6533b852fe1ef96bd12aa462
RESEARCH PRODUCT
Meta-analysis and imputation refines the association of 15q25 with smoking quantity.
Mark J. CaulfieldPaul ScheetRuth J. F. LoosOzren PolasekVincent MooserMichael WittigStephen E. EpsteinJames F. WilsonGonçalo R. AbecasisJennifer E. HuffmanAugusto D. PichardMary Susan BurnettRajesh RawalFederica TozziNilesh J. SamaniHans J. GrabeRobert L. WilenskyMiles ParkesJing Hua ZhaoJaspal S. KoonerDaniel J. RaderWade H. BerrettiniPer BakkeRobert W. MahleyAstrid PetersmannAlan F. WrightKenneth M. KentLowell F. SatlerAlistair S. HallXin YuanHakon HakonarsonHenry VölzkePeter VollenweiderXiangjun XiaoJohn B. VincentJoseph M. LindsayScott M. GrundyChristopher G. MathewCaroline HaywardSusan CampbellJohn R. ThompsonAlexander TeumerInês BarrosoDavid SchlessingerJack SatsangiBenjamin J. WrightCarl A. AndersonFabio BusoneroJames L. KennedyHarry CampbellDan RujescuAnne BartonH.-erich WichmannPhilip J. BarterVeronique VitartAntonio TerraccianoRuth McphersonS. HorstmannAnna F. DominiczakMartin PreisigSusanne LucaeDavid St ClairLina ZgagaJane WorthingtonJoseph M. DevaneyWendy ThomsonAnne FarmerAntero KesäniemiUlrich JohnTariq AhmadWilliam H. MatthaiJason Z. LiuMuredach P. ReillyIvana KolcicIgor RudanIgor RudanNorbert DahmenMartin FarrallAnthony J. BalmforthNicholas J. WarehamSteve EyreT. BruecklKay-tee KhawLiming QuChristopher W. KnouffSarah H. WildPatricia B. MunroeClaudia LaminaDawn M. WaterworthJohn StraussJohn C. ChambersMarcus IsingRichard O. DayAmund GulsvikGérard WaeberArne SchäferAndre FrankeClyde FrancksClyde FrancksPierandrea MugliaMingyao LiPeter McguffinKeith MatthewsManuela UdaSreekumar G. PillaiJonathan MarchiniLefkos T. MiddletonRon Waksmansubject
Genetics0303 health scienceseducation.field_of_study/dk/atira/pure/subjectarea/asjc/1300/1311PopulationSingle-nucleotide polymorphismGenome-wide association studyLocus (genetics)BiologyArticle3. Good health03 medical and health sciences0302 clinical medicineGenome-Wide Association; Nicotine Dependence; Lung-Cancer; Susceptibility Locus; Risk-Factors; Disease; Genes; SNPS; Colaus StudyGeneticsSNP1000 Genomes ProjectAlleleeducation030217 neurology & neurosurgeryImputation (genetics)genome-wide association study; smoking initiation; smoking quantity030304 developmental biologydescription
Smoking is a leading global cause of disease and mortality(1). We established the Oxford-GlaxoSmithKline study (Ox-GSK) to perform a genome-wide meta-analysis of SNP association with smoking-related behavioral traits. Our final data set included 41,150 individuals drawn from 20 disease, population and control cohorts. Our analysis confirmed an effect on smoking quantity at a locus on 15q25 (P = 9.45 x 10(-19)) that includes CHRNA5, CHRNA3 and CHRNB4, three genes encoding neuronal nicotinic acetylcholine receptor subunits. We used data from the 1000 Genomes project to investigate the region using imputation, which allowed for analysis of virtually all common SNPs in the region and offered a fivefold increase in marker density over HapMap2 (ref. 2) as an imputation reference panel. Our fine-mapping approach identified a SNP showing the highest significance, rs55853698, located within the promoter region of CHRNA5. Conditional analysis also identified a secondary locus (rs6495308) in CHRNA3.
| year | journal | country | edition | language |
|---|---|---|---|---|
| 2010-05-01 | Nature genetics |