Genetics of recurrent early-onset major depression (GenRED): significant linkage on chromosome 15q25-q26 after fine mapping with single nucleotide polymorphism markers.
Genetics of recurrent early-onset major depression (GenRED): significant linkage on chromosome 15q25-q26 after fine mapping with single nucleotide polymorphism markers.
复制标题
复发性早发性重度抑郁症 (GenRED) 的遗传学：使用单核苷酸多态性标记进行精细定位后，染色体 15q25-q26 上存在显着连锁。
DOI：
10.1176/ajp.2007.164.2.259
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发表时间：
2007
期刊：
影响因子：
--
通讯作者：
Mille
中科院分区：
文献类型：
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作者：
Levinson,DouglasF;Evgrafov,OlegV;Knowles,JamesA;Potash,JamesB;Weissman,MyrnaM;Scheftner,WilliamA;DepauloJr,JRaymond;Crowe,RaymondR;Murphy-Eberenz,Kathleen;Marta,DianaH;McInnis,MelvinG;Adams,Philip;Gladis,Madeline;Mille
作者研究了染色体15 q25-q26上的单核苷酸多态性（SNP）DNA标记的密集图，以最大化在他们先前报道的复发性早发性重性抑郁症连锁的暗示证据的区域中的遗传连锁分析的信息量。并进行多点等位基因共享连锁分析。标记-标记连锁不平衡被最小化，并与创始人单倍型从这些家庭的模拟研究表明，连锁分数不膨胀的连锁disequilibrium.ResultsThe密集的SNP地图增加了信息内容的分析从0.7左右，超过0.9。关联的最大证据是Kong和考克斯的Z似然比评分统计量（ZLR）=4.69（109.8 cM）。精确的p值低于全基因组显著性阈值。相比之下，在基因组扫描微卫星标记在9 cM的间距，最大的ZLR为欧洲血统的家庭是3.43（106.53 cM）。据估计，在这一地区的连锁位点或位点可能占20%或更少的人口范围内增加的风险，兄弟姐妹的cases.ConclusionsThis区域产生了适度的积极证据，在其他研究中的抑郁症和相关特征的联系。这些结果表明，15 q25-q26区域中一个或多个基因的DNA序列变异可以增加对重性抑郁症的易感性，并且有必要努力识别这些基因。
ObjectiveThe authors studied a dense map of single nucleotide polymorphism (SNP) DNA markers on chromosome 15q25-q26 to maximize the informativeness of genetic linkage analyses in a region where they previously reported suggestive evidence for linkage of recurrent early-onset major depressive disorder.MethodIn 631 European-ancestry families with multiple cases of recurrent early-onset major depressive disorder, 88 SNPs were genotyped, and multipoint allele-sharing linkage analyses were carried out. Marker-marker linkage disequilibrium was minimized, and a simulation study with founder haplotypes from these families suggested that linkage scores were not inflated by linkage disequilibrium.ResultsThe dense SNP map increased the information content of the analysis from around 0.7 to over 0.9. The maximum evidence for linkage was the Z likelihood ratio score statistic of Kong and Cox (ZLR)=4.69 at 109.8 cM. The exact p value was below the genomewide significance threshold. By contrast, in the genome scan with microsatellite markers at 9 cM spacing, the maximum ZLRfor European-ancestry families was 3.43 (106.53 cM). It was estimated that the linked locus or loci in this region might account for a 20% or less populationwide increase in risk to siblings of cases.ConclusionsThis region has produced modestly positive evidence for linkage to depression and related traits in other studies. These results suggest that DNA sequence variations in one or more genes in the 15q25-q26 region can increase susceptibility to major depression and that efforts are warranted to identify these genes.