Genetic variability of smoking persistence in African Americans.
Genetic variability of smoking persistence in African Americans.
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DOI：
10.1158/1940-6207.capr-10-0362
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发表时间：
2011-05
期刊：
影响因子：
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通讯作者：
Jorgenson E
中科院分区：
文献类型：
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作者：
Hamidovic A;Kasberger JL;Young TR;Goodloe RJ;Redline S;Buxbaum SG;Benowitz NL;Bergen AW;Butler KR;Franceschini N;Gharib SA;Hitsman B;Levy D;Meng Y;Papanicolaou GJ;Preis SR;Spring B;Styn MA;Tong EK;White WB;Wiggins KL;Jorgenson E
到目前为止，大多数吸烟行为的遗传关联分析都是在欧洲血统的人群中进行的，其中许多研究都集中在测量吸烟量的表型上，即每天的吸烟量。在具有不同连锁不平衡（LD）模式和替代表型的不同人群中进行的其他关联研究，例如在大型心血管风险研究中测量的较大吸烟期内的间歇性戒烟期的总烟草暴露，可以帮助寻找与吸烟行为相关的变异。出于这些原因，我们使用包括2100个基因的基因分型阵列进行了关联分析，以分析来自社区动脉粥样硬化风险（ARIC）研究的非裔美国人参与者的吸烟持续性。位于脑源性神经营养因子（BDNF）3' UTR下游约4Kb的基因座显著影响吸烟持续性。此外，15q25.1上编码烟碱乙酰胆碱受体亚基（CHRNA 5-CHRNA 3-CHRNB 4）的基因簇中的独立变体rs 12915366和rs 12914385也与该非裔美国人受试者样本中的表型相关。据我们所知，这是第一项更广泛地评估非裔美国人基因组的研究，因为之前对该人群吸烟行为的研究数量有限，仅包括对单个基因组区域的评估。
To date, most genetic association analyses of smoking behaviors have been conducted in populations of European ancestry and many of these studies focused on the phenotype that measures smoking quantity, i.e. cigarettes per day. Additional association studies in diverse populations with different linkage disequilibrium (LD) patterns and an alternate phenotype, such as total tobacco exposure which accounts for intermittent periods of smoking cessation within a larger smoking period as measured in large cardiovascular risk studies, can aid the search for variants relevant to smoking behavior. For these reasons, we undertook an association analysis using a genotyping array that includes 2100 genes to analyze smoking persistence in unrelated African-American participants from The Atherosclerosis Risk in Communities (ARIC) study. A locus located ~ 4 Kb downstream from the 3’ UTR of the Brain-Derived Neurotrophic Factor (BDNF) significantly influenced smoking persistence. In addition, independent variants rs12915366 and rs12914385 in the cluster of genes encoding nicotinic acetylcholine receptor subunits (CHRNA5-CHRNA3-CHRNB4) on 15q25.1 were also associated with the phenotype in this sample of African American subjects. To our knowledge, this is the first study to more extensively evaluate the genome in the African American population as a limited number of previous studies of smoking behavior in this population included evaluations of only single genomic regions.