Predisposition locus for major depression at chromosome 12q22-12q23.2
Predisposition locus for major depression at chromosome 12q22-12q23.2
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DOI：
10.1086/379978
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发表时间：
2003-12-01
影响因子：
9.8
通讯作者：
Cannon-Albright, L
中科院分区：
文献类型：
--
作者：
Abkevich, V;Camp, NJ;Cannon-Albright, L
重度抑郁症是一种常见的精神疾病，对社会有重大的经济影响。在许多情况下，没有有效的治疗方法。重性抑郁症的病因很复杂，但很明显，这种疾病在很大程度上是由遗传决定的，特别是在有重性抑郁症家族史的个体中，除了环境因素外，可能还涉及多种易感基因。作为确定导致抑郁症遗传易感性的染色体位点的第一步，我们使用628个微卫星标记对来自110个犹他州家系的1,890名个体进行了全基因组扫描，这些个体具有强烈的抑郁症家族史。我们在标记D12 S1300处确定了与男性重性抑郁症的显著联系（多点异质性LOD评分4.6;经多重检验调整后P = .00003）。使用额外的标记，连锁证据变得非常显著，标记D12 S1706处的多点异质性LOD评分增加到6.1（多重检验调整后P = .0000007）。这项研究证实了在12号染色体q臂上存在一个或多个与精神疾病有关的基因，并为在12 q22-q23.2存在性别特异性抑郁症易感基因提供了强有力的证据。
Major depression disorder is a common psychiatric disease with a major economic impact on society. In many cases, no effective treatment is available. The etiology of major depression is complex, but it is clear that the disease is, to a large extent, determined genetically, especially among individuals with a familial history of major depression, presumably through the involvement of multiple predisposition genes in addition to an environmental component. As a first step toward identification of chromosomal loci contributing to genetic predisposition to major depression, we have conducted a genomewide scan by using 628 microsatellite markers on 1,890 individuals from 110 Utah pedigrees with a strong family history of major depression. We identified significant linkage to major depression in males at marker D12S1300 (multipoint heterogeneity LOD score 4.6; P = .00003 after adjustment for multiple testing). With additional markers, the linkage evidence became highly significant, with the multipoint heterogeneity LOD score at marker D12S1706 increasing to 6.1 (P = .0000007 after adjustment for multiple testing). This study confirms the presence of one or more genes involved in psychiatric diseases on the q arm of chromosome 12 and provides strong evidence for the existence of a sex-specific predisposition gene to major depression at 12q22-q23.2.