Genome-wide meta-analyses identify multiple loci associated with smoking behavior

• Authors: FURBERG Helena; KIM Yun Lung; DACKOR J.; BOERWINKLE E.; FRANCESCHINI N.; ARDISSINO D.; BERNARDINELLI L.; MANNUCCI P.; MAURI F.; MERLINI P.; ABSHER D.; ASSIMES T.; FORTMANN S.; IRIBARREN C.; KNOWLES J.; QUERTERMOUS T.; FERRUCCI L.; TANAKA T.; BIS J.; FURBERG C.; HARITUNIANS T.; MCKNIGHT B.; PSATY B.; TAYLOR K.; THACKER E.; ALMGREN P.; GROOP L.; LADENVALL C.; BOEHNKE M.; JACKSON A.; MOHLKE K.; STRINGHAM H.; TUOMILEHTO J.; BENJAMIN E.; HWANG S.; LEVY D.; PREIS S.; VASAN R.; DUAN J.; GEJMAN P.; LEVINSON D.; SANDERS A.; SHI J.; LIPS E.; MCKAY J.; AGUDO A.; BARZAN L.; BENCKO V.; BENHAMOU S.; CASTELLSAGUE X.; CANOVA C.; CONWAY D.; FABIANOVA E.; FORETOVÁ Lenka; JANOUT V.; HEALY C.; HOLCATOVA I.; KJAERHEIM K.; LAGIOU P.; LISSOWSKA J.; LOWRY R.; MACFARLANE T.; MATES D.; RICHIARDI L.; RUDNAI P.; SZESZENIA-DABROWSKA N.; ZARIDZE D.; ZNAOR A.; LATHROP M.; BRENNAN P.; BANDINELLI S.; FRAYLING T.; GURALNIK J.; MILANESCHI Y.; PERRY J.; ALTSHULER D.; ELOSUA R.; KATHIRESAN S.; LUCAS G.; MELANDER O.; O'DONNELL Ch.; SALOMAA V.; SCHWARTZ S.; VOIGHT B.; PENNINX B.; SMIT J.; VOGELZANGS J.; BOOMSMA D.; DE GEUS E.J.C.; VINK J.; WILLEMSEN G.; CHANOCK S.; GU F.; HANKINSON S.; HUNTER D.; HOFMAN A.; TIEMEIER H.; PARE G.; RIDKER P.; LI M.; MAES H.; AUDRAIN-MCGOVERN J.; POSTHUMA D.; THORNTON L.; LERMAN C.; KAPRIO J.; ROSE J.; IOANNIDIS J.; KRAFT P.; LIN D.; SULLIVAN P.; EVERETT B.M.; CHASMAN D.; WALTER S.; VAN DUIJN C.; UITTERLINDEN A.D.
• Year of publication: 2010
• Type: Article in Periodical
• Magazine / Source: Nature genetics
• MU Faculty or unit: Faculty of Medicine
• Doi: https://doi.org/10.1038/ng.571
• Field: Oncology and hematology
• Keywords: NICOTINE DEPENDENCE; ENVIRONMENTAL-FACTORS; IMPUTATION; GENES; VARIANTS; DISEASES; SETS
• Description: Consistent but indirect evidence has implicated genetic factors in smoking behavior1,2. We report meta-analyses of several smoking phenotypes within cohorts of the Tobacco and Genetics Consortium (n = 74,053). We also partnered with the European Network of Genetic and Genomic Epidemiology (ENGAGE) and Oxford-GlaxoSmithKline (Ox-GSK) consortia to follow up the 15 most significant regions (n > 140,000). We identified three loci associated with number of cigarettes smoked per day. The strongest association was a synonymous 15q25 SNP in the nicotinic receptor gene CHRNA3 (rs1051730[A], b = 1.03, standard error (s.e.) = 0.053, beta = 2.8 x 10(-73)). Two 10q25 SNPs (rs1329650[G], b = 0.367, s. e. = 0.059, beta = 5.7 x 10(-10); and rs1028936[A], b = 0.446, s. e. = 0.074, beta = 1.3 x 10(-9)) and one 9q13 SNP in EGLN2 (rs3733829[G], b = 0.333, s. e. = 0.058, P = 1.0 x 10(-8)) also exceeded genome-wide significance for cigarettes per day. For smoking initiation, eight SNPs exceeded genome-wide significance, with the strongest association at a nonsynonymous SNP in BDNF on chromosome 11 (rs6265[C], odds ratio (OR) = 1.06, 95% confidence interval (Cl) 1.04-1.08, P = 1.8 x 10(-8)). One SNP located near DBH on chromosome 9 (rs3025343[G], OR = 1.12, 95% Cl 1.08-1.18, P = 3.6 x 10(-8)) was significantly associated with smoking cessation.