Genetics of recurrent early-onset major depression (GenRED): Final genome scan report
Genetics of recurrent early-onset major depression (GenRED): Final genome scan report
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DOI：
10.1176/appi.ajp.164.2.248
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发表时间：
2007-02-01
影响因子：
17.7
通讯作者：
Levinson, Douglas F.
中科院分区：
文献类型：
--
作者：
Holmans, Peter;Weissman, Myrna M.;Levinson, Douglas F.
目的：作者进行了全基因组连锁扫描，以确定可能包含导致复发性早发性重性抑郁症易感性的基因的染色体区域，早发性重性抑郁症是指数病例亲属报告风险最大的疾病形式。方法：对656个有两个或两个以上此类病例（先证31岁前发病，其他亲属41岁发病）的家庭进行微卫星DNA标记研究，包括1494对信息“所有可能”的患病亲属对（894对独立患病兄弟姐妹）。分析包括一次多点等位基因共享分析（使用ALLEGRO）和二次逻辑回归分析，考虑到每对亲属的性别（男-男、男-女、女-女）。结果：在15q25-q26染色体（105.4 cM）上观察到全基因组连锁的提示证据。作者先前报道了前297个家族在该区域的全基因组显著联系。在二次分析中，经过多次检验的全基因组校正，在染色体17p12 （28.0 cM，在雄性和雌性对中共享过多）和染色体8p22-p21.3 （25.1 cM，在雄性和雌性对中共享过多）上观察到提示连锁结果。结论：染色体15q、17p和8p的这些区域可能含有导致重度抑郁症和相关疾病易感性的基因。在染色体15q与重度抑郁症相关的区域和染色体8p与相关的人格特征相关的区域都有独立的关联证据。
Objective: The authors carried out a genomewide linkage scan to identify chromosomal regions likely to contain genes that contribute to susceptibility to recurrent early-onset major depressive disorder, the form of the disorder with the greatest reported risk to relatives of index cases.Method: Microsatellite DNA markers were studied in 656 families with two or more such cases (onset before age 31 in probands and age 41 in other relatives), including 1,494 informative "all possible" affected relative pairs (there were 894 independent affected sibling pairs). Analyses included a primary multipoint allele-sharing analysis (with ALLEGRO) and a secondary logistic regression analysis taking the sex of each relative pair into account (male-male, male-female, female-female).Results: Genomewide suggestive evidence for linkage was observed on chromosome 15q25-q26 (at 105.4 centimorgans [cM]). The authors previously reported genomewide significant linkage in this region in the first 297 families. In the secondary analysis, after empirical genomewide correction for multiple testing, suggestive linkage results were observed on chromosome 17p12 (28.0 cM, excess sharing in male-male and male-female pairs) and on chromosome 8p22-p21.3 (25.1 cM, excess sharing in male-male pairs).Conclusions: These regions of chromosomes 15q, 17p, and 8p might contain genes that contribute to susceptibility to major depression and related disorders. Evidence for linkage has been reported independently in the same regions of chromosome 15q for major depression and of chromosome 8p for related personality traits.