@article{7c9605acf52748bea29b2d435814ff05,
title = "Use of polygenic risk scores of nicotine metabolism in predicting smoking behaviors",
abstract = "Aim: This study tests whether polygenic risk scores (PRSs) for nicotine metabolism predict smoking behaviors in independent data. Materials & methods: Linear regression, logistic regression and survival analyses were used to analyze nicotine metabolism PRSs and nicotine metabolism, smoking quantity and smoking cessation. Results: Nicotine metabolism PRSs based on two genome wide association studies (GWAS) meta-analyses significantly predicted nicotine metabolism biomarkers (R2 range: 9.2-16%; minimum p = 7.6 × 10-8). The GWAS top hit variant rs56113850 significantly predicted nicotine metabolism biomarkers (R2 range: 14-17%; minimum p = 4.4 × 10-8). There was insufficient evidence for these PRSs predicting smoking quantity and smoking cessation. Conclusion: Results suggest that nicotine metabolism PRSs based on GWAS meta-analyses predict an individual's nicotine metabolism, so does use of the top hit variant. We anticipate that PRSs will enter clinical medicine, but additional research is needed to develop a more comprehensive genetic score to predict smoking behaviors.",
keywords = "CYP2A6, nicotine metabolism, polygenic risk scores, smoking cessation",
author = "Chen, {Li Shiun} and Hartz, {Sarah M.} and Baker, {Timothy B.} and Yinjiao Ma and {L Saccone}, Nancy and Bierut, {Laura J.}",
note = "Funding Information: MESA and the MESA SHARe project are conducted and supported by the National Heart, Lung, and Blood Institute (NHLBI) in collaboration with MESA investigators. Support for MESA is provided by contracts N01-HC95159, N01-HC-95160, N01-HC-95161, N01-HC-95162, N01-HC-95163, N01-HC-95164, N01-HC-95165, N01-HC95166, N01-HC-95167, N01-HC-95168, N01-HC-95169 and CTSA UL1-RR-024156. Funding for SHARe genotyping was provided by NHLBI Contract N02-HL-64278. Genotyping was performed at Affymetrix (CA, USA) and the Broad Institute of Harvard and MIT (Boston, Massachusetts, USA) using the Affymetric Genome-Wide Human SNP Array 6.0. Funding Information: The ARIC Study, sponsored by the National Heart, Lung and Blood Institute (NHLBI), is a longitudinal epidemiologic study to investigate the risk factors, medical care, natural history, and etiology of atherosclerosis and cardiovascular disease. Participants aged 45–64, at baseline, with and without atherosclerosis and cardiovascular disease were enrolled in Forsyth County, NC; Jackson, MS; the northwest suburbs of Minneapolis, MN; and Washington County, MD (USA) between 1987 and 1989 and followed-up yearly by telephone. A substudy, part of the Gene Environment Association Studies initiative (GENEVA, http://www.genevastudy.org), funded by the trans-NIH Genes, Environment and Health Initiative (GEI), contains genotype and phenotype data. The aim of this study is to identify and characterize factors that contribute to atherosclerosis and cardiovascular disease. Funding Information: This research was supported by R01DA036583, P30CA091842, U01HG004422 (LJB), R01DA038076, P30 CA091842-16S2, U19CA203654, K08DA030398, and KL2RR024994 (LSC), P50CA84724, K05CA139871, P50DA19706 (TBB), R01DA026911 (NLS). Funding Information: The Atherosclerosis Risk in Communities Study (ARIC; PI: E Boerwinkle) was obtained from dbGaP through study accession number phs000090. ARIC is carried out as a collaborative study supported by National Heart, Lung, and Blood Institute contracts N01-HC-55015, N01-HC-55016, N01-HC-55018, N01-HC-55019, N01-HC-55020, N01-HC-55021, N01-HC-55022, R01HL087641, R01HL59367 and R01HL086694; National Human Genome Research Institute contract U01HG004402; and NIH contract HHSN268200625226C. The authors thank the staff and participants of the ARIC study for their important contributions. Infrastructure was partly supported by Grant Number UL1RR025005, a component of the NIH and NIH Roadmap for Medical Research. Funding Information: The Collaborative Genetic Study of Nicotine Dependence (COGEND; PI: L Bierut) was supported by grant P01CA089392 from the National Cancer Institute. Genotyping services were provided by the Center for Inherited Disease Research (CIDR). CIDR is fully funded through a federal contract from the NIH to The Johns Hopkins University, contract number HHSN268200782096. Publisher Copyright: {\textcopyright} 2018 Future Medicine Ltd.",
year = "2018",
month = dec,
doi = "10.2217/pgs-2018-0081",
language = "English",
volume = "19",
pages = "1383--1394",
journal = "Pharmacogenomics",
issn = "1462-2416",
number = "18",
}