Meta-analysis of 15 genome-wide linkage scans of smoking behavior.
Meta-analysis of 15 genome-wide linkage scans of smoking behavior.
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DOI：
10.1016/j.biopsych.2009.08.028
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发表时间：
2010-01-01
影响因子：
10.6
通讯作者：
Yang, Bao-Zhu
中科院分区：
文献类型：
--
作者：
Han, Shizhong;Gelernter, Joel;Luo, Xingguang;Yang, Bao-Zhu
吸烟行为的遗传因素已经得到了很好的证实。为了确定增加吸烟行为风险的基因座，使用各种吸烟行为评估进行了许多全基因组连锁扫描。已经确定了许多假定的易感基因座，但只有几个在独立研究中重复。我们使用基因组搜索荟萃分析(GSMA)通过汇集所有可用的关于吸烟行为的独立基因组扫描结果来识别风险基因。此外，为了最大限度地减少基因座的异质性，对吸烟行为进行了亚组分析，采用尼古丁依赖的Fagerstrom检验(FTND)和24小时内最大吸烟量(MaxCigs24)。欧洲血统的样本也分别进行了分析。总共有15个基因组扫描结果可供分析，其中包括3404个家庭，10253名受试者。总体而言，所有吸烟行为的初级GSMA在染色体17q24.3-q25.3(Psr=0.001)上发现了一个全基因组范围的暗示连锁。对欧洲血统样本(625个家系，1,878名受试者)的二次分析发现，5q33.1-5q35.2(Psr=0.0076)存在全基因组范围的暗示连锁；MaxCigs24(966个家系，3,273名受试者)的亚群分析发现在20q13.12-q13.32(Psr=0.00041，POR=0.048)存在全基因组显著连锁，其中有一个强有力支持的ND候选基因CHRNA4。本研究中确定的区域值得密切关注，将有助于将来的候选基因鉴定或靶基因重测序研究。
A genetic contribution to smoking behavior is well established. To identify loci that increase the risk for smoking behavior, many genomewide linkage scans have been performed using various smoking behavior assessments. Numerous putative susceptibility loci have been identified, but only a few of these were replicated in independent studies. We used genome seach meta-analysis (GSMA) to identify risk loci by pooling all available independent genome scan results on smoking behavior. Additionally, to minimize locus heterogeneity, subgroup analyses of the smoking behavior assessed by the Fagerstrom test for nicotine dependence (FTND) and maximum number of cigarettes smoked in a 24-hour period (MaxCigs24) were carried out. Samples of European ancestry were also analyzed separately. A total number of 15 genome scan results were available for analysis, including 3404 families with 10,253 subjects. Overall, the primary GSMA across all smoking behavior identified a genomewide suggestive linkage in chromosome 17q24.3–q25.3 (PSR=0.001). A secondary analysis of FTND in European-ancestry samples (625 families with 1878 subjects) detected a genomewide suggestive linkage in 5q33.1–5q35.2(PSR=0.0076).Subgroup analysis of MaxCigs24 (966 families with 3273 subjects) identified a genomewide significant linkage in 20q13.12–q13.32 (PSR=0.00041, POR=0.048), where a strongly supported ND candidate gene, CHRNA4, is located. The regions identified in the current study deserve close attention and will be helpful for candidate gene identification or target resequencing studies in the future.
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影响因子：
3.7
作者：
Caporaso N;Gu F;Chatterjee N;Sheng-Chih J;Yu K;Yeager M;Chen C;Jacobs K;Wheeler W;Landi MT;Ziegler RG;Hunter DJ;Chanock S;Hankinson S;Kraft P;Bergen AW
通讯作者：
Bergen AW
影响因子：
7.6
作者：
Beuten, J;Payne, TJ;Li, MD
通讯作者：
Li, MD
影响因子：
10.6
作者：
Gelernter, Joel;Panhuysen, Carolien;Kranzler, Henry R.
通讯作者：
Kranzler, Henry R.
影响因子：
2
作者：
Bierut, LJ;Rice, JP;Reich, T
通讯作者：
Reich, T
影响因子：
5
作者：
Forabosco, P.;Gorman, J. D.;Criswell, L. A.
通讯作者：
Criswell, L. A.