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Multiple distinct CHRNB 3– CHRNA 6 variants are genetic risk factors for nicotine dependence in A frican A mericans and E uropean A mericans
Author(s) -
Culverhouse Robert C.,
Johnson Eric O.,
Breslau Naomi,
Hatsukami Dorothy K.,
Sadler Brooke,
Brooks Andrew I.,
Hesselbrock Victor M.,
Schuckit Marc A.,
Tischfield Jay A.,
Goate Alison M.,
Saccone Nancy L.,
Bierut Laura J.
Publication year - 2014
Publication title -
addiction
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.424
H-Index - 193
eISSN - 1360-0443
pISSN - 0965-2140
DOI - 10.1111/add.12478
Subject(s) - nicotine dependence , nicotine , genetic variants , medicine , genetics , clinical psychology , psychology , demography , psychiatry , biology , genotype , gene , sociology
Aims Studies have shown association between common variants in the α6–β3 nicotinic receptor subunit gene cluster and nicotine dependence in E uropean ancestry populations. We investigate whether this generalizes to A frican A mericans, whether the association is specific to nicotine dependence and whether this region contains additional genetic contributors to nicotine dependence. Design We examined consistency of association across studies and race between the α6β3 nicotinic receptor subunit locus and nicotine, alcohol, marijuana and cocaine dependence in three independent studies. Setting U nited S tates of A merica. Participants E uropean A mericans and A frican A mericans from three case–control studies of substance dependence. Measurements Subjects were evaluated using the S emi‐ S tructured A ssessment for the G enetics of A lcoholism. Nicotine dependence was determined using the F agerström T est for N icotine D ependence. Findings The single nucleotide polymorphism rs13273442 was associated significantly with nicotine dependence across all three studies in both ancestry groups [odds ratio ( OR ) = 0.75, P = 5.8 × 10 −4 E uropean A mericans; OR = 0.80, P = 0.05 A frican A mericans]. No other substance dependence was associated consistently with this variant in either group. Another SNP in the region, rs4952, remains modestly associated with nicotine dependence in the combined data after conditioning on rs13273442. Conclusions The common variant rs13273442 in the CHRNB 3– CHNRA 6 region is associated significantly with nicotine dependence in E uropean A mericans and A frican A mericans across studies recruited for nicotine, alcohol and cocaine dependence. Although these data are modestly powered for other substances, our results provide no evidence that correlates of rs13273442 represent a general substance dependence liability. Additional variants probably account for some of the association of this region to nicotine dependence.