Department of Public Health and Institute of Epidemiology, College of Public Health, National Taiwan University, Taiwan.
J Psychiatr Res. 2010 Jul;44(9):616-9. doi: 10.1016/j.jpsychires.2009.12.005. Epub 2010 Jan 13.
Major depression is more prevalent among individuals with alcoholism than in the general population. Twin studies have found a moderate degree of genetic correlation for alcohol dependence (AD) and major depression (MD), suggesting the existence of loci that confer susceptibility to both disorders. The aim of the present study was to conduct genome-wide linkage analyses to identify loci and to replicate prior evidence for linkage to MD, and to search for linkage regions that may confer risk to the co-occurrence of depression and alcoholism in a sample of sib-pairs affected with AD. A set of 1020 microsatellite markers (average marker spacing of 4cM) were genotyped in 1289 subjects, which consisted of 473 informative families for analysis of depressive traits and 626 sibling pairs for analysis of symptoms of MD and AD. For univariate linkage results for depression, there were six regions (1q, 2p, 4q, 12q, 13q, and 22q) with multipoint LOD scores in excess of 1.00; the highest peak was on chromosome 4q32.3 near marker D4S2952 (LOD=2.17, p=0.0008) for symptoms of MD. Bivariate linkage analysis of symptoms of MD and AD identified only one region at 22q11.21 with LOD>1, which overlapped with the region for symptoms of MD. Several of these regions replicate previously reported linkage results for major depression and emotion-related traits and events, such as neuroticism and suicide attempts. These identified genomic locations, together with results from prior studies, indicate potential regions of interests that may contain susceptibility loci to the risk of depression among individuals with alcohol dependence.
重度抑郁症在酗酒者中的发病率高于普通人群。双胞胎研究发现，酒精依赖（AD）和重度抑郁症（MD）之间存在中度遗传相关性，这表明存在易患两种疾病的基因座。本研究旨在进行全基因组连锁分析，以确定与 MD 相关的基因座，并复制先前与 MD 相关的连锁证据，并在受 AD 影响的同胞对样本中寻找可能导致抑郁和酗酒共病风险的连锁区域。一组 1020 个微卫星标记（平均标记间距为 4cM）在 1289 名受试者中进行了基因分型，其中包括 473 个具有分析抑郁特征的信息性家族和 626 个同胞对，用于分析 MD 和 AD 的症状。对于抑郁的单变量连锁结果，有六个区域（1q、2p、4q、12q、13q 和 22q）多点 LOD 评分超过 1.00；最高峰值位于 4q32.3 附近的标记 D4S2952 处（LOD=2.17，p=0.0008），用于 MD 症状。MD 和 AD 症状的双变量连锁分析仅在 22q11.21 上确定了一个 LOD>1 的区域，该区域与 MD 症状区域重叠。这些区域中的几个复制了先前报道的与重度抑郁症和与情绪相关的特征和事件（如神经质和自杀企图）的连锁结果。这些确定的基因组位置，加上先前研究的结果，表明可能存在与酒精依赖个体抑郁风险相关的易感基因座的潜在感兴趣区域。
