Corresponding Author: Jaakko Kaprio, M.D., Ph.D., Department of Public Health, University of Helsinki, PO Box 41 (Mannerheimintie 172), Helsinki 00014, Finland.
Nicotine Tob Res. 2012 Feb;14(2):153-60. doi: 10.1093/ntr/ntr153. Epub 2011 Oct 29.
Chromosome 20 has previously been associated with nicotine dependence (ND) and smoking cessation. Our aim was to replicate and extend these findings.
First, a total of 759 subjects belonging to 206 Finnish families were genotyped with 18 microsatellite markers residing on chromosome 20, in order to replicate previous linkage findings. Then, the replication data were combined to an existing whole-genome linkage data resulting in a total of 1,302 genotyped subjects from 357 families. ND diagnosed by DSM-IV criteria, the Fagerström Test for Nicotine Dependence (FTND) score, and the lifetime maximum number of cigarettes smoked within a 24-hr period (MaxCigs24) were used as phenotypes in the nonparametric linkage analyses.
We replicated previously reported linkage to DSM-IV ND, with a maximum logarithm of odd (LOD) score of 3.8 on 20p11, with females contributing more (maximum LOD [MLOD] score 3.4 on 20q11) than males (MLOD score 2.6 on 20p11). With the combined sample, a suggestive LOD score of 2.3 was observed for DSM-IV ND on 20p11. Sex-specific analyses revealed that the signal was driven by females with a maximum LOD score of 3.3 (on 20q11) versus LOD score of 1.3 in males (on 20q13) in the combined sample. No significant linkage signals were obtained for FTND or MaxCigs24.
Our results provide further evidence that chromosome 20 harbors genetic variants influencing ND in adult smokers.
染色体 20 先前与尼古丁依赖（ND）和戒烟有关。我们的目的是复制和扩展这些发现。
首先，对 206 个芬兰家庭的 759 名受试者进行了总共 18 个微卫星标记的基因分型，这些标记位于染色体 20 上，以复制先前的连锁发现。然后，将复制数据与现有的全基因组连锁数据相结合，得到来自 357 个家庭的总共 1302 名基因分型的受试者。根据 DSM-IV 标准诊断的 ND、尼古丁依赖测试（FTND）评分和 24 小时内吸烟的终生最大香烟数量（MaxCigs24）被用作非参数连锁分析的表型。
我们复制了先前报道的与 DSM-IV ND 的连锁，20p11 上的最大对数奇数（LOD）得分最高为 3.8，女性的贡献（20q11 上的最大 LOD [MLOD] 得分 3.4）大于男性（20p11 上的 MLOD 得分 2.6）。在合并样本中，在 20p11 上观察到 DSM-IV ND 的提示性 LOD 得分 2.3。性别特异性分析显示，信号是由女性驱动的，在合并样本中，女性的最大 LOD 得分 3.3（在 20q11 上），而男性的 LOD 得分 1.3（在 20q13 上）。未获得 FTND 或 MaxCigs24 的显著连锁信号。
我们的结果进一步表明，染色体 20 携带影响成年吸烟者 ND 的遗传变异。
