Context: Recent studies have shown an association between cigarettes per day (CPD) and a nonsynonymous single-nucleotide polymorphism in CHRNA5, rs16969968. Objective: To determine whether the association between rs16969968 and smoking is modified by age at onset of regular smoking. Data Sources: Primary data. Study Selection: Available genetic studies containing measures of CPD and the genotype of rs16969968 or its proxy. DataExtraction: Uniform statistical analysis scripts were runlocally. Startingwith94 050ever-smokersfrom43studies, we extracted the heavy smokers (CPD>20) and light smokers (CPD ≤10) with age-at-onset information, reducing the sample size to 33 348. Each study was stratified into early-onset smokers (age at onset ≤16 years) and late-onset smokers (age at onset >16 years), and a logistic regression of heavyvs light smoking with the rs16969968 genotype was computed for each stratum. Meta-analysis was performed within each age-at-onset stratum. Data Synthesis: Individuals with 1 risk allele at rs16969968 who were early-onset smokers were significantly more likely to be heavy smokers in adulthood (odds ratio [OR]=1.45; 95% CI, 1.36-1.55; n=13 843) than were carriers of the risk allele who were late-onset smokers (OR=1.27; 95% CI, 1.21-1.33, n=19 505) (P=.01). Conclusion: These results highlight an increased genetic vulnerability to smoking in early-onset smokers. ©2012 American Medical Association. All rights reserved.
CITATION STYLE
S.M., H., S.E., S., N.L., S., R., C., L., C., T.-H., S.-A., … L.J., B. (2012). Increased genetic vulnerability to smoking at CHRNA5 in early-onset smokers. Archives of General Psychiatry, 69(8), 854–861. Retrieved from http://www.embase.com/search/results?subaction=viewrecord&from=export&id=L365531253 http://archpsyc.jamanetwork.com/data/Journals/PSYCH/24738/yma120011_854_861.pdf http://dx.doi.org/10.1001/archgenpsychiatry.2012.124
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