察到其他提示性或显著的结果。二次分析产生了三个暗示联系的区域，但这些结果应该谨慎解释，因为它们主要依赖于42对雄性-雄性配对的小样本。染色体15q25.3-26.2作为MDD易感性的候选区域值得进一步研究。
A genome scan was performed on the first phase sample of the Genetics of Recurrent Early-Onset Depression (GenRED) project. The sample consisted of 297 informative families containing 415 independent affected sibling pairs (ASPs), or, counting all possible pairs, 685 informative affected relative pairs ( 555 ASPs and 130 other pair types). Affected cases had recurrent major depressive disorder (MDD) with onset before age 31 years for probands or age 41 years for other affected relatives; the mean age at onset was 18.5 years, and the mean number of depressive episodes was 7.3. The Center for Inherited Disease Research genotyped 389 microsatellite markers ( mean spacing of 9.3 cM). The primary linkage analysis considered allele sharing in all possible affected relative pairs with the use of the Z(lr) statistic computed by the ALLEGRO program. A secondary logistic regression analysis considered the effect of the sex of the pair as a covariate. Genomewide significant linkage was observed on chromosome 15q25.3-26.2 (Z(lr)=4.14, equivalent LOD=3.73, empirical genomewide P=.023). The linkage was not sex specific. No other suggestive or significant results were observed in the primary analysis. The secondary analysis produced three regions of suggestive linkage, but these results should be interpreted cautiously because they depended primarily on the small subsample of 42 male-male pairs. Chromosome 15q25.3-26.2 deserves further study as a candidate region for susceptibility to MDD.