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Summary: 436 VOLUME 42 | NUMBER 5 | MAY 2010 Nature GeNetics
l e t t e r s
Smokingisaleadingglobalcauseofdiseaseandmortality1.
WeestablishedtheOxford-GlaxoSmithKlinestudy(Ox-GSK)to
performagenome-widemeta-analysisofSNPassociationwith
smoking-relatedbehavioraltraits.Ourfinaldatasetincluded
41,150individualsdrawnfrom20disease,populationandcontrol
cohorts.Ouranalysisconfirmedaneffectonsmokingquantity
atalocuson15q25(P=9.45×10-19)thatincludesCHRNA5,
CHRNA3andCHRNB4,threegenesencodingneuronalnicotinic
acetylcholinereceptorsubunits.Weuseddatafromthe1000
Genomesprojecttoinvestigatetheregionusingimputation,which
allowedforanalysisofvirtuallyallcommonSNPsintheregionand
offeredafivefoldincreaseinmarkerdensityoverHapMap2(ref.2)
asanimputationreferencepanel.Ourfine-mappingapproach
identifiedaSNPshowingthehighestsignificance,rs55853698,
locatedwithinthepromoterregionofCHRNA5.Conditional
analysisalsoidentifiedasecondarylocus(rs6495308)inCHRNA3.
Smoking behavior and nicotine dependence are multifactorial traits
with substantial genetic influences3. There is an urgent need to better
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