Deep Sequencing of Candidate Genes Identified 14 Variants Associated with Smoking Abstinence in an Ethnically Diverse Sample

Authors

Paul M Cinciripini
David W Wetter
Jian Wang
Robert Yu
George Kypriotakis
Tapsi Kumar
Jason D Robinson
Yong Cui
Charles E Green
Andrew W Bergen
Thomas R Kosten
Steven E Scherer
Sanjay Shete

Publication Date

3-16-2024

Journal

Scientific Reports

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.

Keywords

Smoking cessation, Candidate gene study, Single-nucleotide polymorphism, Rare variant, Sequencing

Comments

Supplementary Materials

PMID: 38493193