# Deep sequencing of candidate genes identified 14 variants associated with smoking abstinence in an ethnically diverse sample

## TL;DR

This study found 14 genetic variants linked to quitting smoking success in a diverse group, offering new targets for personalized treatments.

## Contribution

The study identifies 14 novel genetic markers associated with smoking abstinence, including genes related to psychiatric disorders and cancer.

## Key findings

- 14 novel genetic variants were associated with smoking cessation success.
- Some variants were protective (e.g., CYP2B6, HTR3B), while others were linked to reduced cessation success (e.g., PARP15, SCL18A2).
- Network analysis highlighted pathways related to serotonin signaling, nicotine metabolism, and tumor suppression.

## Abstract

Despite the large public health toll of smoking, genetic studies of smoking cessation have been limited with few discoveries of risk or protective loci. We investigated common and rare variant associations with success in quitting smoking using a cohort from 8 randomized controlled trials involving 2231 participants and a total of 10,020 common and 24,147 rare variants. We identified 14 novel markers including 6 mapping to genes previously related to psychiatric and substance use disorders, 4 of which were protective (CYP2B6 (rs1175607105), HTR3B (rs1413172952; rs1204720503), rs80210037 on chr15), and 2 of which were associated with reduced cessation (PARP15 (rs2173763), SCL18A2 (rs363222)). The others mapped to areas associated with cancer including FOXP1 (rs1288980) and ZEB1 (rs7349). Network analysis identified significant canonical pathways for the serotonin receptor signaling pathway, nicotine and bupropion metabolism, and several related to tumor suppression. Two novel markers (rs6749438; rs6718083) on chr2 are flanked by genes associated with regulation of bodyweight. The identification of novel loci in this study can provide new targets of pharmacotherapy and inform efforts to develop personalized treatments based on genetic profiles.