title: Gene-centric analysis of serum cotinine levels in African and European American populations.
abstract: To date, most genetic association studies of tobacco use have been conducted in European American subjects using the phenotype of smoking quantity (cigarettes per day). However, smoking quantity is a very imprecise measure of exposure to tobacco smoke constituents. Analyses of alternate phenotypes and populations may improve our understanding of tobacco addiction genetics. Cotinine is the major metabolite of nicotine, and measuring serum cotinine levels in smokers provides a more objective measure of nicotine dose than smoking quantity. Previous genetic association studies of serum cotinine have focused on individual genes. We conducted a genetic association study of the biomarker in African American (N=365) and European American (N=315) subjects from the Coronary Artery Risk Development in Young Adults study using a chip containing densely-spaced tag SNPs in ∼2100 genes. We found that rs11187065, located in the non-coding region (intron 1) of insulin-degrading enzyme (IDE), was the most strongly associated SNP (p=8.91 × 10(-6)) in the African American cohort, whereas rs11763963, located on chromosome 7 outside of a gene transcript, was the most strongly associated SNP in European Americans (p=1.53 × 10(-6)). We then evaluated how the top variant association in each population performed in the other group. We found that the association of rs11187065 in IDE was also associated with the phenotype in European Americans (p=0.044). Our top SNP association in European Americans, rs11763963 was non-polymorphic in our African American sample. It has been previously shown that psychostimulant self-administration is reduced in animals with lower insulin because of interference with dopamine transmission in the brain reward centers. Our finding provides a platform for further investigation of this, or additional mechanisms, involving the relationship between insulin and self-administered nicotine dose.
authors.affiliation: Department of Preventive Medicine, Northwestern University, Chicago, IL 60611, USA. a-hamidovic@northwestern.edu
authors.forename: Ajna
authors.initials: A
authors.lastname: Hamidovic
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Goodloe
authors.forename: Andrew W
authors.initials: AW
authors.lastname: Bergen
authors.forename: Neal L
authors.initials: NL
authors.lastname: Benowitz
authors.forename: Mindi A
authors.initials: MA
authors.lastname: Styn
authors.forename: Jay L
authors.initials: JL
authors.lastname: Kasberger
authors.forename: Helene
authors.initials: H
authors.lastname: Choquet
authors.forename: Taylor R
authors.initials: TR
authors.lastname: Young
authors.forename: Yan
authors.initials: Y
authors.lastname: Meng
authors.forename: Cameron
authors.initials: C
authors.lastname: Palmer
authors.forename: Mark
authors.initials: M
authors.lastname: Pletcher
authors.forename: Stefan
authors.initials: S
authors.lastname: Kertesz
authors.forename: Brian
authors.initials: B
authors.lastname: Hitsman
authors.forename: Bonnie
authors.initials: B
authors.lastname: Spring
authors.forename: Eric
authors.initials: E
authors.lastname: Jorgenson
mesh_terms: D000293:Adolescent; D000328:Adult; D044383:Black People / Q000235:genetics*; D015331:Cohort Studies; D003367:Cotinine / Q000097:blood*; D005260:Female; D020022:Genetic Predisposition to Disease / Q000208:ethnology / Q000235:genetics*; D055106:Genome-Wide Association Study / Q000379:methods; D006801:Humans; D008297:Male; D014029:Tobacco Use Disorder / Q000097:blood* / Q000208:ethnology / Q000235:genetics*; D044465:White People / Q000235:genetics*; D055815:Young Adult; D001741:Black or African American
chemical_list: D003367:Cotinine
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