Malafosse A, Leboyer M, d'Amato T, Amadéo S, Abbar M, Campion D, Canseil O, Castelnau D, Gheysen F, Granger B, Henrikson B, Poirier M F, Sabaté O, Samolyk D, Feingold J, Mallet J
CNRS UMR 9923, Hôpital Pitié Salpétrière, Paris, France.
Neurobiol Dis. 1997;4(5):337-49. doi: 10.1006/nbdi.1997.0149.
Several studies have implicated the tyrosine hydroxylase (TH) locus within the 11p15 region in susceptibility to manic depressive illness (MDI). This possibility was further investigated by both parametric (lod score) and nonparametric (affected-pedigree-member and a case-control study) methods of analysis in 11 French MDI families and in a sample of 200 unrelated subjects. Both types of analyses corroborate the implication of this locus, and positive lod scores were obtained in two families, which most likely reflects genetic heterogeneity. Statistical analyses were also performed including available data from published reports. These analyses, which allowed for genetic heterogeneity, substantiated our findings. The combined maximum lod score for all the families studied was 3.68 at theta = 0.00 (number of families: 36) assuming heterogeneity (alpha = 15%, P = 0.01). Taken together these results converge to suggest that the risk factors for MDI lie in the 11p15 region with TH being the most likely candidate gene.
多项研究表明，11p15区域内的酪氨酸羟化酶（TH）基因座与躁郁症（MDI）易感性有关。通过参数分析（对数优势分数）和非参数分析（患病家系成员分析及病例对照研究）方法，对11个法国家系及200名无亲缘关系个体样本进行了进一步研究。两种分析方法均证实了该基因座的关联性，在两个家系中获得了阳性对数优势分数，这很可能反映了遗传异质性。还进行了统计分析，纳入了已发表报告中的可用数据。这些考虑到遗传异质性的分析证实了我们的研究结果。假设存在异质性（α = 15%，P = 0.01），所有研究家系的合并最大对数优势分数在θ = 0.00时为3.68（家系数：36）。综合这些结果表明，MDI的风险因素位于11p15区域，其中TH基因最有可能是候选基因。
