Loukola A, Broms U, Maunu H, Widén E, Heikkilä K, Siivola M, Salo A, Pergadia M L, Nyman E, Sammalisto S, Perola M, Agrawal A, Heath A C, Martin N G, Madden P A F, Peltonen L, Kaprio J
Department of Molecular Medicine, National Public Health Institute, Helsinki, Finland.
Pharmacogenomics J. 2008 Jun;8(3):209-19. doi: 10.1038/sj.tpj.6500464. Epub 2007 Jun 5.
The significant worldwide health burden introduced by tobacco smoking highlights the importance of studying the genetic determinants of smoking behavior and the key factor sustaining compulsive smoking, that is, nicotine dependence (ND). We have here addressed the genetic background of smoking in a special study sample of twins, harmonized for early life events and specifically ascertained for smoking from the nationwide twin cohort of the genetically unique population of Finland. The twins and their families were carefully examined for extensive phenotype profiles and a genome-wide scan was performed to identify loci behind the smoking status, ND and the comorbid phenotype of ND and alcohol use in 505 individuals from 153 families. We replicated previous linkage findings on 10q (max logarithm of the odds (LOD) 3.12) for a smoker phenotype, and on 7q and 11p (max LOD 2.50, and 2.25, respectively) for the ND phenotype. The loci linked for ND also showed evidence for linkage for the comorbid phenotype. Our study provides confirmatory evidence for the involvement of these genome regions in the genetic etiology of smoking behavior and ND and for the first time associates drinking and smoking to a shared locus on 10q.
吸烟给全球带来的重大健康负担凸显了研究吸烟行为的遗传决定因素以及维持强迫性吸烟的关键因素（即尼古丁依赖，ND）的重要性。我们在此针对一个特殊的双胞胎研究样本探讨了吸烟的遗传背景，该样本在早期生活事件方面进行了协调，并从芬兰基因独特人群的全国双胞胎队列中专门确定了吸烟情况。对双胞胎及其家庭进行了仔细检查以获取广泛的表型特征，并对来自153个家庭的505名个体进行了全基因组扫描，以确定吸烟状况、尼古丁依赖以及尼古丁依赖与酒精使用的共病表型背后的基因座。我们重复了先前关于吸烟者表型在10q上的连锁发现（最大优势对数（LOD）为3.12），以及关于尼古丁依赖表型在7q和11p上的连锁发现（最大LOD分别为2.50和2.25）。与尼古丁依赖相关的基因座也显示出与共病表型存在连锁的证据。我们的研究为这些基因组区域参与吸烟行为和尼古丁依赖的遗传病因提供了确证，并首次将饮酒和吸烟与10q上的一个共享基因座联系起来。
