A genetic association study of tobacco withdrawal endophenotypes in African Americans.

Abstract

Genome-wide association (GWA) genetic epidemiology research has identified several variants modestly associated with brief self-report smoking measures, predominately in European Americans. GWA research has not applied intensive laboratory-based measures of smoking endophenotypes in African Americans-a population with disproportionately low quit smoking rates and high tobacco-related disease risk. This genetic epidemiology study of non-Hispanic African Americans tested associations of 89 genetic variants identified in previous GWA research and exploratory GWAs with 24 laboratory-derived tobacco withdrawal endophenotypes. African American cigarette smokers (N = 528; ≥10 cig/day; 36.2% female) completed two counterbalanced visits following either 16-hr of tobacco deprivation or ad libitum smoking. At both visits, self-report and behavioral measures across six unique "sub-phenotype" domains within the tobacco withdrawal syndrome were assessed (Urge/Craving, Negative Affect, Low Positive Affect, Cognition, Hunger, and Motivation to Resume Smoking). Results of the candidate variant analysis found two significant small-magnitude associations. The rs11915747 alternate allele in the CAD2M gene region was associated with .09 larger deprivation-induced changes in reported impulsivity (0-4 scale). The rs2471711alternate allele in the AC097480.1/AC097480.2 gene region was associated with 0.26 lower deprivation-induced changes in confusion (0-4 scale). For both variants, associations were opposite in direction to previous research. Individual genetic variants may exert only weak influences on tobacco withdrawal in African Americans. Larger sample sizes of non-European ancestry individuals might be needed to investigate both known and novel loci that may be ancestry-specific. Public Significance StatementThis is the first study to integrate laboratory behavioral pharmacology with genetic epidemiology methods to study tobacco addiction endophenotypes in African Americans. No statistically robust or historically consistent associations of any genetic variants with 24 tobacco withdrawal endophenotypes assessed in this study were found. We did not find support for the notion that searching for specific genetic loci underlying intensively assessed tobacco withdrawal phenotypes in African Americans might lead to interventions that substantively reduce tobacco-related health disparities.

Nicotine deprivation amplifies attentional bias toward racial discrimination stimuli in African American adults who smoke cigarettes.

“…Participants were African American nontreatment seeking individuals who smoked cigarettes daily ( N = 344) recruited from Los Angeles, CA, United States during 2013−2017 via advertisements announcing a study on reasons people smoke cigarettes (Leventhal, Conti, et al, 2022). Inclusion criteria for the study were: (a) 18 years of age or older; (b) self-reported non-Hispanic African American; (c) daily cigarette smoking for ≥2 years; (d) currently smoking ≥10 cigarettes per day.…”

“…The present article reports results of a tack-on experiment to a parent study on individual differences in tobacco withdrawal phenotypes in African American individuals (Leventhal, Conti, et al, 2022). We added the racial discrimination Stroop measure into the parent study protocol midstream into data collection.…”