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Increased genetic vulnerability to smoking at CHRNA5 in early-onset smokers.

TitleIncreased genetic vulnerability to smoking at CHRNA5 in early-onset smokers.
Publication TypeJournal Article
Year of Publication2012
AuthorsHartz SM, Short SE, Saccone NL, et al.
Secondary AuthorsBierut LJ
JournalArch Gen Psychiatry
Volume69
Issue8
Pagination854-60
Date Published2012 Aug
ISSN1538-3636
KeywordsAdolescent, Adolescent Development, Adult, Age of Onset, Europe, Female, Gene-Environment Interaction, Genetic Association Studies, Genetic Predisposition to Disease, Humans, Male, Nerve Tissue Proteins, Nicotine, Polymorphism, Single Nucleotide, Receptors, Nicotinic, Severity of Illness Index, Smoking, Tobacco Use Disorder
Abstract

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.

DOI10.1001/archgenpsychiatry.2012.124
Alternate JournalArch Gen Psychiatry
PubMed ID22868939
PubMed Central IDPMC3482121
Grant ListR01 HL089651 / HL / NHLBI NIH HHS / United States
R01 MH60870 / MH / NIMH NIH HHS / United States
N01 HR046002 / HR / NHLBI NIH HHS / United States
K07 CA118412 / CA / NCI NIH HHS / United States
R01 MH81800 / MH / NIMH NIH HHS / United States
R01 MH061675 / MH / NIMH NIH HHS / United States
U01HG004446 / HG / NHGRI NIH HHS / United States
U01 MH046318-08 / MH / NIMH NIH HHS / United States
DA019951 / DA / NIDA NIH HHS / United States
U19 CA148127 / CA / NCI NIH HHS / United States
U01DA02830 / DA / NIDA NIH HHS / United States
U01HG004438 / HG / NHGRI NIH HHS / United States
K01DA19498 / DA / NIDA NIH HHS / United States
R01 NS045012 / NS / NINDS NIH HHS / United States
U01 MH046276-08 / MH / NIMH NIH HHS / United States
U01 HG004438 / HG / NHGRI NIH HHS / United States
R01 DA003706 / DA / NIDA NIH HHS / United States
R01 CA060691 / CA / NCI NIH HHS / United States
K05 AA017688 / AA / NIAAA NIH HHS / United States
N01 AG012100 / AG / NIA NIH HHS / United States
R01 DA012690 / DA / NIDA NIH HHS / United States
R01 DE012101 / DE / NIDCR NIH HHS / United States
U01 HG004446 / HG / NHGRI NIH HHS / United States
R24 HD041020 / HD / NICHD NIH HHS / United States
R01 MH60879 / MH / NIMH NIH HHS / United States
R01 DA017932 / DA / NIDA NIH HHS / United States
R01 MH59566 / MH / NIMH NIH HHS / United States
K01 DA024758 / DA / NIDA NIH HHS / United States
U01 MH79470 / MH / NIMH NIH HHS / United States
R01 AA11330 / AA / NIAAA NIH HHS / United States
U01HG004738 / HG / NHGRI NIH HHS / United States
U01 MH046276 / MH / NIMH NIH HHS / United States
R21 DA033827 / DA / NIDA NIH HHS / United States
N01-PC35146 / PC / NCI NIH HHS / United States
N01-AG-1-2109 / AG / NIA NIH HHS / United States
R01 DA012849 / DA / NIDA NIH HHS / United States
MH46289 / MH / NIMH NIH HHS / United States
R01 MH59588 / MH / NIMH NIH HHS / United States
U01 HG006513 / HG / NHGRI NIH HHS / United States
DA12854 / DA / NIDA NIH HHS / United States
K08 DA030398 / DA / NIDA NIH HHS / United States
R21DA033827 / DA / NIDA NIH HHS / United States
R01NS45012 / NS / NINDS NIH HHS / United States
Z99 AG999999 / / Intramural NIH HHS / United States
P01 CA089392 / CA / NCI NIH HHS / United States
K01DA24758 / DA / NIDA NIH HHS / United States
TL1 RR024995 / RR / NCRR NIH HHS / United States
R01 DE014899 / DE / NIDCR NIH HHS / United States
R01 DA025888 / DA / NIDA NIH HHS / United States
U01 MH079469 / MH / NIMH NIH HHS / United States
R01 MH59586 / MH / NIMH NIH HHS / United States
R01 DA12849 / DA / NIDA NIH HHS / United States
R01 MH59587 / MH / NIMH NIH HHS / United States
R56 DA012854 / DA / NIDA NIH HHS / United States
R03 AG035146 / AG / NIA NIH HHS / United States
UL1RR024992 / RR / NCRR NIH HHS / United States
UL1 RR024992 / RR / NCRR NIH HHS / United States
R01 DA026911 / DA / NIDA NIH HHS / United States
R01 MH59565 / MH / NIMH NIH HHS / United States
R01 MH067257 / MH / NIMH NIH HHS / United States
K08 DA032680 / DA / NIDA NIH HHS / United States
R21 DA027070 / DA / NIDA NIH HHS / United States
R01 MH060870 / MH / NIMH NIH HHS / United States
R01 MH081800 / MH / NIMH NIH HHS / United States
R01 MH61675 / MH / NIMH NIH HHS / United States
R01 MH059571 / MH / NIMH NIH HHS / United States
HHSN268200782096C / HG / NHGRI NIH HHS / United States
R01 MH059565 / MH / NIMH NIH HHS / United States
R01DA026911 / DA / NIDA NIH HHS / United States
U01 NS069208 / NS / NINDS NIH HHS / United States
R01 DA03706 / DA / NIDA NIH HHS / United States
U01 MH079470 / MH / NIMH NIH HHS / United States
R01 MH59571 / MH / NIMH NIH HHS / United States
MH46318 / MH / NIMH NIH HHS / United States
R01 MH059587 / MH / NIMH NIH HHS / United States
U01-DE018903 / DE / NIDCR NIH HHS / United States
K02 AA018755 / AA / NIAAA NIH HHS / United States
090532 / / Wellcome Trust / United Kingdom
ZIA AG000196-03 / / Intramural NIH HHS / United States
R01 AA011330 / AA / NIAAA NIH HHS / United States
R01 DA012854 / DA / NIDA NIH HHS / United States
R01DA25888 / DA / NIDA NIH HHS / United States
R01 MH059586 / MH / NIMH NIH HHS / United States
R01 AA017535 / AA / NIAAA NIH HHS / United States
U01 MH79469 / MH / NIMH NIH HHS / United States
U01 MH046289 / MH / NIMH NIH HHS / United States
UL1 TR000448 / TR / NCATS NIH HHS / United States
K08 DA019951 / DA / NIDA NIH HHS / United States
K02DA021237 / DA / NIDA NIH HHS / United States
K02 DA021237 / DA / NIDA NIH HHS / United States
R01CA060691 / CA / NCI NIH HHS / United States
T32 MH014677 / MH / NIMH NIH HHS / United States
U01 DE018903 / DE / NIDCR NIH HHS / United States
U01 HG004436 / HG / NHGRI NIH HHS / United States
N01PC35145 / CA / NCI NIH HHS / United States
TL1 TR000449 / TR / NCATS NIH HHS / United States
R01 MH67257 / MH / NIMH NIH HHS / United States
K01 DA019498 / DA / NIDA NIH HHS / United States
R01 DA018673 / DA / NIDA NIH HHS / United States
R01 MH059566 / MH / NIMH NIH HHS / United States
R01 DA12690 / DA / NIDA NIH HHS / United States
U01 HG004738 / HG / NHGRI NIH HHS / United States
U10 AA008401 / AA / NIAAA NIH HHS / United States
R01 MH059588 / MH / NIMH NIH HHS / United States
U01 MH046318 / MH / NIMH NIH HHS / United States
KL2 RR024994 / RR / NCRR NIH HHS / United States
R01HL089651-01 / HL / NHLBI NIH HHS / United States
N01-PC35145 / PC / NCI NIH HHS / United States
R21DA027070 / DA / NIDA NIH HHS / United States
U54 RR020278 / RR / NCRR NIH HHS / United States
U01 DA020830 / DA / NIDA NIH HHS / United States
U01 MH046289-08 / MH / NIMH NIH HHS / United States
R01 MH060879 / MH / NIMH NIH HHS / United States
ZIA AG000196-04 / / Intramural NIH HHS / United States
KL2 TR000450 / TR / NCATS NIH HHS / United States