Hill Shirley Y, Shen Sa, Zezza Nicholas, Hoffman Eric K, Perlin Mark, Allan William
Department of Psychiatry, University of Pittsburgh School of Medicine, 3811 O'Hara Street, Pittsburgh, PA 15213, USA.
Am J Med Genet B Neuropsychiatr Genet. 2004 Jul 1;128B(1):102-13. doi: 10.1002/ajmg.b.30013.
Alcoholism is currently one of the most serious public health problems in the US. Lifetime prevalence rates are relatively high with one in five men and one in 12 women meeting criteria for this condition. Identification of genetic loci conferring an increased susceptibility to developing alcohol dependence could strengthen prevention efforts by informing individuals of their risk before abusive drinking ensues. Families identified through a double proband methodology have provided an exceptional opportunity for gene-finding because of the increased recurrence risks seen in these sibships. A total of 360 markers for 22 autosomes were spaced at an average distance of 9.4 cM and genotyping performed for 330 members of these multiplex families. Extensive clinical data, personality variation, and event-related potential characteristics were available for reducing heterogeneity and detecting robust linkage signals. Multipoint linkage analysis using different analytic strategies give strong support for loci on chromosomes 1, 2, 6, 7, 10, 12, 14, 16, and 17.
酗酒目前是美国最严重的公共卫生问题之一。终生患病率相对较高，五分之一的男性和十二分之一的女性符合该病的标准。确定那些会增加酒精依赖易感性的基因位点，可在酗酒行为发生之前告知个体其风险，从而加强预防工作。通过双先证者方法识别出的家庭，因其同胞手足中出现更高的复发风险，为基因寻找提供了绝佳机会。对22条常染色体的总共360个标记进行了平均间距为9.4厘摩的定位，并对这些多重家庭的330名成员进行了基因分型。有丰富的临床数据、人格变异和事件相关电位特征可用于减少异质性并检测出可靠的连锁信号。使用不同分析策略的多点连锁分析有力支持了位于1、2、6、7、10、12、14、16和17号染色体上的基因位点。
