RT Journal
A1 Hartz SM, Short SE, Saccone NL, et al
T1 INcreased genetic vulnerability to smoking at chrna5 in early-onset smokers
JF Archives of General Psychiatry
JO Archives of General Psychiatry
YR 2012
FD August 1
VO 69
IS 8
SP 854
OP 860
DO 10.1001/archgenpsychiatry.2012.124
UL http://dx.doi.org/10.1001/archgenpsychiatry.2012.124
AB 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.Data Extraction 
                  Uniform statistical analysis scripts were run locally. Starting with 94 050 ever-smokers from 43 studies, 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 heavy vs 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.