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. 2014 Apr 11;16(9):1224–1231. doi: 10.1093/ntr/ntu059

CHRNA5 Variant Predicts Smoking Cessation in Patients With Acute Myocardial Infarction

Li-Shiun Chen 1, Richard G Bach 2, Petra A Lenzini 3, John A Spertus 4, Laura Jean Bierut 1, Sharon Cresci 2,3,✉
PMCID: PMC4155476  PMID: 24727484

Abstract

Introduction:

While smoking is a major modifiable risk factor for secondary prevention of myocardial infarction (MI), active smoking is common among patients hospitalized with acute MI. Recent studies suggest that nicotinic receptor variants, and specifically the high-risk CHRNA5 rs16969968 A allele, are associated with cessation failure among noncardiac patients. This study investigates the association between CHRNA5 rs16969968 and smoking cessation in patients hospitalized with acute MI.

Methods:

Using data from the TRIUMPH study, we ascertained smoking status at the time of index hospitalization for acute MI and 1 year after hospitalization. After adjusting for age and sex, we used logistic regression to model the association between smoking cessation and CHRNA5 rs16969968.

Results:

At index admission, 752 Caucasian subjects were active smokers and 699 were former smokers. Among these ever-smokers, the A allele was associated with significantly decreased abstinence (45.0% abstinence for A allele carriers vs. 51.7% for GG homozygotes; odds ratio [OR] = 0.70, 95% confidence interval [CI] = 0.56–0.88, p = .0027). The A allele was also significantly associated with decreased abstinence at 1 year (69.1% abstinence for A allele carriers vs. 76.0% for GG homozygotes; OR = 0.70, 95% CI = 0.53–0.94, p = .0185).

Conclusions:

Among patients who have smoked and who are hospitalized with acute MI, the high-risk CHRNA5 allele was associated with lower likelihood of quitting before hospitalization and significantly less abstinence 1 year after hospitalization with MI. The CHRNA5 rs16969968 genotype may therefore identify patients who would benefit from aggressive, personalized smoking cessation intervention.

INTRODUCTION

Myocardial infarction (MI) remains a common cause of morbidity and mortality (Greenlund et al., 2004) and exacts a huge economic toll on society (CDC, 2007). Smoking is an important modifiable risk factor for MI (Rea et al., 2002). Smoking cessation is so important for both primary and secondary prevention of MI that efforts to support quitting have been established as a performance measure of hospital quality (Drozda et al., 2011; Wilson, Gibson, Willan, & Cook, 2000). Nonetheless, of patients hospitalized with acute MI who smoke, 50%–90% patients are found to be smoking at 6 months after MI, with or without treatment (Dawood et al., 2008; Joseph et al., 1996).

Both nicotine dependence and smoking cessation are heritable (Saccone et al., 2010; TAG, 2010; Uhl et al., 2008; Xian et al., 2003). Existing research indicates that variation in the nicotinic receptor genes, specifically, the region in chromosome 15q25 tagged by CHRNA5 rs16969968 and other linked variants, shows the strongest association with smoking quantity (number of cigarettes smoked per day [CPD]) and nicotine dependence in subjects of European ancestry. This finding was replicated in large-scale genome-wide association meta-analyses (Saccone et al., 2010; TAG, 2010). Variation in CHRNA5 has also been associated with smoking cessation, but this finding has been less consistent (Baker et al., 2009; Bergen et al., 2013; Chen, Baker, Piper, et al., 2012; Freathy et al., 2009; Munafo et al., 2011; Sarginson et al., 2011). We recently reported that, in a cohort of noncardiac patients, carriers of high-risk genetic markers for CHRNA5 rs16969968 had a significantly lower rate of cessation success and a favorable response to pharmacotherapy (number needed to treat = 4), while carriers of the low-risk genetic markers had a significantly higher rate of cessation success and did not benefit from medication (number needed to treat >1,000) (Chen, Baker, Piper, et al., 2012). These findings have recently been replicated in the large Pharmacogenetics of Nicotine Addiction Treatment (PNAT) consortium (Bergen et al., 2013).

Given the potential importance of these genetic markers in identifying patients who have difficulty quitting smoking, and in whom pharmacotherapy is particularly effective, we sought to test whether an association between CHRNA5 rs16969968 and smoking cessation would be found in post-MI patients, a population at particularly heightened health risks from continued smoking, with a self-perceived life-threatening condition that would be expected to provide strong motivation to stop smoking, and in whom there is a potential reluctance among clinicians/patients to use cessation medication due to potential health concerns of adverse effects with pharmacotherapy (May, Stocks, & Barton, 2008; Rigotti, Clair, Munafo, & Stead, 2012). Furthermore, because smoking relapses are known to be common in general (non–post-MI) populations (Fiore & Baker, 2011; Piper et al., 2009), we also examined whether smoking status at the time of admission would be associated with smoking status 1 year later. Finally, we wanted to quantify the effect size of the CHRNA5 rs16969968 variant in this relatively homogenous population (all post-MI) who are especially vulnerable to adverse consequences of continued smoking.

Using data from the Translational Research Investigating Underlying disparities in acute Myocardial infarction Patients’ Health Status (TRIUMPH) study, a prospective 24-center observational study of acute MI treatment and outcomes, we ascertained smoking status at index hospitalization and at 1 year. Our hypothesis was that CHRNA5 rs16969968 would be associated with smoking cessation in acute MI patients.

METHODS

Subjects

Between April 11, 2005 and December 31, 2008, 4,340 patients with acute MI, from 24U.S. hospitals, were prospectively enrolled into the TRIUMPH study, as previously described (Arnold et al., 2011; Cresci et al., 2011; Lanfear et al., 2011). MI patients were identified by an elevated troponin blood test and either diagnostic electrocardiogram changes or ischemic symptoms. A total of 2,979 TRIUMPH patients consented to genetic testing. In this analysis, we restricted our population to self-identified Caucasian patients who were self-reported current (i.e., active), former (i.e., quit ≥30 days before presentation), or never (i.e., never or <100 cigs in lifetime) smokers, yielding a final sample size of 1,451 ever-smokers and 543 never-smokers.

Every TRIUMPH patient was prospectively interviewed during hospitalization to ascertain their sociodemographic (including self-identified race), economic, and health status characteristics. Detailed chart abstractions were performed to obtain patients’ medical history, laboratory results, disease severity, and the processes of inpatient care, including prescription of first-line smoking cessation medications (nicotine patch, gum, lozenge, inhaler, nasal spray, bupropion, varenicline). TRIUMPH received Institutional Review Board approval at all participating sites and written informed consent was obtained from each participant.

Smoking behaviors were assessed for each subject during the index admission. Follow-up phone interviews were conducted 1 year later. About 95.0% of patients survived to 1 year (656 [93.8%] of baseline former smokers, 722 [96.0%] of baseline active smokers, and 517 [95.2%] of baseline never-smokers). Of survivors, 74% had 1-year smoking status follow-up information available. There were no clinically significant differences between patients who were and were not followed up at 1 year except that patients who received follow-up were slightly older than those not followed (59.3 [SD 10.9] years vs. 56.8 [SD 12.4] years, respectively; p = .0003). In the analysis of prospective smoking cessation (smoking status at 1-year follow-up), we included all subjects with smoking behavior information available at 1 year. As an additional analysis, we then restricted this population to individuals who were defined as active smokers at admission. Active smoking was defined with the response “I have smoked in the past 1 month” and former smoking was defined with the response “I stopped smoking more than a month ago.”

Genotyping

DNA was isolated and purified from whole blood using the Qiagen QIAamp DNA purification kit (Qiagen). Genotyping of CHRNA5 rs16969968 polymorphism was performed by pyrosequencing as previously described (Cresci et al., 2012; Marsh, King, Garsa, & McLeod, 2005). Pyrosequencing primers and conditions are available upon request. Pyrosequencing was performed using the PSQ HS 96A system with MA v2.0 software, as previously described (Cresci et al., 2012; Marsh et al., 2005). Data were automatically transferred from the PSQ HS 96A to a Microsoft Access database for permanent storage and merging with the clinical datasets through SAS v9.1. CHRNA5 rs16969968 genotype call rates were greater than 97% and did not deviate significantly from Hardy–Weinberg equilibrium. The minor allele frequency for rs1696968 was 0.31, consistent with the data for HapMap CEU (Durbin et al., 2010).

Statistical Analyses

Our primary analysis was the association of CHRNA5 rs16969968 and smoking cessation at index admission and at 1-year follow-up. Covariates included sex and age. Given that previous investigators have used both additive and dominant models when assessing associations with this variant (Chen, Baker, Grucza, et al., 2012; Chen, Baker, Piper, et al., 2012; Chen et al., 2009), for all genotype analyses we provide results separately for both additive and dominant models. Logistic regression was used to model the association between smoking cessation and the CHRNA5 rs16969968 variant.

RESULTS

Baseline characteristics of the cohort are shown in Table 1. Among 1,994 Caucasian TRIUMPH individuals admitted for acute MI who consented for genetic testing, 752 subjects were active smokers, 699 were former smokers, and 543 were never-smokers on admission. Demographic and clinical characteristics for ever-smokers (i.e., former + active) and never-smokers are given in Table 1A. Compared to never-smokers, the group of ever-smokers was younger and more likely to be male. In the group of ever-smokers, 19.9% had a history of previous MI, 21.7% had a history of percutaneous coronary intervention (PCI), 12.1% had a history of coronary artery bypass graft (CABG) surgery, 59.8% had hypertension, and 24.9% had diabetes, reflecting a population with a high prevalence of preexisting cardiovascular and metabolic risk factors.

Table 1.

Acute Myocardial Infarction Patient Characteristics at Baseline

A. Ever-smokers vs. never-smokers
Ever-smokers (N = 1,451) Never-smokers (N = 543) p value
Age, mean ± (SD) 58.7 (11.6) 62.15 (13) <.001
Sex, N (%)
 Female 358 (24.7) 200 (36.8) <.001
 Male 1093 (75.3) 343 (63.2)
Medical disorders, N (%)
 History of myocardial infarction 289 (19.9) 82 (15.1) .0139
 History of percutaneous coronary intervention 315 (21.7) 83 (15.3) .0014
 History of coronary artery bypass graft surgery 175 (12.1) 65 (12) .9561
 Hypertension 867 (59.8) 353 (65) .0320
 Diabetes 361 (24.9) 156 (28.7) .0808
B. Former vs. active smokers at index admission
Former smokers (N = 699) Active smokers (N = 752) p value
Age, mean ± (SD) 63.81 (11.4) 53.96 (9.6) <.001
Sex, N (%)
 Female 149 (21.3) 209 (27.8) .0043
 Male 550 (78.7) 330 (72.2)
BMI, kg/m2 29.8 (6.2) 28.9 (6) .0053
Average number of cigarettes smoked per day, in last 30 days, reported at baseline, mean ± (SD) NA 23.07 (32.7)
Cessation medication on arrival, N (%) 10 (1.4) 32 (4.3) .0013
Medical disorders, N (%)
 History of myocardial infarction 161 (23) 128 (17) .0042
 History of percutaneous coronary intervention 177 (25.3) 138 (18.4) .0013
 History of coronary artery bypass graft surgery 128 (18.3) 47 (6.3) <.001
 Hypertension 472 (67.5) 395 (52.5) <.001
 Diabetes 208 (29.8) 153 (20.3) <.001
 Dyslipidemia 406 (58.1) 332 (44.1) <.001
 Chronic kidney disease 50 (7.2) 13 (1.7) <.001
 History of congestive heart failure 59 (8.4) 20 (2.7) <.001
 History of CVA 36 (5.2) 19 (2.5) .0089
 History of TIA 26 (3.7) 11 (1.5) .0064
Cessation treatment on discharge, N (%)
 Medication (discharged on cessation med) 10 (1.4) 138 (18.4) <.001
 Counseling (instructed to stop smoking before discharge) 118 (16.9) 603 (80.2) <.001
 Medication or counseling 123 (17.6) 613 (81.5) <.001
C. Former vs. active smokers at 1-year follow-up
Former smokers (N = 715) Active smokers (N = 273) p value
Age, mean ± (SD)
Sex, N (%)
 Female 158 (22.1) 74 (27.1) .0968
 Male 557 (77.9) 199 (72.9)
Medical disorders, N (%)
 History of myocardial infarction 132 (18.5) 54 (19.8) .6350
 History of percutaneous coronary intervention 146 (20.4) 48 (17.6) .3154
 History of coronary artery bypass graft surgery 92 (12.9) 20 (7.3) .0140
 Hypertension 429 (60) 153 (56) .2584
 Diabetes 168 (23.5) 55 (20.1) .2600
 Cigarettes per day reported at baseline, mean ± (SD) 20.68 (41.5) 25.53 (38) .1846
Cessation treatment before discharge, N (%)
 Medication (discharged on cessation med) 52 (7.3) 47 (17.2) <.001
 Counseling (e.g., instructed to stop smoking) 250 (35) 231 (84.6) <.001
Cessation treatment at 1-year follow-up, N (%)
 Medication 13 (1.8) 7 (2.6) .4566
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Note. NA = nonapplicable.

Among ever-smokers, when former smokers were compared to current smokers, former smokers were more likely to be male (Table 1, 1B). The mean age of former smokers was almost 10 years older than active smokers and, perhaps related to this, former smokers had a significantly increased prevalence of comorbid conditions, including a history of MI, congestive heart failure, chronic kidney disease, cerebrovascular accident (CVA), dyslipidemia, transient ischemic attack (TIA), PCI, CABG surgery, hypertension, and diabetes. The difference between former and active smokers with respect to body mass index was statistically but not clinically significant (mean [SD]: 29.8 [6.2] vs. 28.9 [6.0], respectively). Although we did not have information regarding whether subjects had received instruction regarding smoking cessation prior to the index admission, only 1.4% of former smokers and 4.3% of active smokers were taking a cessation medication on admission. Among active smokers on admission, the majority (80.2%) received cessation counseling during hospitalization, but only a minority (18.4%) were discharged on cessation medication.

CHRNA5 rs16969968 Genotype Predicts Smoking Cessation at Index Admission

Baseline characteristics were compared between CHRNA5 rs16969968 GG homozygous subjects and CHRNA5 rs16969968 A allele carriers (Supplementary Table 1). There were no significant differences, including no difference in smoking cessation therapy on arrival or at discharge, between genotype groups. Of note, there was no significant difference between genotype groups in the number of CPD among active smokers.

The genetic effect of rs16969968 genotype on smoking cessation is shown in Figure 1. In logistic models adjusting for age and sex, the high-risk CHRNA5 rs16969968 A allele was significantly associated with decreased likelihood of abstinence at index admission (additive model: 47.2% abstinence for subjects with AA genotype, 44.4% for GA, 51.7% for GG; OR = 0.81, 95% CI = 0.68–0.97, p = .0201; dominant model: 45.0% abstinence for A allele carriers vs. 51.7% for GG homozygotes; OR = 0.70, 95% CI = 0.56–0.88, p = .0027; Figure 1).

Figure 1.

Figure 1.

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Genotype (rs16969968) predicts smoking cessation success at admission among ever-smokers (N = 1,451).

Abstinence at Time of Admission Predicts Abstinence at 1 Year

Abstinence at the time of admission was an important predictor of abstinence at 1 year (OR = 54.9, 95% CI = 30.6–98.5, p = 3.2×10−27; Figure 2). At 1-year follow-up, more than half (56.7%) of active smokers at baseline had persistent smoking. In contrast, only 2.7% of former smokers at baseline were active smokers (i.e., relapsed) at 1 year.

Figure 2.

Figure 2.

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Smoking status at time of admission predicts smoking status at 1-year follow-up. Active smokers at time of admission are more likely to relapse than former smokers at 1-year follow-up (N = 960). The association between baseline smoking status and smoking status at 1 year is significant, adjusted for age and sex (odds ratio [OR] = 54.9, 95% confidence interval [CI] = 30.6–98.5, p = 3.2×10−27).

CHRNA5 rs16969968 Genotype Predicts Smoking Cessation 1 Year After Admission

Smoking information at 1-year follow-up was available for 988 subjects (Table 1C). At 1 year, 273 subjects were active smokers and 715 were former smokers. There were no significant differences in sex, history of MI, revascularization, hypertension, or diabetes between active smokers and those who had quit smoking at 1 year after MI. The genetic effect of rs16969968 genotype on smoking cessation is shown in Figure 3. In logistic models adjusting for age and sex, the CHRNA5 rs16969968A allele was significantly associated with decreased likelihood of abstinence at 1 year (additive model: 67.3% abstinence for subjects with of AA genotype, 69.5% for GA, 76.0% for GG; OR = 0.77, 95% CI = 0.62–0.96, p = .0199; dominant model: 69.1% abstinence for A allele carriers vs. 76.0% for GG homozygotes; OR = 0.70, 95% CI = 0.53–0.94, p = .0185; Figure 3). If we restricted our analysis to the subjects who were active smokers at baseline (N = 477), we found 43.3% (N = 215) were abstinent from smoking at 1 year (and at all collected follow-up time points). Although the sample size is small in this subgroup, the association between variation in CHRNA5 rs16969968 and smoking cessation shows a consistent result in the same direction of effect for the A allele (additive model: OR = 0.87, 95% CI = 0.66–1.14, p = .31; dominant model: OR = 0.859, 95% CI = 0.60–1.24, p = .42).

Figure 3.

Figure 3.

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Genotype (rs16969968) and smoking cessation success at 1-year follow-up among ever-smokers (N = 988).

DISCUSSION

Our data demonstrate that among patients who had ever smoked and who were admitted to the hospital for acute MI, those carrying the high-risk CHRNA5 rs16969968 allele (AA or GA), as compared with those carrying only the low-risk allele (GG), were less likely to be abstinent from smoking at the time of index hospital admission and less likely to be abstinent at 1-year follow-up.

Patients presenting with acute MI often have multiple cardiovascular risk factors and smoking status is an important and potentially modifiable risk. Moreover, studies have shown that when a patient experiences an MI, the life-threatening nature of this event provides a strong motivation for quitting (Bock, Becker, Partridge, & Niaura, 2007). Even with this strong incentive to quit and commonly provided smoking cessation counseling, our data show that carriers of the high-risk CHRNA5 rs16969968 A allele are less likely than G allele carriers to successfully quit smoking.

CHRNA5 rs16969968 is located within a linkage disequilibrium block of highly correlated genetic variants across the gene cluster of CHRNA5-CHRNA3-CHRNB4 on chromosome 15. The CHRNA5 rs16969968 G>A variant results in a functional amino acid change (D398N) in the α5 nicotinic receptor subunit that leads to an altered receptor response to agonist binding (Bierut et al., 2008); the receptor containing asparagine at residue 398 (N398) exhibits a lower maximal response to nicotinic agonist compared with the receptor containing aspartic acid at residue 398 (D398). This reduced function may lead to an elevated risk for developing nicotine dependence and greater cessation difficulty (Bierut et al., 2008).

Existing research is controversial regarding the CHRNA5 rs16969968 variant and smoking cessation failure in non–post-MI populations. Some studies have observed an association between CHRNA5 rs16969968 A allele and smoking cessation failure (Baker et al., 2009; Chen, Baker, Piper, et al., 2012; Freathy et al., 2009; Munafo et al., 2011; Sarginson et al., 2011), while others failed to confirm this association (Breitling et al., 2010; Conti et al., 2008; Uhl et al., 2008). The large Tobacco and Genetics (TAG) meta-analysis consortium examined cessation (former vs. active smoker) in a general population and reported a modest (i.e., not meeting criteria for genome-wide significance) association with CHRNA5 rs16969968 (p < 1×10−4) (TAG, 2010). Our study is the first to establish the association of CHRNA5 rs16969968 with smoking cessation failure in patients with acute MI, a specific population that has a heightened risk from continued smoking and a significant benefit from successful quitting. Most importantly, this study establishes a consistent genetic association between CHRNA5 and the likelihood of successful abstinence at both time points—index admission and 1-year follow-up—in this high-risk population.

The current findings are also consistent with our recent report on the use of genetic markers in predicting patients’ smoking cessation success in a general population sample (Bergen et al., 2013; Chen, Baker, Piper, et al., 2012). Our previous investigation found that individuals with high-risk genetic markers appear more biologically predisposed to have difficulty quitting without treatment, but this risk may be ameliorated by effective pharmacological treatment. This current study extends these genetic findings into a post-MI cohort. Consistent with our previous findings, we show that patients with the high-risk allele (A) of CHRNA5 rs16969968 are less likely to quit smoking before hospitalization for MI and are less likely to quit smoking 1 year after discharge. However, due to the very low rate of smoking cessation pharmacotherapy use in TRIUMPH, we were unable to examine the pharmacogenetic interaction between CHRNA5 rs16969968 and pharmacologic treatment in this study.

Among non-MI patients, smoking relapses are frequent (Piper et al., 2009). Although smoking after MI significantly increases one’s health risk, the life-threatening nature of this event provides important motivation for quitting (Bock et al., 2007), and provision of smoking cessation counseling is a hospital quality performance metric (Hospital Quality Alliance [HQA] 2004–2007 measure build out table, 2008; Joint Commission on Accreditation of Healthcare Organization (JCAHO), 2007). A recent multicenter randomized trial in smokers hospitalized with acute MI reported that only one-third of patients were not actively smoking at 1-year follow-up (Eisenberg et al., 2013). Our findings in TRIUMPH support these observations as we found that only 43.3% of those actively smoking at the time of admission for acute MI had abstained from smoking at 1-year follow-up. However, the results of our analyses considerably extend these findings. To our knowledge, we are the first to report the high rate of continued abstinence in patients admitted for acute MI who had already quit smoking. In TRIUMPH, abstinence at the time of admission is a powerful predictor for abstinence at 1 year. We show that while smoking relapses are common in active smokers admitted for MI, among former smokers who have managed to quit smoking at least one month before admission, more than 97% remain abstinent at 1 year after discharge. This new finding regarding the natural course of smoking among MI patients may help inform the allocation of cessation treatment resources in this high-risk post-MI patient population.

In the current study, we also identified that use of smoking cessation medication in this group of active smokers with acute MI was uncommon on admission (4.3%), was infrequently prescribed at the time of discharge (18.4%), and was rarely prescribed at 1-year follow-up (2.6%). In contrast, most active smokers (80.2%) did receive smoking cessation counseling before discharge. This may reflect a reluctance of cardiologists to prescribe cessation medication for these patients at high risk for both smoking relapse and further cardiac events, perhaps related to concerns regarding the potential risks of cessation pharmacotherapy (May et al., 2008). The finding that more than half (56.7%) of patients who were actively smoking at the time of their MI failed to quit or relapsed within 1 year after hospitalization for acute MI despite counseling highlights the need to enhance application of existing smoking cessation treatments, such as cessation pharmacotherapy, for patients hospitalized for acute MI.

The results of this study should be interpreted in the context of several potential limitations. First, on admission, we did not have detailed smoking information on former smokers (e.g., the number of CPD they smoked when they were smoking). We did, however, have this information for active smokers at the time of admission and found no difference in daily cigarette consumption between genotype groups. We therefore have no indication that this variable is correlated with carrier status in our cohort. However, we acknowledge that the relationship of daily cigarette consumption to these genetic associations warrants further investigation. Second, the smoking reports in the TRIUMPH sample were not supported by biochemical confirmation. However, research shows that self-report is a valid indicator of current smoking, especially when there are no strong incentives to deceive (Society for Research on Nicotine and Tobacco Subcommittee on Biochemical Verification, 2002). Third, our previous investigation in non–post-MI subjects found that those individuals with the high-risk genetic variant of CHRNA5 rs16969968 appeared more biologically predisposed to have difficulty quitting without treatment, but that this risk was ameliorated by effective pharmacological treatment. We were underpowered to test the effect of pharmacotherapy in our current study because only a small portion of patients who had active smoking on admission received cessation medication at the time of discharge (18.4%) and at 1-year follow-up (2.6%). Finally, our current study only included subjects of European descent and, therefore, it is not clear whether our findings can be extrapolated to other racial groups.

While acknowledging the limitations of our study, it is notable that this work provides the first evidence of a high-risk genetic marker that predicts smoking cessation success at both baseline admission and 1-year follow-up in patients with acute MI—a population that is highly motivated to quit and in whom receipt of cessation counseling is highly prevalent and a hospital quality performance metric. These results build upon previous investigations of the genetics of smoking cessation and demonstrate a sustained genetic effect of the CHRNA5 rs16969968 variant up to 1 year after an acute major health event (surviving a hospitalization with MI). Furthermore, this work highlights the potential utility of CHRNA5 rs16969968 in predicting smoking cessation, shows the rare use of cessation medication in this very high-risk population, and underscores the potential to personalize cessation treatment by using genetic markers to identify higher risk patients.

SUPPLEMENTARY MATERIAL

Supplementary Table 1 can be found online at http://www.ntr.oxfordjournals.org

FUNDING

This work and SC’s effort were supported in part by the National Institutes of Health (R01 NR013396 to SC) and the Longer Life Foundation. L-SC’s effort was supported in part by the National Institute on Drug Abuse (K08 DA030398 to L-SC). LJB’s effort was supported in part by the National Cancer Institute (P01 CA089392 to LJB), National Institute on Drug Abuse (K02 DA021237 to LJB), and the National Human Genome Research Institute (U01 HG004422 to LJB). TRIUMPH was sponsored by the National Institutes of Health: Washington University School of Medicine Specialized Centers of Clinically Oriented Research (SCCOR) Grant P50 HL077113.

DECLARATION OF INTERESTS

LJB is listed as an inventor on issued U.S. patent 8,080,371, “Markers for Addiction,” covering the use of certain single-nucleotide polymorphism in determining the diagnosis, prognosis, and treatment of addiction.

Supplementary Material

Supplementary Data
supp_16_9_1224__index.html (837B, html)

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supp_ntu059_Supplemental_Table_1.pdf (301.4KB, pdf)

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