Department of Health Policy and Management, Gillings School of Public Health, University of North Carolina–Chapel Hill, NC, USA.
JAMA Psychiatry. 2013 May;70(5):534-42. doi: 10.1001/jamapsychiatry.2013.736.
Genome-wide hypothesis-free discovery methods have identified loci that are associated with heavy smoking in adulthood. Research is needed to understand developmental processes that link newly discovered genetic risks with adult heavy smoking.
To test how genetic risks discovered in genome-wide association studies of adult smoking influence the developmental progression of smoking behavior from initiation through conversion to daily smoking, progression to heavy smoking, nicotine dependence, and struggles with cessation.
A 38-year, prospective, longitudinal study of a representative birth cohort.
The Dunedin Multidisciplinary Health and Development Study of New Zealand.
The study included 1037 male and female participants.
We assessed genetic risk with a multilocus genetic risk score. The genetic risk score was composed of single-nucleotide polymorphisms identified in 3 meta-analyses of genome-wide association studies of smoking quantity phenotypes.
Smoking initiation, conversion to daily smoking, progression to heavy smoking, nicotine dependence (Fagerström Test of Nicotine Dependence), and cessation difficulties were evaluated at 8 assessments spanning the ages of 11 to 38 years.
Genetic risk score was unrelated to smoking initiation. However, individuals at higher genetic risk were more likely to convert to daily smoking as teenagers, progressed more rapidly from smoking initiation to heavy smoking, persisted longer in smoking heavily, developed nicotine dependence more frequently, were more reliant on smoking to cope with stress, and were more likely to fail in their cessation attempts. Further analysis revealed that 2 adolescent developmental phenotypes-early conversion to daily smoking and rapid progression to heavy smoking-mediated associations between the genetic risk score and mature phenotypes of persistent heavy smoking, nicotine dependence, and cessation failure. The genetic risk score predicted smoking risk over and above family history.
Initiatives that disrupt the developmental progression of smoking behavior among adolescents may mitigate genetic risks for developing adult smoking problems. Future genetic research may maximize discovery potential by focusing on smoking behavior soon after smoking initiation and by studying young smokers.
全基因组无假设发现方法已经确定了与成年后重度吸烟相关的基因座。需要研究将新发现的遗传风险与成人重度吸烟联系起来的发育过程。
测试成人吸烟全基因组关联研究中发现的遗传风险如何影响吸烟行为从开始到转为每日吸烟、进展到重度吸烟、尼古丁依赖以及戒烟困难的发展过程。
一项对新西兰达尼丁多学科健康和发展研究的代表性出生队列的 38 年前瞻性纵向研究。
达尼丁多学科健康和发展研究。
该研究包括 1037 名男性和女性参与者。
我们使用多基因风险评分评估遗传风险。遗传风险评分由 3 项吸烟量表型全基因组关联研究荟萃分析中确定的单核苷酸多态性组成。
在 8 次评估中评估吸烟开始、转为每日吸烟、进展为重度吸烟、尼古丁依赖（尼古丁依赖测试）和戒烟困难，评估年龄从 11 岁到 38 岁。
遗传风险评分与吸烟开始无关。然而，处于较高遗传风险的个体在青少年时期更有可能转为每日吸烟，从吸烟开始到重度吸烟的进展速度更快，吸烟时间更长，尼古丁依赖更频繁，更依赖吸烟来应对压力，并且更有可能戒烟失败。进一步的分析表明，2 种青少年发育表型-早期转为每日吸烟和快速进展到重度吸烟-介导了遗传风险评分与持续重度吸烟、尼古丁依赖和戒烟失败的成熟表型之间的关联。遗传风险评分预测了吸烟风险，超过了家族史。
破坏青少年吸烟行为发展过程的干预措施可能会减轻成年后吸烟问题的遗传风险。未来的遗传研究可能会通过关注吸烟开始后不久的吸烟行为并研究年轻吸烟者来最大限度地提高发现潜力。
