Genetic ancestry as an effect modifier of naltrexone in smoking cessation among African Americans

Abstract

Objectives To determine if there were differential quit rates between AA and European Americans (EA) with the experimental treatment naltrexone, and examine the role of genetic ancestry on these outcomes among AAs. Methods Data from a previous randomized trial of 315 smokers to naltrexone vs. placebo were reanalyzed using West African (WA) genetic ancestry to define sub-populations. Logistic regression models were used to estimate treatment effects on early and end of treatment quit rates, by race and WA ancestry. Results Among EAs (n=136), naltrexone significantly increased quit rates at four weeks (62% vs. 43%, p=0.03) with directional, but not statistically significant effects at 12 weeks (30% vs. 18%, p=0.12). In contrast, among the AAs (n=95), quit rates did not differ between naltrexone and placebo groups at either interval (four weeks: 43% vs. 32%, p=0.27; 12 weeks: 22% vs. 18%, p=0.60). A median split was conducted in AAs for WA ancestry. Among AAs with low WA ancestry, quit rates were significantly higher with naltrexone compared with placebo (60% vs. 27%, p=0.03). There was no advantage in quit rates with naltrexone for the high WA ancestry group. Conclusions Naltrexone efficacy for smoking cessation varies across AA subjects with different levels of WA ancestry. These results suggest that genetic background may partially explain racial differences in drug response.

Reduction in Drinking was Associated With Improved Clinical Outcomes in Women With HIV Infection and Unhealthy Alcohol Use: Results From a Randomized Clinical Trial of Oral Naltrexone Versus Placebo

“…The fact that 94% of study participants were African American is different from most previous alcohol trials. Previous data suggest that naltrexone may not be as effective in African Americans than other racial groups (Bress et al., ; Ray and Oslin, ), and this could have contributed to the relative lack of an effect in our study.…”

Genetic Ancestry Analysis Reveals Misclassification of Commonly Used Cancer Cell Lines

“…Although the social and cultural influences of race on disease are undeniable, the role of genetics cannot be ignored. For example, an admixed individual with 20% EUR genetic ancestry may be at greater or lesser risk of certain diseases than an individual with 40% EUR genetic ancestry (56)(57)(58)(59)(60). In addition, the implications for pharmacogenomics exist as the nuances of drug effects or mechanisms may not be generalizable in the African American population due to high WA genetic variance (28,61).…”

West African Ancestry and Nocturnal Blood Pressure in African Americans: The Jackson Heart Study

“…Analyses were repeated using percentage of West African ancestry as a continuous variable normalized by the SD of the distribution, and by partitioning participants in 2 groups defined by the median split of the ancestry distribution. 29 For all analyses, missing covariate data were imputed with 10 data sets using chained equations. 37 The number and percentage of participants with missing data for each variable included in this analysis are reported in Supplementary Table 1.…”

“…24 The AIMS from the Nigerian parental population (i.e., HAPMAP YRI) are very useful proxies for West African Ancestry as these markers vary widely across continental populations but not within West and Central Africans. [25][26][27][28][29][30][31] A recent analysis of the genetic makeup of African Americans using more than 450,000 single-nucleotide polymorphisms found that African Americans are genetically derived mostly from West and West-Central African ancestral populations. 32 Moreover, an analysis of the 1000 Genomes Project sequence data found that the smallest genetic distance (Fixation index or F ST ) for African Americans is with the Yoruba from Nigeria.…”